On December 9, 2024 Protara Therapeutics, Inc. (Nasdaq: TARA) ("Protara"), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported that it has commenced an underwritten public offering of shares of its common stock or, in lieu of issuing common stock to certain investors, pre-funded warrants to purchase shares of its common stock (Press release, Protara Therapeutics, DEC 9, 2024, View Source [SID1234648887]). All of the shares of common stock and pre-funded warrants to be sold in the proposed offering will be offered by Protara. In addition, Protara expects to grant the underwriters a 30-day option to purchase additional shares of common stock at the public offering price, less underwriting discounts and commissions. The proposed offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or the actual size or terms of the offering. Protara intends to use the net proceeds received from the offering to fund the clinical development of TARA-002, as well as the development of other clinical programs. Protara may also use the net proceeds from the offering for working capital and other general corporate purposes.

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TD Cowen, Cantor, LifeSci Capital, Oppenheimer & Co. and Scotiabank are acting as joint book-running managers of the proposed offering.

The shares of common stock and the pre-funded warrants will be issued pursuant to a shelf registration statement on Form S-3 (File No. 333-275290) that was declared effective on November 14, 2023 by the U.S. Securities and Exchange Commission (the "SEC"). The offering is being made only by means of a preliminary prospectus supplement and the accompanying prospectus. A preliminary prospectus supplement and the accompany prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement and the accompany prospectus relating to the offering, when available, may be obtained from the offices of TD Securities (USA) LLC, 1 Vanderbilt Avenue, New York, New York 10017, by email at [email protected] or by telephone at (855) 495-9846; Cantor Fitzgerald & Co., 110 East 59th Street, 6th Floor, New York, New York 10022, Attention: Capital Markets, or by email at [email protected]; or LifeSci Capital LLC, 1700 Broadway, 40th Floor, New York, New York 10019, or by email at [email protected].

Before investing in the offering, interested parties should read the preliminary prospectus supplement and related prospectus for this offering, the documents incorporated by reference therein and the other documents Protara has filed with the Securities and Exchange Commission. The final terms of the offering will be disclosed in a final prospectus supplement to be filed with the Securities and Exchange Commission.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any of these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the applicable securities laws of such state or jurisdiction.

On December 08, 2024 AstraZeneca reported the positive results from the AMPLIFY Phase III trial showed CALQUENCE (acalabrutinib) in combination with venetoclax demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to standard-of-care chemoimmunotherapy in previously untreated adult patients with chronic lymphocytic leukemia (CLL) (Press release, AstraZeneca, DEC 8, 2024, View Source [SID1234648886]).

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These results will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2024 Annual Meeting in San Diego, CA.

At a median follow up of 41 months, results showed CALQUENCE plus venetoclax reduced the risk of disease progression or death by 35% compared to standard-of-care chemoimmunotherapy (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.49-0.87; p=0.0038). CALQUENCE plus venetoclax with obinutuzumab demonstrated a 58% reduction in the risk of disease progression or death compared to standard-of-care chemoimmunotherapy (HR 0.42; 95% CI 0.30-0.59; p<0.0001). Median PFS was not reached for either experimental arm versus median PFS of 47.6 months for chemoimmunotherapy.

Interim overall survival (OS) data demonstrated a favorable trend which was nominally statistically significant for CALQUENCE plus venetoclax (HR 0.33; 95% CI 0.18-0.56; p<0.0001), however the OS data were immature at the time of this analysis and the trial will continue to assess OS as a key secondary endpoint.

Jennifer R. Brown, MD, PhD, Director of the CLL Center of the Division of Hematologic Malignancies, Dana-Farber Cancer Institute, and the Worthington and Margaret Collette Professor of Medicine at Harvard Medical School, and principal investigator of the trial, said: "Chronic lymphocytic leukemia is considered an incurable cancer and patients live with the disease and the long-term effects of their treatments for many years. The AMPLIFY results show the promise of a new all-oral fixed-duration therapy approach which would allow patients to take breaks from treatment, reducing the risk of long-term adverse events and drug resistance."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "Based on these impressive data from the AMPLIFY trial, CALQUENCE is the only second-generation BTK inhibitor to demonstrate efficacy in the front-line treatment of patients with chronic lymphocytic leukemia as both a treat-to-progression and a fixed-duration approach. This advance is an important development for patients and their physicians who seek new options and more flexibility in managing this disease in the long term."

Both investigational arms demonstrated durable responses, with estimated 36-month PFS rates of 76.5% for CALQUENCE plus venetoclax and 83.1% with the addition of obinutuzumab compared to 66.5% for chemoimmunotherapy. Patients also demonstrated a robust response in both investigational arms with an overall response rate (ORR) of 92.8% for CALQUENCE plus venetoclax and 92.7% with the addition of obinutuzumab, compared to 75.2% for chemoimmunotherapy.

Summary of Results: AMPLIFY

CALQUENCE plus venetoclax

CALQUENCE plus venetoclax and obinutuzumab

Control arm

Patient population (n)

291

286

290

Median PFS

(months)

NR

NR

47.6

PFS HR vs. control

(95% CI)

0.65

p=0.0038

0.42

p<0.0001

Reference

36-month PFS rate

76.5%

83.1%

66.5%

ORR (95% CI)

92.8% (89.4-95.4)

p<0.0001

92.7% (89.2-95.3)

p<0.0001

75.2% (70.0-79.9)

OS HR vs. control (95% CI)

0.33 (0.18-0.56)

p<0.0001

0.76 (0.49-1.18)

p=0.2224

Reference

NR=Not reached

Control arm = Investigator’s choice of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab

The safety and tolerability of CALQUENCE was consistent with its known safety profile, and no new safety signals were identified. Grade 3 or higher adverse events (AEs) occurred in 53.6% of patients treated with CALQUENCE plus venetoclax, 69.4% of patients treated with CALQUENCE plus venetoclax with obinutuzumab and 60.6% for patients treated with standard-of-care chemoimmunotherapy. The most common Grade 3 or higher AE was neutropenia across all arms, seen in 26.8%, 35.2% and 32.4% of patients respectively. There were over twice as many COVID-19 related deaths in the CALQUENCE plus venetoclax with obinutuzumab arm compared with the CALQUENCE plus venetoclax arm.

Notably, low rates of tumor lysis syndrome (TLS) were observed in both CALQUENCE arms with events of any grade seen in 0.3% of patients treated with CALQUENCE plus venetoclax and 0.4% with the addition of obinutuzumab, compared to 3.1% for patients treated with chemoimmunotherapy. No cases of clinical TLS were observed across CALQUENCE treatment arms.

CALQUENCE has been used to treat more than 85,000 patients worldwide1 and is approved for the treatment of CLL and small lymphocytic lymphoma (SLL) in the US and Japan, approved for CLL in the EU and many other countries worldwide and approved in China for relapsed or refractory CLL and SLL.

INDICATION AND USAGE

CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE (acalabrutinib) tablets

Serious and Opportunistic Infections

Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE.

Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 19% of 1029 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (11% of all patients, including pneumonia in 6%). These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 1.9% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jirovecii pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML). Consider prophylaxis in patients who are at increased risk for opportunistic infections. Monitor patients for signs and symptoms of infection and treat promptly.

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematologic malignancies treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 3.0% of patients, with fatal hemorrhage occurring in 0.1% of 1029 patients exposed to CALQUENCE in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 22% of patients.

Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 2.7% of patients taking CALQUENCE without antithrombotic agents and 3.6% of patients taking CALQUENCE with antithrombotic agents. Consider the risks and benefits of antithrombotic agents when co-administered with CALQUENCE. Monitor patients for signs of bleeding.

Consider the benefit-risk of withholding CALQUENCE for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (23%), anemia (8%), thrombocytopenia (7%), and lymphopenia (7%), developed in patients with hematologic malignancies treated with CALQUENCE. Grade 4 neutropenia developed in 12% of patients. Monitor complete blood counts regularly during treatment. Interrupt treatment, reduce the dose, or discontinue treatment as warranted.

Second Primary Malignancies

Second primary malignancies, including skin cancers and other solid tumors, occurred in 12% of 1029 patients exposed to CALQUENCE in clinical trials. The most frequent second primary malignancy was skin cancer, reported in 6% of patients. Monitor patients for skin cancers and advise protection from sun exposure.

Cardiac Arrhythmias

Serious cardiac arrhythmias have occurred in patients treated with CALQUENCE. Grade 3 atrial fibrillation or flutter occurred in 1.1% of 1029 patients treated with CALQUENCE, with all grades of atrial fibrillation or flutter reported in 4.1% of all patients. Grade 3 or higher ventricular arrhythmia events were reported in 0.9% of patients. The risk may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection. Monitor for symptoms of arrhythmia (eg, palpitations, dizziness, syncope, dyspnea) and manage as appropriate.

Hepatotoxicity, Including Drug-Induced Liver Injury

Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including CALQUENCE.

Evaluate bilirubin and transaminases at baseline and throughout treatment with CALQUENCE. For patients who develop abnormal liver tests after CALQUENCE, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold CALQUENCE. Upon confirmation of DILI, discontinue CALQUENCE.

ADVERSE REACTIONS

The most common adverse reactions (≥30%) of any grade in patients with CLL were anemia,* neutropenia,* thrombocytopenia,* headache, upper respiratory tract infection, and diarrhea.

*Treatment-emergent decreases (all grades) of hemoglobin, platelets, and neutrophils were based on laboratory measurements and adverse reactions.

In patients with previously untreated CLL exposed to CALQUENCE, fatal adverse reactions that occurred in the absence of disease progression and with onset within 30 days of the last study treatment were reported in 2% for each treatment arm, most often from infection. Serious adverse reactions were reported in 39% of patients in the CALQUENCE plus obinutuzumab arm and 32% in the CALQUENCE monotherapy arm, most often due to events of pneumonia (7% and 2.8%, respectively).

Adverse reactions led to CALQUENCE dose reduction in 7% and 4% of patients in the CALQUENCE plus obinutuzumab arm (N=178) and CALQUENCE monotherapy arm (N=179), respectively. Adverse events led to discontinuation in 11% and 10% of patients, respectively. Increases in creatinine to 1.5 to 3 times the upper limit of normal (ULN) occurred in 3.9% and 2.8% of patients in the CALQUENCE combination arm and monotherapy arm, respectively.

In patients with relapsed/refractory CLL exposed to CALQUENCE, serious adverse reactions occurred in 29% of patients. Serious adverse reactions in >5% of patients who received CALQUENCE included lower respiratory tract infection (6%). Fatal adverse reactions within 30 days of the last dose of CALQUENCE occurred in 2.6% of patients, including from second primary malignancies and infection.

Adverse reactions led to CALQUENCE dose reduction in 3.9% of patients (N=154), dose interruptions in 34% of patients, most often due to respiratory tract infections followed by neutropenia, and discontinuation in 10% of patients, most frequently due to second primary malignancies followed by infection. Increases in creatinine to 1.5 to 3 times ULN occurred in 1.3% of patients who received CALQUENCE.

DRUG INTERACTIONS

Strong CYP3A Inhibitors: Avoid co-administration of CALQUENCE with a strong CYP3A inhibitor. If these inhibitors will be used short-term, interrupt CALQUENCE. After discontinuation of strong CYP3A inhibitor for at least 24 hours, resume previous dosage of CALQUENCE.

Moderate CYP3A Inhibitors: Reduce the dosage of CALQUENCE to 100 mg once daily when co-administered with a moderate CYP3A inhibitor.

Strong CYP3A Inducers: Avoid co-administration of CALQUENCE with a strong CYP3A inducer. If co-administration is unavoidable, increase the dosage of CALQUENCE to 200 mg approximately every 12 hours.

SPECIFIC POPULATIONS

Based on findings in animals, CALQUENCE may cause fetal harm and dystocia when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. Advise pregnant women of the potential risk to a fetus.

Pregnancy testing is recommended for females of reproductive potential prior to initiating CALQUENCE therapy. Advise female patients of reproductive potential to use effective contraception during treatment with CALQUENCE and for 1 week following the last dose of CALQUENCE.

It is not known if CALQUENCE is present in human milk. Advise lactating women not to breastfeed while taking CALQUENCE and for 2 weeks after the last dose.

Avoid use of CALQUENCE in patients with severe hepatic impairment (Child-Pugh class C). No dosage adjustment of CALQUENCE is recommended in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.

Please see full Prescribing Information, including Patient Information.

Notes

Chronic Lymphocytic Leukemia (CLL)

CLL is the most prevalent type of leukemia in adults, with over 100,000 new cases globally in 2019.2 Although some people with CLL may not experience any symptoms at diagnosis, others may experience symptoms, such as weakness, fatigue, weight loss, chills, fever, night sweats, swollen lymph nodes and abdominal pain.3 In CLL, there is an accumulation of abnormal lymphocytes within the blood, bone marrow and lymph nodes. As the number of abnormal cells increases, there is less room within the marrow for the production of normal white blood cells, red blood cells and platelets.4 This could result in infection, anemia and bleeding. B-cell receptor signaling through BTK is one of the essential growth pathways for CLL.

AMPLIFY

AMPLIFY is a randomized, global, multi-center, open-label Phase III trial evaluating the efficacy and safety of CALQUENCE in combination with venetoclax with and without obinutuzumab compared to investigator’s choice of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) in adult patients with previously untreated CLL without del(17p) or TP53 mutation.5 Patients were randomized 1:1:1 to receive either CALQUENCE plus venetoclax, CALQUENCE plus venetoclax with obinutuzumab for a fixed duration or standard-of-care chemoimmunotherapy.5 Both the CALQUENCE containing arms were administered for a fixed duration of 14 cycles (each 28 days), and the standard-of-care chemoimmunotherapy was for 6 cycles.5

The primary endpoint is PFS in the CALQUENCE and venetoclax arm as assessed by an Independent Review Committee and PFS in the CALQUENCE plus venetoclax with obinutuzumab is a key secondary endpoint. Other key secondary endpoints include OS and undetectable measurable residual disease.5 The trial includes 27 countries across North and South America, Europe, Asia and Oceania.5

The AMPLIFY trial enrolled patients from 2019 to 2021, continuing through the COVID-19 pandemic.5 Patients with blood cancer remain at a disproportionately high risk of severe outcomes from COVID-19, including hospitalization and death compared to the general population.6

CALQUENCE

CALQUENCE (acalabrutinib) is a second-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). CALQUENCE binds covalently to BTK, thereby inhibiting its activity.7 In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.

CALQUENCE is also approved in the US, China and several other countries for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. CALQUENCE is not currently approved for the treatment of MCL in Japan or the EU.

As part of an extensive clinical development program, CALQUENCE is currently being evaluated as a single treatment and in combination with standard-of-care chemoimmunotherapy for patients with multiple B-cell blood cancers, including CLL, MCL and diffuse large B-cell lymphoma.

On December 08, 2024 Be Biopharma, Inc. ("Be Bio"), a clinical-stage company pioneering engineered B Cell Medicines (BCMs), reported two key updates at the 66th ASH (Free ASH Whitepaper) Annual Meeting in San Diego, CA (Press release, Be Biopharma, DEC 8, 2024, View Source [SID1234648885]). These updates include a Trial in Progress poster detailing the BeCoMe-9 clinical trial and an oral presentation highlighting the potential of Be Bio’s BCM platform to create innovative programs with best-in-class profiles.

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"Our BCM platform offers transformative potential to improve the delivery of therapeutic biologics across a wide spectrum of genetic diseases, cancers and other therapeutic areas."

The Trial in Progress poster highlights the design of Be Bio’s BeCoMe-9 clinical trial, evaluating BE-101 in patients with Hemophilia B. BE-101, the Company’s lead clinical program, is an autologous BCM therapy engineered to express human factor IX (hFIX). This innovative therapy aims to offer a transformative new therapeutic option by delivering sustained hFIX levels, addressing the needs in patients with hemophilia B, a bleeding disorder affecting approximately 40,000 people globally. Despite advancements, many people living with hemophilia B continue to experience regular bleeding events that can lead to chronic pain and irreversible joint damage. BE-101 is designed to provide long-lasting FIX protection using the patient’s own B cells, with the flexibility to be titratable and redosable as needed. The BeCoMe-9 first-in-human Phase 1/2 trial is actively enrolling patients and aims to achieve clinical proof of concept for both BE-101 and the BCM platform. BE-101 has been granted Orphan Drug and Fast Track Designations by the FDA, underscoring its potential to address important unmet needs.

"This year marks a pivotal milestone for Be Bio as we have transitioned into a clinical stage company, advancing our groundbreaking science into lead programs that aim to deliver new therapeutic options for patients in need," said Joanne Smith-Farrell, PhD, Chief Executive Officer of Be Bio. "In 2025, the BeCoMe-9 trial is poised to generate clinical proof of concept for BE-101, advancing this critical program for patients while demonstrating the transformative potential of our B Cell Medicine platform."

The BeCoMe-9 study is designed to evaluate the safety and clinical activity of a single IV dose of BE-101 in adults with moderately severe or severe Hemophilia B. The study consists of two parts. Part 1 employs an ascending-dose design, enabling the stepwise evaluation of increasing dose levels to determine a safe and effective dose. Once this dose is identified, Part 2 will add a cohort to confirm and further characterize the safety and activity of BE-101 at the selected dose along with a cohort to include adolescents. Details of the poster presentation are as follows:

Abstract Title: BeCoMe–9: A Phase 1/2 Dose Escalation and Expansion Study of BE-101 for the Treatment of Adults with Moderately Severe or Severe Hemophilia B
Session Name: 322. Hemophilia A and B: Clinical and Epidemiological: Poster II
Publication Number: 2593.1
Date: Sunday, December 8, 2024
Time: 6:00 PM – 8:00 PM PT
Session Room: San Diego Convention Center, Halls G-H

Be Bio’s oral presentation on December 7 highlighted the versatility of BCMs in delivering therapeutic biologics for diverse patient populations and diseases. BCMs are designed to produce constant levels of therapeutic proteins in a durable, redosable, and titratable manner, all without the need for preconditioning. The presentation highlighted data from the Company’s two lead candidates, BE-101, a clinical-stage BCM engineered to express hFIX as a potential new treatment for Hemophilia B, and BE-102, a development candidate engineered to express tissue nonspecific alkaline phosphatase (ALP) as a potential treatment option for hypophosphatasia (HPP). The presentation also included data from a BCM prototype engineered to express an anti-CD3:CD19 scFv bispecific T cell engager, which demonstrated a significant reduction in tumor burden in a patient-derived xenograft model of acute lymphoblastic leukemia.

"These data reinforce the capabilities of our versatile B cell engineering platform to develop novel BCMs that express therapeutically relevant proteins," said Rick Morgan, Ph.D., Chief Scientific Officer, Be Biopharma. "Our BCM platform offers transformative potential to improve the delivery of therapeutic biologics across a wide spectrum of genetic diseases, cancers and other therapeutic areas."

About Engineered B Cell Medicines – A New Class of Cellular Medicines
The B cell is a powerful cell that produces thousands of proteins per cell per second at constant levels, over decades. Precision genome editing can now be used to engineer B Cells that produce therapeutic proteins of interest, driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs) – with the potential to be durable, allogeneic, redosable, titratable and administered without pre-conditioning. The promise of BCMs could transform therapeutic biologics with broad application — across diverse protein classes, patient populations and therapeutic areas.

About BE-101
BE-101 is a first-in-class engineered B Cell Medicine (BCM) designed to treat Hemophilia B by inserting the human Factor IX (FIX) gene into primary human B cells, enabling continuous expression of active FIX. BE-101 offers the potential for sustained therapeutic FIX activity levels with a single infusion, with the flexibility to be titrated and/or re-dosed, and without the need for preconditioning. By maintaining sustained and constant therapeutic FIX activity levels while reducing dosing frequency required by current FIX replacement regimens, BE-101 could alleviate the considerable infusion burden faced by people with Hemophilia B while potentially lowering annualized bleeding rates and FIX usage. The US FDA cleared the BE-101 IND in May of 2024, and has granted the program Fast Track and Orphan Designations. The Phase 1/2 BeCoMe-9 Trial is open for enrollment and further details of the trial can be found at www.clinicaltrials.gov under NCT identifier: NCT06611436.

On December 08, 2024 Arcellx, Inc. (NASDAQ: ACLX), a biotechnology company reimagining cell therapy through the development of innovative immunotherapies for patients with cancer and other incurable diseases, reported new positive data from its Phase 2 pivotal iMMagine-1 study of anitocabtagene autoleucel (anito-cel), in patients with relapsed or refractory multiple myeloma (RRMM) (Press release, Arcellx, DEC 8, 2024, View Source [SID1234648884]). These data will be presented during an oral presentation at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on Monday, December 9, 2024 at 5:30 p.m. PT. Anito-cel is partnered with Kite, a Gilead Company. Additional presentations during ASH (Free ASH Whitepaper) are also noted below.

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The Phase 2 iMMagine-1 data are from an October 31, 2024 data cutoff date, with a median follow-up of 9.5 months for the efficacy evaluable population. At the time of the data cut, 86 patients were evaluable for efficacy based on a follow-up of at least two months after treatment with anito-cel, and 98 patients were evaluable for safety based on a follow-up of at least one month after treatment with anito-cel. All patients received a single infusion of anito-cel (target dose of 115×106 CAR+ viable T cells). In the safety evaluable population, 85 of 98 patients (87%) were triple refractory, and 41 of 98 patients (42%) were penta refractory. Patients received a median of four prior lines of therapy, with 45 of 98 patients (46%) having received three prior lines.

Overall response rate (ORR) was 97% (83/86) with a complete response/stringent complete response (CR/sCR) rate of 62% (53/86) and a very good partial response or higher (>VGPR) rate of 81% (70/86), per International Myeloma Working Group (IMWG) criteria as investigator-assessed. Of those evaluable for minimal residual disease (MRD) testing, 93.1% (54/58) achieved MRD negativity at a minimum of 10-5 sensitivity. Median progression-free survival (mPFS) and overall survival (OS) were not reached; 6-month PFS and OS rates were 93.3% and 96.5%, respectively, and 12-month PFS and OS rates were 78.5% and 96.5%, respectively.

No delayed or non-ICANS neurotoxicities, including no Parkinsonism, no cranial nerve palsies, and no Guillain-Barré syndrome, have been observed to date in more than 150 patients dosed with anito-cel. Of the safety evaluable population, 86% (84/98) had Grade ≤1 cytokine release syndrome (CRS), including 17% of patients with no CRS. Among patients experiencing CRS, the median onset was four days (range: 1-17 days). Eight percent of patients (8/98) were treated as outpatient. Ninety-one percent (89/98) of patients had no ICANS. Any Grade ICANS was observed in 9 patients (9%; Gr3 1%), with all cases resolved without sequelae. Three deaths occurred due to treatment-emergent adverse events (TEAEs) (related or unrelated to anito-cel: retroperitoneal hemorrhage, CRS, and fungal infection). No additional treatment or therapy-related deaths or Grade ≥3 CRS or ICANs events have occurred to date. Cytopenias were the most common Grade ≥3 TEAEs; 53 patients (54%) had Grade ≥3 neutropenia, 20 (20%) had Grade ≥3 thrombocytopenia, and 22 (22%) had Grade ≥3 anemia.

Conclusions

Preliminary results from the Phase 2 iMMagine-1 study demonstrate deep and durable responses with a predictable and manageable safety profile in a high-risk fourth-line or higher (4L+) RRMM population, including triple- and penta-class refractory disease. Notably, no delayed or non-ICANS neurotoxicities, including no Parkinsonism, no cranial nerve palsies, and no Guillain-Barré syndrome, have been observed with anito-cel to date.

Ciara Freeman, M.D., Ph.D., Assistant Member, Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center said, "The data from the iMMagine-1 study demonstrate that this is a highly active product with impressive depth of responses achieved in patients with relapsed or refractory multiple myeloma. As a physician who treats many patients both inpatient and in the outpatient setting, the emerging safety profile of anito-cel is encouraging, in particular the absence of any delayed neurotoxicities reported to date. We are excited to begin enrolling patients in the iMMagine-3 study and in the near future having anito-cel as an approved treatment option."

Arcellx’s Chairman and Chief Executive Officer, Rami Elghandour, said, "It’s exciting to reach this momentous milestone in our pivotal study and present these compelling data. These data, along with the data from our Phase 1 study, which demonstrated a 30.2-month median PFS and zero cases of delayed neurotoxicity or other non-ICANS neurotoxicity with all patients having more than two years of follow-up, continue to support our conviction that anito-cel has the potential to be a best-in-class treatment option for patients with RRMM. Additionally, with iMMagine-3 underway in earlier lines in a patient population representing an unmet clinical need, we expect to further position anito-cel as a differentiated CAR-T treatment option for RRMM. Separately, this year is Arcellx’s 10th anniversary! I’m grateful for the incredible people who make up the fabric of Arcellx and have poured themselves into developing this life-saving therapy for the patients most in need. And I’m proud of how we’ve done it, leaning into our diversity as a cornerstone of our culture, which underpins our success. I especially appreciate the partnership, collaboration, and trust of the Phase 1 and iMMagine-1 clinicians who helped enroll patients in these studies and allowed us to demonstrate the potential benefit of anito-cel. I’m also grateful to those who believed in us, our founding investors and scientists, our investors who helped us go public nearly three years ago in a challenging market, and those who have joined us along the way. To our colleagues at Kite, we thank you for your partnership. To everyone who’s been part of this incredible journey, thank you! We’re just getting started!"

ASH Presentation Details

Phase 2 Registrational Study of Anitocabtagene Autoleucel for the Treatment of Patients with Relapsed and/or Refractory Multiple Myeloma: Preliminary Results From the iMMagine-1 Trial (abstract #1031)

Speaker: Ciara Freeman, M.D., Ph.D., H. Lee Moffitt Cancer Center
Session Name: 655. Multiple Myeloma: Cellular Therapies: Unleashing Cell Therapies Against Myeloma
Session Date: Monday, December 9, 2024
Session Time: 4:30 p.m. – 6:00 p.m. PT
Presentation Time: 5:30 p.m. PT
Location: Marriott Marquis San Diego Marina, Pacific Ballroom Salons 24-26
Publication Number: 1031
Submission ID: 198499

Phase 1 Study of Anitocabtagene Autoleucel for the Treatment of Patients With Relapsed and/or Refractory Multiple Myeloma (RRMM) (abstract #4825)

Speaker: Michael R. Bishop, M.D., The University of Chicago
Session Name: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities
Session Date: Monday, December 9, 2024
Presentation Time: 6:00 p.m. – 8:00 p.m. PT
Location: San Diego Convention Center, Halls G-H
Publication Number: 4825
Submission ID: 201080

Health Related Quality of Life (HRQoL) in Relapsed/Refractory Multiple Myeloma (RRMM): A Systematic Literature Review (SLR) and Meta-Analysis (abstract #4721)

Speaker: Rahul Banerjee, M.D., Fred Hutchinson Cancer Center
Session Name: 653. Multiple Myeloma: Clinical and Epidemiological: Poster III
Session Date: Monday, December 9, 2024
Presentation Time: 6:00 p.m. – 8:00 p.m. PT
Location: San Diego Convention Center, Halls G-H

Treatment Patterns and Outcomes in Triple-Class Exposed Patients with Relapsed and Refractory Multiple Myeloma: Findings from the Flatiron Database (abstract #6962)

This abstract will be published in a supplemental issue of Blood in November 2024.

Webcast Event (New Start Time):

Arcellx will host a live webcast event with an expert panel of clinicians to discuss the clinical results on Monday, December 9, 2024 at 8 p.m. PT. The event will be accessible from the Investors section of the Company’s website at ir.arcellx.com. A webcast replay will be archived and available for 30 days following the event.

About Multiple Myeloma

Multiple Myeloma (MM) is a type of hematological cancer in which diseased plasma cells proliferate and accumulate in the bone marrow, crowding out healthy blood cells and causing bone lesions, loss of bone density, and bone fractures. These abnormal plasma cells also produce excessive quantities of an abnormal immunoglobulin fragment, called a myeloma protein (M protein), causing kidney damage and impairing the patient’s immune function. Multiple myeloma is the third most common hematological malignancy in the United States and Europe, representing approximately 10% of all hematological cancer cases and 20% of deaths due to hematological malignancies. The median age of patients at diagnosis is 69 years with one-third of patients diagnosed at an age of at least 75 years. Because MM tends to afflict patients at an advanced stage of life, patients often have multiple co-morbidities and toxicities that can quickly escalate and become life-endangering.

About Anitocabtagene Autoleucel (anito-cel)

Anitocabtagene autoleucel (anito-cel, previously ddBCMA) is the first BCMA-directed CAR T-cell therapy to be investigated in multiple myeloma that utilizes Arcellx’s novel and compact binder known as the D-Domain. The small, stable D-Domain binder enables high CAR expression without tonic signaling and is designed to quickly release from the BCMA target. This combination may allow for the effective elimination of multiple myeloma cells without severe immunotoxicity. Anito-cel has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy Designations by the U.S. Food and Drug Administration.

About iMMagine-3, A Global Phase 3 Randomized Controlled Clinical Study

iMMagine-3 is a global Phase 3 randomized controlled study designed to compare the efficacy and safety of anitocabtagene autoleucel (anito-cel) with standard of care in patients with relapsed and/or refractory multiple myeloma (RRMM) who have received one to three prior lines of therapy, including an immunomodulatory drug (lMiD) and an anti-CD38 monoclonal antibody.

iMMagine-3 will enroll approximately 450 adult patients. Prior to randomization, investigator’s choice of standard of care (SOC) regimens include: pomalidomide, bortezomib, and dexamethasone (PVd); daratumumab, pomalidomide, and dexamethasone (DPd); carfilzomib, daratumumab, and dexamethasone (KDd); or carfilzomib and dexamethasone (Kd). Patients in the anito-cel arm will undergo leukapheresis and optional bridging therapy (with the SOC regimen selected by the investigator prior to randomization) followed by lymphodepleting chemotherapy (fludarabine 30 mg/m2/d and cyclophosphamide 300 mg/m2/d for 3 days) and one infusion of anito-cel (115×106 CAR+ T cells) on Day 1.

The primary endpoint is progression-free survival (PFS) per blinded independent review according to the 2016 IMWG uniform response criteria for multiple myeloma (MM) with the hypothesis that anito-cel will prolong PFS compared to SOC. Key secondary endpoints include complete response rate (CR/sCR), minimal residual disease negativity, overall survival, and safety.

The iMMagine-3 study was initiated in the second half of 2024 at approximately 130 study sites across North America, Europe, and the rest of the world.

About Arcellx and Kite Collaboration

Arcellx and Kite, a Gilead Company, formed a global strategic collaboration and license agreement to co-develop and co-commercialize anito-cel for patients with relapsed and/or refractory multiple myeloma, (RRMM). Anito-cel is currently being developed in a Phase 2 registrational pivotal study and a global Phase 3 randomized controlled study for RRMM. Kite and Arcellx will jointly commercialize the anito-cel asset in the United States, and Kite will commercialize the product outside the United States.

On December 8, 2024 Johnson & Johnson (NYSE:JNJ) reported new frontline data featuring TECVAYLI (teclistamab-cqyv) from two investigational studies in patients with newly diagnosed multiple myeloma (NDMM) in induction and maintenance settings (Press release, Johnson & Johnson, DEC 8, 2024, View Source [SID1234648883]). The MajesTEC-5 (Abstract #493) and MajesTEC-4 (Abstract #494) studies establish the potential of TECVAYLI for use in newly diagnosed patients, with promising efficacy and a tolerable safety profile. These data were highlighted as oral presentations at the 2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.1,2

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Forty-nine patients with transplant-eligible NDMM were treated with TECVAYLI in combination with DARZALEX FASPRO (daratumumab and hyaluronidase-fihj), lenalidomide and dexamethasone (Tec-DRd) or DARZALEX FASPRO, bortezomib, lenalidomide and dexamethasone (Tec-DVRd) as induction therapy in the MajesTEC-5 study.1 All patients who were evaluated for MRD negativity after cycle 3 of induction therapy achieved MRD negativity (10-5) and maintained through cycle 6.1

"These data from the MajesTEC-5 study build on the growing body of evidence of TECVAYLI combinations that support the potential combinability of TECVAYLI with other effective therapies, demonstrating high rates of MRD-negative responses for evaluable patients with newly diagnosed multiple myeloma," said Rachel Kobos, M.D., Vice President, Oncology Research & Development, Johnson & Johnson Innovative Medicine. "At Johnson & Johnson, our deep expertise and understanding of multiple myeloma has shaped the regimens we’re developing, including our bispecific antibodies in new combinations, and we’re committed to exploring the full potential of our therapies to improve outcomes for patients."

The safety profiles were manageable and consistent with individual safety profiles.1 No treatment-emergent adverse events (TEAEs) led to study treatment discontinuation or death; cytokine release syndrome (CRS; Grade 1 or 2) occurred in 65 percent of patients.1 No patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS).1 Grade 3/4 TEAEs included lymphopenia (43 percent), neutropenia (57 percent) and infections (35 percent).1

"There remains opportunity to achieve even deeper and more sustained outcomes for a broader patient population in the frontline setting," said Marc S. Raab, M.D., Heidelberg University Hospital, Germany.* "These data reinforce the potential of TECVAYLI when used in earlier lines and show that TECVAYLI can be leveraged to optimize existing standard regimens in combination."

Results from the safety run-in of the Phase 3 MajesTEC-4 study highlighted the potential of TECVAYLI to be administered as a maintenance therapy following autologous stem cell transplant (ASCT).2 MajesTEC-4 is the first study to present data on a B-cell maturation antigen (BCMA) bispecific as monotherapy or combination therapy after ASCT.2

Low rates of non-hematologic Grade 3/4 TEAEs and discontinuation of treatment due to all TEAEs (5.3 percent) were observed. CRS events were all Grade 1/2, mostly occurring during step-up dosing, and ICANS was not observed. Neutropenia and infections were the most common Grade 3/4 TEAEs.2 Grade 3/4 neutropenia at 6 months showed a decreased trend in cohorts 2 and 3 with less frequent TECVAYLI dosing (cohort 1: 94 percent, cohort 2: 63 percent, cohort 3: 47 percent).2 A similar trend was observed for all-grade infections (cohort 1: 94 percent; cohort 2: 78 percent; cohort 3: 77 percent).2 All evaluable patients in cohort 1 who underwent MRD assessment after 12 months of therapy were MRD negative, and 100 percent of evaluable patients assessed in cohorts 2 and 3 were also MRD negative at cycle 6.2

Further analysis of combination therapies will be evaluated in the Phase 3 MajesTEC-7 study, which is currently enrolling.

About MajesTEC-5 Study
MajesTEC-5 (NCT05695508) is an ongoing, Phase 2 study of teclistamab and talquetamab, evaluating the safety and efficacy of combination regimens in participants with newly diagnosed transplant eligible multiple myeloma.3

About MajesTEC-4 Study
MajesTEC-4 (NCT05243797) is an ongoing, multicenter, randomized, open-label, Phase 3 study of teclistamab in combination with lenalidomide and teclistamab alone versus lenalidomide alone in participants with newly diagnosed multiple myeloma as maintenance therapy following autologous stem cell transplantation.4

About MajesTEC-7 Study
MajesTEC-7 (NCT05552222) is a Phase 3 randomized study comparing teclistamab in combination with daratumumab SC and lenalidomide (Tec-DR) and talquetamab in combination with daratumumab SC and lenalidomide (Tal-DR) versus daratumumab SC, lenalidomide, and dexamethasone (DRd) in participants with newly diagnosed multiple myeloma who are either ineligible or not intended for autologous stem cell transplant as initial therapy.5

About TECVAYLI
TECVAYLI (teclistamab-cqyv) received approval from the U.S. FDA in October 2022 as an off-the-shelf (or ready-to-use) antibody that is administered as a subcutaneous treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.6 The European Commission (EC) granted TECVAYLI conditional marketing authorization (CMA) in August 2022 as monotherapy for the treatment of adult patients with RRMM who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have demonstrated disease progression since the last therapy. In August 2023, the EC granted the approval of a Type II variation application for TECVAYLI, providing the option for a reduced dosing frequency of 1.5 mg/kg every two weeks in patients who have achieved a complete response (CR) or better for a minimum of six months. TECVAYLI is a first-in-class, bispecific T-cell engager antibody therapy that uses innovative science to activate the immune system by binding to the CD3 receptor expressed on the surface of T-cells and to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells. In February 2024, the U.S. FDA approved the supplemental Biologics License Application (sBLA) for TECVAYLI for a reduced dosing frequency of 1.5 mg/kg every two weeks (Q2W) in patients with relapsed or refractory multiple myeloma who have achieved and maintained a CR or better for a minimum of six months.

For more information, visit www.TECVAYLI.com.

About DARZALEX FASPRO and DARZALEX
DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for nine indications in multiple myeloma, four of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible. It is the only subcutaneous CD38-directed antibody approved to treat patients with MM. DARZALEX FASPRO is co-formulated with recombinant human hyaluronidase PH20, Halozyme’s ENHANZE drug delivery technology.

DARZALEX is the first CD38-directed antibody approved to treat multiple myeloma. DARZALEX-based regimens have been used in the treatment of more than 585,000 patients worldwide and more than 239,000 patients in the U.S. alone.

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.

For more information, visit View Source

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.7 In multiple myeloma, these plasma cells proliferate and spread rapidly and replace normal cells in the bone marrow with tumors.8 Multiple myeloma is the third most common blood cancer worldwide and remains an incurable disease.9 In 2024, it was estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people would die from the disease.10 People living with multiple myeloma have a 5-year survival rate of 59.8 percent.11 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels and kidney problems or infections.12,13

TECVAYLI IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-
ASSOCIATED NEUROTOXICITY SYNDROME

Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving
TECVAYLI. Initiate treatment with TECVAYLI step-up dosing schedule to reduce risk of CRS. Withhold TECVAYLI
until CRS resolves or permanently discontinue based on severity.

Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious and life-
threatening reactions, can occur in patients receiving TECVAYLI. Monitor patients for signs or symptoms of neurologic
toxicity, including ICANS, during treatment. Withhold TECVAYLI until neurologic toxicity resolves or permanently
discontinue based on severity.

TECVAYLI is available only through a restricted program called the TECVAYLI and TALVEY Risk Evaluation and
Mitigation Strategy (REMS).

INDICATION AND USAGE

TECVAYLI (teclistamab-cqyv) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.

This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

WARNINGS AND PRECAUTIONS

Cytokine Release Syndrome – TECVAYLI can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 72% of patients who received TECVAYLI at the recommended dose, with Grade 1 CRS occurring in 50% of patients, Grade 2 in 21%, and Grade 3 in 0.6%. Recurrent CRS occurred in 33% of patients. Most patients experienced CRS following step-up dose 1 (42%), step-up dose 2 (35%), or the initial treatment dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI. The median time to onset of CRS was 2 (range: 1 to 6) days after the most recent dose with a median duration of 2 (range: 1 to 9) days. Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation).

Initiate therapy according to TECVAYLI step-up dosing schedule to reduce risk of CRS. Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI accordingly. At the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold or permanently discontinue TECVAYLI based on severity.

TECVAYLI is available only through a restricted program under a REMS.

Neurologic Toxicity including ICANS – TECVAYLI can cause serious or life-threatening neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

In the clinical trial, neurologic toxicity occurred in 57% of patients who received TECVAYLI at the recommended dose, with Grade 3 or 4 neurologic toxicity occurring in 2.4% of patients. The most frequent neurologic toxicities were headache (25%), motor dysfunction (16%), sensory neuropathy (15%), and encephalopathy (13%). With longer follow-up, Grade 4 seizure and fatal Guillain-Barré syndrome (one patient each) occurred in patients who received TECVAYLI.

In the clinical trial, ICANS was reported in 6% of patients who received TECVAYLI at the recommended dose. Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent doses of TECVAYLI. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.

Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or permanently discontinue TECVAYLI based on severity per recommendations and consider further management per current practice guidelines.

Due to the potential for neurologic toxicity, patients are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves.

TECVAYLI is available only through a restricted program under a REMS.

TECVAYLI and TALVEY REMS – TECVAYLI is available only through a restricted program under a REMS called the TECVAYLI and TALVEY REMS because of the risks of CRS and neurologic toxicity, including ICANS.

Hepatotoxicity – TECVAYLI can cause hepatotoxicity, including fatalities. In patients who received TECVAYLI at the recommended dose in the clinical trial, there was one fatal case of hepatic failure. Elevated aspartate aminotransferase (AST) occurred in 34% of patients, with Grade 3 or 4 elevations in 1.2%. Elevated alanine aminotransferase (ALT) occurred in 28% of patients, with Grade 3 or 4 elevations in 1.8%. Elevated total bilirubin occurred in 6% of patients with Grade 3 or 4 elevations in 0.6%. Liver enzyme elevation can occur with or without concurrent CRS.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.

Infections – TECVAYLI can cause severe, life-threatening, or fatal infections. In patients who received TECVAYLI at the recommended dose in the clinical trial, serious infections, including opportunistic infections, occurred in 30% of patients, with Grade 3 or 4 infections in 35%, and fatal infections in 4.2%. Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI and treat appropriately. Administer prophylactic antimicrobials according to guidelines. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.

Monitor immunoglobulin levels during treatment with TECVAYLI and treat according to guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

Neutropenia – TECVAYLI can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI at the recommended dose in the clinical trial, decreased neutrophils occurred in 84% of patients, with Grade 3 or 4 decreased neutrophils in 56%. Febrile neutropenia occurred in 3% of patients.

Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines. Monitor patients with neutropenia for signs of infection. Withhold TECVAYLI based on severity.

Hypersensitivity and Other Administration Reactions – TECVAYLI can cause both systemic administration-related and local injection-site reactions. Systemic Reactions – In patients who received TECVAYLI at the recommended dose in the clinical trial, 1.2% of patients experienced systemic-administration reactions, which included Grade 1 recurrent pyrexia and Grade 1 swollen tongue. Local Reactions – In patients who received TECVAYLI at the recommended dose in the clinical trial, injection-site reactions occurred in 35% of patients, with Grade 1 injection-site reactions in 30% and Grade 2 in 4.8%. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.

Embryo-Fetal Toxicity – Based on its mechanism of action, TECVAYLI may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI and for 5 months after the last dose.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.

Please read full Prescribing Information, including Boxed WARNING, for TECVAYLI.

DARZALEX FASPRO INDICATIONS AND IMPORTANT SAFETY INFORMATION 

INDICATIONS
DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:

In combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor (PI)
In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
As monotherapy in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent
IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS 
DARZALEX FASPRO is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.

WARNINGS AND PRECAUTIONS  

Hypersensitivity and Other Administration Reactions  
Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO.

Systemic Reactions  
In a pooled safety population of 1249 patients with multiple myeloma (N=1056) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO as monotherapy or in combination, 7% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 0.7%, Grade 4: 0.1%). Systemic administration-related reactions occurred in 7% of patients with the first injection, 0.2% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 2.9 hours (range: 5 minutes to 3.5 days). Of the 165 systemic administration-related reactions that occurred in 93 patients, 144 (87%) occurred on the day of DARZALEX FASPRO administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.

Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.  

Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.  

Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO.  

Local Reactions  
In this pooled safety population, injection-site reactions occurred in 7% of patients, including Grade 2 reactions in 0.8%. The most frequent (>1%) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO. Monitor for local reactions and consider symptomatic management.  

Neutropenia  
Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO, higher rates of Grade 3-4 neutropenia were observed.  

Thrombocytopenia  
Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX FASPRO until recovery of platelets.  

Embryo-Fetal Toxicity  
Based on the mechanism of action, DARZALEX FASPRO can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO and for 3 months after the last dose.  

The combination of DARZALEX FASPRO with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.  

Interference With Serological Testing  
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted.  

Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO. Type and screen patients prior to starting DARZALEX FASPRO.  

Interference With Determination of Complete Response  
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO-treated patients with IgG kappa myeloma protein.  

ADVERSE REACTIONS  

In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral sensory neuropathy, constipation, pneumonia, and peripheral edema.  

The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.  

Please click here to see the full Prescribing Information for DARZALEX FASPRO.