On December 5, 2020 AbbVie (NYSE: ABBV) reported new data from the Phase 2 CAPTIVATE (PCYC-1142) clinical trial evaluating IMBRUVICA (ibrutinib) in combination with VENCLEXTA/VENCLYXTO (venetoclax) in previously untreated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) during an oral presentation session at the virtual 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Abstract #123) (Press release, AbbVie, DEC 5, 2020, View Source [SID1234572267]). The one-year disease-free survival (DFS) rate in patients randomized to placebo or ibrutinib after completing the combination regimen provides data to support a fixed-duration treatment that can offer CLL/SLL patients remission and time off treatment.

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"These results show the ibrutinib plus venetoclax combination providing continued disease-free survival for CLL patients once treatment is complete," said Dr. William Wierda, M.D., Professor, Department of Leukemia, University of Texas MD Anderson Cancer Center and principal study investigator. "It will be really exciting for patients to have a potential option in the future that can put them into remission and time off treatment."

These findings build on the previously reported results showing that this first-line combination regimen for CLL resulted in high rates of undetectable minimal residual disease (uMRD) in both peripheral blood (PB) (75% of patients) and in bone marrow (BM) (72% of patients). Undetectable MRD is defined as little to no cancer cells found after treatment. In the Confirmed uMRD group, one-year DFS rate was not significantly different for patients randomized to placebo (95.3%; 95% CI 82.7-98.8) versus ibrutinib (100%; 95% CI 100-100) (P=0.1475).

During the overall study period across all-treated patients (with median treatment duration of 29 months), most common grade 3/4 adverse events (≥5% of patients) were neutropenia (36%), hypertension (10%), thrombocytopenia (5%), and diarrhea (5%). The safety profile of the combination was consistent with known adverse events for ibrutinib and venetoclax individually and no new safety signals emerged.

"IMBRUVICA and VENCLEXTA/VENCLYXTO, individually, have truly transformed the way CLL and some other blood cancers are treated. Today, CLL can be treated without chemotherapy in the form of an oral pill, which is a remarkable advancement, compared to standards of care over the last decade," said Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology development, AbbVie. "The results from this study will add to the evidence required for the development of this combination regimen as a potential new treatment option for CLL."

CLL is one of the two most common forms of leukemia in adults and is a type of cancer that can develop from cells in the bone marrow that later mature into certain white blood cells (called lymphocytes).1 While these cancer cells start in the bone marrow, they then later spread into the blood. The prevalence of CLL is approximately 115,000 patients in the U.S. with approximately 20,000 newly diagnosed patients every year.2,3 CLL is predominately a disease of the elderly, with a median age at diagnosis ranging from 65-70 years.4

According to the Leukemia & Lymphoma Society, MRD refers to the small number of cancer cells that remain in the body after treatment.5 The number of remaining cells may be so small that they do not cause any physical signs or symptoms and often cannot even be detected through traditional methods, this is known as undetectable MRD (uMRD). Doctors use MRD/uMRD to measure the effectiveness of treatment and to predict which patients are at risk of relapse.

There are additional ongoing company-sponsored trials exploring the potential of ibrutinib and venetoclax in combination for CLL treatment, including the Phase 3 GLOW study. Results from the ongoing GLOW study, assessing the ibrutinib plus venetoclax combination in comparison to chlorambucil plus obinutuzumab for first-line treatment of patients with CLL or SLL (NCT03462719), will be presented at an upcoming congress.

About CAPTIVATE
The CAPTIVATE study MRD cohort evaluated 164 patients between the ages of 18 and 70 years old with previously untreated CLL/SLL. Patients received 3 cycles of ibrutinib lead-in followed by 12 cycles of ibrutinib + venetoclax (Ibr 420 mg/day PO; Ven ramp-up to 400 mg/day PO). Patients with confirmed uMRD (defined as uMRD serially over ≥3 cycles, and in both PB and BM) after 12 cycles of ibrutinib + venetoclax were randomized 1:1 to receive double-blind treatment with placebo or ibrutinib. Patients who did not meet the definition of confirmed uMRD were randomized 1:1 to receive open-label treatment with ibrutinib or continued ibrutinib + venetoclax. Primary endpoint was 1-year DFS rate in the confirmed uMRD patients randomized to placebo vs ibrutinib; DFS was defined as survival without progression or MRD relapse (which was defined as an MRD level of 10-2). Key secondary endpoints were rates of uMRD (<10-4 by 8-color flow cytometry), response per iwCLL, adverse events (AEs), as well as progression-free survival (PFS). The safety profile of the combination was consistent with known adverse events for ibrutinib and venetoclax individually and no new safety signals emerged.

The depth of response achieved with this regimen is reflected in the 30-month progression-free survival (PFS) rate of ~95% across all treated patients, including the subset receiving placebo after the fixed duration treatment.

About Ibrutinib (IMBRUVICA)
IMBRUVICA (ibrutinib) is a once-daily, first-in-class BTK inhibitor that is administered orally, and is jointly developed and commercialized by Pharmacyclics, LLC, an AbbVie Company, and Janssen Biotech, Inc. (Janssen). The BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signaling is needed by specific cancer cells to multiply and spread.6,7 By blocking BTK, IMBRUVICA may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.8

Since its launch in 2013, IMBRUVICA has received 11 FDA approvals across six disease areas: chronic lymphocytic leukemia (CLL) with or without 17p deletion (del17p); small lymphocytic lymphoma (SLL) with or without del17p; Waldenström macroglobulinemia; previously-treated patients with mantle cell lymphoma (MCL)*; previously-treated patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy* – and previously-treated patients with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.9

IMBRUVICA is now approved in 101 countries and has been used to treat more than 200,000 patients worldwide across its approved indications. IMBRUVICA is the only FDA-approved medicine in WM and cGVHD. IMBRUVICA has been granted four Breakthrough Therapy Designations from the U.S. FDA. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases. IMBRUVICA was one of the first medicines to receive FDA approval via the Breakthrough Therapy Designation pathway.

As of early 2019, the National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of 28 leading cancer centers devoted to patient care, research, and education, recommends ibrutinib (IMBRUVICA) as a preferred regimen for the initial treatment of CLL/SLL and has Category 1 treatment status for treatment-naïve patients without deletion 17p. In February 2020, the NCCN Guidelines were updated to elevate IMBRUVICA with or without rituximab from other recommended regimens to a preferred regimen for the treatment of relapsed/refractory MCL. In September 2020, the NCCN guidelines were updated to elevate IMBRUVICA with or without rituximab as the only Category 1 preferred regimen for treatment-naïve WM patients.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA is the most comprehensively studied BTK inhibitor, with more than 150 ongoing clinical trials. There are approximately 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and more than 100 investigator-sponsored trials and external collaborations that are active around the world. For more information, visit www.IMBRUVICA.com.

*Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Side Effect Information
Before taking IMBRUVICA, tell your healthcare provider about all of your medical conditions, including if you:

have had recent surgery or plan to have surgery. Your healthcare provider may stop IMBRUVICA for any planned medical, surgical, or dental procedure.
have bleeding problems.
have or had heart rhythm problems, smoke, or have a medical condition that increases your risk of heart disease, such as high blood pressure, high cholesterol, or diabetes.
have an infection.
have liver problems.
are pregnant or plan to become pregnant. IMBRUVICA can harm your unborn baby. If you are able to become pregnant, your healthcare provider will do a pregnancy test before starting treatment with IMBRUVICA. Tell your healthcare provider if you are pregnant or think you may be pregnant during treatment with IMBRUVICA.
Females who are able to become pregnant should use effective birth control (contraception) during treatment with IMBRUVICA and for 1 month after the last dose.
Males with female partners who are able to become pregnant should use effective birth control, such as condoms, during treatment with IMBRUVICA and for 1 month after the last dose.
are breastfeeding or plan to breastfeed. Do not breastfeed during treatment with IMBRUVICA and for 1 week after the last dose.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking IMBRUVICA with certain other medicines may affect how IMBRUVICA works and can cause side effects.

How should I take IMBRUVICA?

Take IMBRUVICA exactly as your healthcare provider tells you to take it.
Take IMBRUVICA 1 time a day.
Swallow IMBRUVICA capsules or tablets whole with a glass of water.
Do not open, break or chew IMBRUVICA capsules.
Do not cut, crush or chew IMBRUVICA tablets.
Take IMBRUVICA at about the same time each day.
If you miss a dose of IMBRUVICA take it as soon as you remember on the same day. Take your next dose of IMBRUVICA at your regular time on the next day. Do not take extra doses of IMBRUVICA to make up for a missed dose.
If you take too much IMBRUVICA call your healthcare provider or go to the nearest hospital emergency room right away.
What should I avoid while taking IMBRUVICA?

You should not drink grapefruit juice, eat grapefruit, or eat Seville oranges (often used in marmalades) during treatment with IMBRUVICA. These products may increase the amount of IMBRUVICA in your blood.
What are the possible side effects of IMBRUVICA?

IMBRUVICA may cause serious side effects, including:

Bleeding problems (hemorrhage) are common during treatment with IMBRUVICA, and can also be serious and may lead to death. Your risk of bleeding may increase if you are also taking a blood thinner medicine. Tell your healthcare provider if you have any signs of bleeding, including: blood in your stools or black stools (looks like tar), pink or brown urine, unexpected bleeding, or bleeding that is severe or that you cannot control, vomit blood or vomit looks like coffee grounds, cough up blood or blood clots, increased bruising, dizziness, weakness, confusion, change in your speech, or a headache that lasts a long time or severe headache.
Infections can happen during treatment with IMBRUVICA. These infections can be serious and may lead to death. Tell your healthcare provider right away if you have fever, chills, weakness, confusion, or other signs or symptoms of an infection during treatment with IMBRUVICA.
Decrease in blood cell counts. Decreased blood counts (white blood cells, platelets, and red blood cells) are common with IMBRUVICA, but can also be severe. Your healthcare provider should do monthly blood tests to check your blood counts.
Heart rhythm problems (ventricular arrhythmias, atrial fibrillation and atrial flutter). Serious heart rhythm problems and death have happened in people treated with IMBRUVICA, especially in people who have an increased risk for heart disease, have an infection, or who have had heart rhythm problems in the past. Tell your healthcare provider if you get any symptoms of heart rhythm problems, such as feeling as if your heart is beating fast and irregular, lightheadedness, dizziness, shortness of breath, chest discomfort, or you faint. If you develop any of these symptoms, your healthcare provider may do a test to check your heart (ECG) and may change your IMBRUVICA dose.
High blood pressure (hypertension). New or worsening high blood pressure has happened in people treated with IMBRUVICA. Your healthcare provider may start you on blood pressure medicine or change current medicines to treat your blood pressure.
Second primary cancers. New cancers have happened during treatment with IMBRUVICA, including cancers of the skin or other organs.
Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure and the need for dialysis treatment, abnormal heart rhythm, seizure, and sometimes death. Your healthcare provider may do blood tests to check you for TLS.
The most common side effects of IMBRUVICA in adults with B-cell malignancies (MCL, CLL/SLL, WM and MZL) include:

diarrhea
tiredness
muscle and bone pain
rash
bruising
The most common side effects of IMBRUVICA in adults with cGVHD include:

tiredness
bruising
diarrhea
mouth sores (stomatitis)
muscle spasms
nausea
pneumonia
Diarrhea is a common side effect in people who take IMBRUVICA. Drink plenty of fluids during treatment with IMBRUVICA to help reduce your risk of losing too much fluid (dehydration) due to diarrhea. Tell your healthcare provider if you have diarrhea that does not go away.

These are not all the possible side effects of IMBRUVICA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of IMBRUVICA

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use IMBRUVICA for a condition for which it was not prescribed. Do not give IMBRUVICA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about IMBRUVICA that is written for health professionals.

Please click here for full Prescribing Information.

About VENCLEXTA (venetoclax)
VENCLEXTA (venetoclax) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. VENCLEXTA targets the BCL-2 protein and works to help restore the process of apoptosis.

VENCLEXTA/VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research and to studying venetoclax in clinical trials across several blood and other cancers. VENCLEXTA/VENCLYXTO is approved in more than 50 countries, including the U.S.

Uses and Important VENCLEXTA (venetoclax) U.S. Safety Information10

Uses
VENCLEXTA is a prescription medicine used:

to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML) who:
are 75 years of age or older, or
have other medical conditions that prevent the use of standard chemotherapy.
It is not known if VENCLEXTA is safe and effective in children.

Important Safety Information
What is the most important information I should know about VENCLEXTA?
VENCLEXTA can cause serious side effects, including:
Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. Your healthcare provider will do tests to check your risk of getting TLS before you start taking VENCLEXTA. You will receive other medicines before starting and during treatment with VENCLEXTA to help reduce your risk of TLS. You may also need to receive intravenous (IV) fluids into your vein. Your healthcare provider will do blood tests to check for TLS when you first start treatment and during treatment with VENCLEXTA.It is important to keep your appointments for blood tests. Tell your healthcare provider right away if you have any symptoms of TLS during treatment with VENCLEXTA, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain.

Drink plenty of water during treatment with VENCLEXTA to help reduce your risk of getting TLS. Drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before your first dose, on the day of your first dose of VENCLEXTA, and each time your dose is increased.

Your healthcare provider may delay, decrease your dose, or stop treatment with VENCLEXTA if you have side effects.

Who should not take VENCLEXTA?
Certain medicines must not be taken when you first start taking VENCLEXTA and while your dose is being slowly increased because of the risk of increased TLS.

Tell your healthcare provider about all the medicines you take, including prescription and over-the counter medicines, vitamins, and herbal supplements. VENCLEXTA and other medicines may affect each other causing serious side effects.
Do not start new medicines during treatment with VENCLEXTA without first talking with your healthcare provider.
Before taking VENCLEXTA, tell your healthcare provider about all of your medical conditions, including if you:

have kidney or liver problems.
have problems with your body salts or electrolytes, such as potassium, phosphorus, or calcium.
have a history of high uric acid levels in your blood or gout.
are scheduled to receive a vaccine. You should not receive a "live vaccine" before, during, or after
treatment with VENCLEXTA, until your healthcare provider tells you it is okay. If you are not sure about the type of immunization or vaccine, ask your healthcare provider. These vaccines may not be safe or may not work as well during treatment with VENCLEXTA.
are pregnant or plan to become pregnant. VENCLEXTA may harm your unborn baby. If you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with VENCLEXTA, and you should use effective birth control during treatment and for at least 30 days after the last dose of VENCLEXTA. If you become pregnant or think you are pregnant, tell your healthcare provider right away.
are breastfeeding or plan to breastfeed. It is not known if VENCLEXTA passes into your breast milk. Do not breastfeed during treatment with VENCLEXTA and for 1 week after the last dose.
What should I avoid while taking VENCLEXTA?
You should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit while you are taking VENCLEXTA. These products may increase the amount of VENCLEXTA in your blood.

What are the possible side effects of VENCLEXTA?
VENCLEXTA can cause serious side effects, including:

Low white blood cell counts (neutropenia). Low white blood cell counts are common with VENCLEXTA, but can also be severe. Your healthcare provider will do blood tests to check your blood counts during treatment with VENCLEXTA and may pause dosing.
Infections. Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with VENCLEXTA. Your healthcare provider will closely monitor and treat you right away if you have a fever or any signs of infection during treatment with VENCLEXTA.
Tell your healthcare provider right away if you have a fever or any signs of an infection during treatment with VENCLEXTA.

The most common side effects of VENCLEXTA when used in combination with obinutuzumab or rituximab or alone in people with CLL or SLL include low white blood cell counts; low platelet counts; low red blood cell counts; diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swelling of your arms, legs, hands, and feet.

The most common side effects of VENCLEXTA in combination with azacitidine or decitabine or low-dose cytarabine in people with AML include nausea; diarrhea; low platelet count; constipation; low white blood cell count; fever with low white blood cell count; tiredness; vomiting; swelling of arms, legs, hands, or feet; fever; infection in lungs; shortness of breath; bleeding; low red blood cell count; rash; stomach (abdominal) pain; infection in your blood; muscle and joint pain; dizziness; cough; sore throat; and low blood pressure.

VENCLEXTA may cause fertility problems in males. This may affect your ability to father a child. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of VENCLEXTA. Call your doctor for medical advice about side effects.

You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

If you cannot afford your medication, contact genentech-access.com/patient/brands/venclexta for assistance.

The full U.S. prescribing information, including Medication Guide, for VENCLEXTA can be found here.
Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie in Oncology
At AbbVie, we strive to discover and develop medicines that deliver transformational improvements in cancer treatment by uniquely combining our deep knowledge in core areas of biology with cutting-edge technologies, and by working together with our partners – scientists, clinical experts, industry peers, advocates, and patients. We remain focused on delivering these transformative advances in treatment across some of the most debilitating and widespread cancers. We are also committed to exploring solutions to help patients obtain access to our cancer medicines. AbbVie’s oncology portfolio now consists of marketed medicines and a pipeline containing multiple new molecules being evaluated worldwide in more than 300 clinical trials and more than 20 different tumor types. For more information, please visit View Source

On December 5, 2020 Poseida Therapeutics, Inc. (NASDAQ:PSTX), a clinical-stage biopharmaceutical company utilizing proprietary gene engineering platform technologies to create cell and gene therapeutics with the capacity to cure, today reported results of an ongoing Phase 1 clinical trial of P-BCMA-101, an autologous chimeric antigen receptor T-cell (CAR-T) product candidate in relapsed/refractory multiple myeloma, during an oral presentation at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Poseida Therapeutics, DEC 5, 2020, View Source [SID1234572266]). The results show that patients treated with equivalent doses of product manufactured with a modified nanoplasmid process in the expanded Phase 1 trial achieved deeper responses while maintaining a similar safety profile compared to product manufactured with the Company’s legacy plasmid.

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"Based on the dual benefits of improved efficacy and consistent safety demonstrated with the new nanoplasmid, we are moving forward with this optimized manufacturing method in all of our CAR-T programs," said Eric Ostertag, M.D., Ph.D., chief executive officer of Poseida Therapeutics. "Furthermore, using our first-generation plasmid, we saw higher response rates as we escalated to higher dose cohorts not yet reached with the nanoplasmid product. We are currently moving into higher dosing cohorts with the nanoplasmid manufactured P-BCMA-101 product candidate and are optimistic further increases in effectiveness and durability are possible at these higher doses. We expect to finalize our Phase 2 dose in the first quarter of 2021."

The Phase 1 dose escalation trial initially included five cohorts with a product candidate created using a standard plasmid process. The trial was expanded in 2020 to include cohorts utilizing a new nanoplasmid manufacturing process. The nanoplasmid technology allows for a reduction in the plasmid backbone size, enhancing the transposition efficiency during manufacturing and improving the final CAR-T product performance. The expansion part of the trial is also evaluating several novel dosing strategies with 19 patients treated as of the data cutoff with a variety of dosing regimens, including single administration, cyclic dosing, combination with rituximab, and combination with lenalidomide.

Using the new manufacturing process, a dose of 0.75 x 106 cells/kg was administered to eight patients in the initial P-BCMA-101 nanoplasmid expansion cohorts. Patients treated in this cohort and evaluable by International Myeloma Working Group (IMWG) criteria (n=6) showed a higher response rate, with an ORR of 67 percent as compared to an ORR of 50 percent for the same dosing cohort using the standard P-BCMA-101 plasmid (n=2). Additionally, as of the cutoff date, three patients achieved deeper responses of either very good partial response (VGPR) or complete response (CR) in the nanoplasmid expansion cohort as compared to no patients reaching a VGPR or CR in the standard plasmid group at the Cohort 1 dose. As of the data cutoff date, two of the three nanoplasmid patients who reached VGPR or CR remained in durable responses at approximately 6 months.

"We observed an excellent efficacy and safety profile with a single dose escalation. There were very low rates of CRS with no ICU admissions for CRS, resulting in a safety profile suggesting this therapy could be delivered to a greater number of patients in a community hospital or outpatient setting," said Caitlin Costello, MD, Associate Clinical Professor of Medicine and member of the Division of Blood and Marrow Transplantation at University of California, San Diego. Dr. Costello is the principal investigator in the study, who presented the data during the ASH (Free ASH Whitepaper) meeting.

At the 0.75 x 106 cells/kg dose, cytokine release syndrome (CRS) was seen in just one, or 12.5%, of evaluable Phase 1 nanoplasmid patients (n=8) and neurotoxicity was not seen in any patients, demonstrating the preservation of the product safety profile within the expansion cohort. The Company believes this highly favorable safety profile can be attributed to the gradual expansion of stem cell memory T (Tscm) cells when compared with published data from competitor products comprised of a higher percentage of T effector and other differentiated T cells (2-3 weeks to peak versus 3-7 days for most CAR-T cells). There have been no patient deaths, dose limiting toxicities or unexpected/off-target toxicities related to P-BCMA-101. The most common adverse events were cytopenias and infections generally attributable to lymphodepleting chemotherapy regimens. Based on the safety results, the protocol was amended to allow fully outpatient CAR-T cell administration.

The median patient age was 60, with a median time since diagnosis of approximately five years. Patients were heavily pre-treated, with a median of eight prior lines of therapy (2-18). All patients had received a protease inhibitor or at least one IMid, and nearly all patients had been previously treated with a CD38 monoclonal antibody. Sixty percent of the patients were refractory to all three drug classes, and four patients had previously received an anti-BCMA targeted therapy.

This open label, multicenter Phase 1 study is designed to assess the safety of P-BCMA-101 in subjects with relapsed and/or refractory multiple myeloma and includes multiple exploratory cohorts to evaluate the administration of P-BCMA-101 CAR-T within the framework of moving from the standard plasmid CAR-T product to the nanoplasmid product. The primary objective of this study is to determine the safety and maximum-tolerated dose of P-BCMA-101. Secondary objectives include anti-myeloma effect of P-BCMA-101. Additional information about the Phase 1 clinical study of P-BCMA-101 is available at www.clinicaltrials.gov using identifier: NCT03288493.

About P-BCMA-101
P-BCMA-101 is an autologous CAR-T therapy which is currently being evaluated in an expanded Phase 1 clinical trial for the treatment of patients with relapsed/refractory multiple myeloma to inform the potentially registrational Phase 2 clinical trial. P-BCMA-101 targets cells that express B cell maturation antigen, or BCMA, which is expressed on essentially all multiple myeloma cells. P-BCMA-101 is engineered with Poseida’s non-viral piggyBac DNA Modification System, resulting in a high percentage of T stem cell memory cells. P-BCMA-101 is composed primarily of Tscm, a very young subset of T cells that are long-lived, self-renewing and multipotent, with the capacity to reconstitute the entire spectrum of T cell subsets, including T effector cells. They also survive for decades, and potentially for entire lifespans, with non-CAR-Tscm cells normally providing lifelong T cell immunity against some infectious agents. P-BCMA-101 received regenerative medicine advanced therapy (RMAT) status and orphan drug designation from the FDA. Preliminary results from the Company’s ongoing Phase 1 clinical trial suggest that P-BCMA-101 may have improved response rates with a favorable safety profile compared to published results from clinical trials of other CAR-T therapies at similar doses. The Phase 1 study is funded in part by the California Institute for Regenerative Medicine.

On December 5, 2020 Amgen (NASDAQ:AMGN) reported the first presentation of clinical safety and efficacy data from the Phase 1 study of AMG 701 in heavily pre-treated patients with relapsed/refractory multiple myeloma (R/R MM) (Press release, Amgen, DEC 5, 2020, View Source [SID1234572265]). AMG 701 is an investigational half-life extended (HLE) bispecific T cell engager (BiTE) immuno-oncology therapy targeting B-cell maturation antigen (BCMA). The data will be presented during a live oral presentation on Dec. 5 at the virtual 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition.

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"The emerging data from the BiTE platform in hematological malignancies are encouraging. Previously, Amgen provided important evidence for BCMA-directed BiTE molecules as a therapeutic approach in multiple myeloma. AMG 701 continues to show the potential of that strategy in patients who are heavily pre-treated," said David M. Reese, M.D., executive vice president of Research and Development at Amgen.

"These data are the latest in a series that reinforce both the potential versatility of the BiTE platform and Amgen’s commitment to developing innovative medicines for novel targets in difficult-to-treat cancers," Reese continued. "This year alone, Amgen has presented proof-of-concept data for four BiTE molecules in hematological malignancies and solid tumors, and we are proud to end the year with these data in multiple myeloma at ASH (Free ASH Whitepaper)."

This interim analysis of the Phase 1 dose escalation study evaluated AMG 701 in 85 R/R MM patients who had received at least three prior lines of therapy, and a median of six lines. The response rate was 36% at doses of 3-18 mg with responses lasting up to 26 months in one patient. Six of seven patients, who were tested for minimal residual disease (MRD), were MRD-negative. In the most recent evaluable cohort, there was an 83% ORR, with 4/5 responders being triple refractory.

"Despite advances in the treatment of multiple myeloma, there remains an unmet need for patients with this difficult-to-treat disease who have relapsed or refractory disease following current standard therapies," said Professor Simon J. Harrison, director of the Centre of Excellence in Cellular Immunotherapy, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia. "These first-in-human data show that AMG 701, a half-life extended BiTE therapy targeting BCMA, has encouraging signs of activity as a single agent in this heavily pre-treated patient population."

The most common hematological adverse events (AEs) were anemia (42%), neutropenia (25%) and thrombocytopenia (21%). The most common non-hematological AEs were cytokine release syndrome (CRS, 65%), diarrhea (31%) and hypophosphatemia (31%). CRS was mostly grade 1 (27%) or 2 (28%) based on Lee Blood 2014 criteria. All Grade 3 CRS events (9%) were reversible with mitigation procedures outlined in the study protocol, with a median duration of two days.

Learn more about Amgen’s development of innovative medicines for novel targets in difficult-to-treat tumors at AmgenOncology.com/medical, and follow Amgen Oncology on Twitter and LinkedIn.

About BiTE Technology

BiTE (bispecific T cell engager) technology is a targeted immuno-oncology platform that is designed to engage patient’s own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing more than a dozen BiTE molecules across a broad range of hematologic malignancies and solid tumors, further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE technology, visit www.AmgenBiTETechnology.com.

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse.1 It is a rare and life-threatening disease that accounts for approximately one percent of all cancers.2,3 Worldwide, approximately 160,000 people are diagnosed with multiple myeloma each year, and 106,000 patient deaths are reported on an annual basis.2

About Amgen Oncology

Amgen Oncology is searching for and finding answers to incredibly complex questions that will advance care and improve lives for cancer patients and their families. Our research drives us to understand the disease in the context of the patient’s life – not just their cancer journey – so they can take control of their lives.

For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company’s history, moving with great speed to advance those innovations for the patients who need them.

At Amgen, we are driven by our commitment to transform the lives of cancer patients and keep them at the center of everything we do.

On December 5, 2020 Gracell Biotechnologies Inc. ("Gracell"), a global clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer, reported an interim readout to evaluate the safety and efficacy of its potential first-in-class GC012F FasTCAR-enabled dual-targeting BCMA/CD19 cell therapy in patients with relapsed or refractory multiple myeloma (R/R MM) (Press release, Gracell Biotechnologies, DEC 5, 2020, View Source [SID1234572264]). The data were presented by Dr. Weijun Fu, Professor of Hematology, Director at Shanghai Changzheng Hospital, as an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper)’s (ASH) (Free ASH Whitepaper) 2020 Annual Meeting.

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GC012F, a dual BCMA/CD19 targeting CAR-T cell therapy developed on Gracell’s FasTCAR platform – which enables next-day manufacturing – was evaluated in an investigator-initiated Phase 1 trial. As of July 17th, the study enrolled sixteen patients at three dose levels with the highest dose level of 3×10^5 cells per kg. After three days of a standard lymphodepleting regimen, patients received GC012F as a single infusion over 30 minutes.

Early Overall Response Rate (ORR) showed a promising 93.7% with all responses being VGPR or better – showing fast, deep and durable responses in all dose levels
100% of the patients treated at the highest dose level (n=6) obtained a MRD negative sCR which was maintained through the landmark analysis of six months (n=4) at the time of data cut off
The median duration of follow up at time of assessment was 7.3 months (range 1–10 months). Of the sixteen patients treated, 93.7% were classified as high-risk according to mSMART 3.0 guidelines, 19% had double hit R/R MM, and 31% had extramedullary disease. Patients had received a median of 5 prior lines of therapy, with 75% being refractory to last therapy and 19% being primary refractory. 94% of the patients were triple exposed to a PI, IMiD, and at least a third treatment modality, including anti-CD38 targeted therapy. 63% were penta-exposed with at least five different treatment modalities, including PI, IMiD and others. One patient with extramedullary disease obtained MRD negative result at his first bone marrow assessment at month 1, however, he was considered a non-responder based on the increasing size of the extramedullary lesion at month 1.

The safety profile of GC012F was manageable with an overall low grade of cytokine release syndrome (CRS) (87.5 % Grade 1/2, 2 patients Grade 3, no Grade 4 or 5) and a median duration of four days ranging from 1–8 days. CRS was treated with Standard of Care treatment, including tocilizumab and steroids, and resolved in all cases. No ICANS (immune effector cell-associated neurotoxicity) was observed in any of the sixteen patients. Treatment-emergent adverse events (TEAEs) presented predominantly as cytopenias and AST increase. Lower respiratory tract infection was observed in three patients. All TEAEs were resolved with standard therapy.

"We are extremely encouraged about these early findings in sixteen patients with predominately high-risk features," said Dr. Martina Sersch, MD, PhD, CMO of Gracell. "High-risk patients are difficult to treat successfully and to achieve longer-term remission. A 100% MRD-sCR at month six post-infusion after treatment with GC012F at the highest dose level shows promise for heavily pretreated patients who have failed or were no longer responding to standard treatment options. We are planning to expand our program globally and are looking forward to sharing updates as we advance our programs through clinical development."

On December 5, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reported initial data for the Phase 1 first-in-human dose escalation study of talquetamab (JNJ-64407564) for the treatment of relapsed or refractory multiple myeloma (NCT03399799) (Press release, Janssen Pharmaceuticals, DEC 5, 2020, View Source [SID1234572263]). Talquetamab is a first-in-class, and the only investigational bispecific antibody that targets both GPRC5D, a novel multiple myeloma target, and CD3 on T-cells. Initial results for both the subcutaneous (SC) and intravenous (IV) formulations show encouraging clinical activity against the GPRC5D target, which is highly expressed on multiple myeloma cells and associated with poor prognostic factors.1,2,3 At the SC recommended Phase 2 dose (RP2D), the overall response rate (ORR) was 69 percent (9/13) and 39 percent achieved a very good partial response (VGPR) or better. The data will be featured during the American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Annual Meeting as an oral presentation on Saturday, December 5 at 5:00 p.m. ET (Abstract #290).

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"There is a pressing need for continued innovation of multiple myeloma treatments – particularly for patients who have relapsed on other therapies – and the results presented today for talquetamab are encouraging," said Ajai Chari, M.D., Professor of Medicine, the Director of Clinical Research in the Multiple Myeloma Program, and the Associate Director of Clinical Research, Mount Sinai Cancer Clinical Trials Office. "The Phase 1 overall response rate and safety profile support further study of talquetamab in monotherapy and in combination approaches for patients with few options for treatment."

Investigators identified the RP2D of 405 µg/kg SC and concluded subcutaneous treatment may provide an opportunity for less frequent dosing than the intravenous formulation. A response was observed in 6/9 triple-class refractory patients and 2/2 penta-drug refractory patients. Pharmacokinetic results indicate target exposure levels at the RP2D. At the RP2D of 405 µg/kg SC, pharmacodynamic data demonstrate consistent T-cell activation, cytokine production and redistribution.

Patients received talquetamab at doses of 1–180 µg/kg with IV administration and 5–800 µg/kg for the SC formulation. Results from the Phase 1 study showed responses in patients who were treated with talquetamab across dose groups; median time to first confirmed response across all doses was one month (range, 0.2–3).4

The Phase 1 study enrolled patients (n=157) with multiple myeloma who had progressed on, or could not tolerate, any available established therapies. Patients had received a median of six prior lines of treatment (range, 2-20); 87 percent were refractory to the last line of therapy, 82 percent were triple-class refractory, and 33 percent were penta-drug refractory to two or more immunomodulatory agents, two or more PIs, and an anti-CD38 therapy. The study is conducted in two parts: dose escalation (part 1) and dose expansion (part 2).4

In the Phase 1 study, adverse events (AEs) at the RP2D which occurred with a Grade 3 frequency of ≥25 percent among the SC cohort were neutropenia (42 percent). With SC dosing, cytokine release syndrome (CRS) was observed in 64 percent of patients and was low-grade with no Grade 3 or greater CRS events at the RP2D. CRS occurred at a median of two days after dosing, and median duration of CRS was also two days. The incidence of neurotoxicity was five percent at the RP2D, with no patients experiencing Grade 3 or greater events with SC dosing.4

"GPRC5D is a novel target in the treatment of multiple myeloma and, as a bispecific antibody that engages T-cells by also targeting CD3, talquetamab is emerging as a potential therapeutic option for heavily pretreated patients," said Yusri Elsayed, M.D., MHSc., Ph.D., Vice President, Global Head, Hematologic Malignancies, Janssen Research & Development, LLC. "Based on the preliminary efficacy, safety, pharmacokinetic and pharmacodynamic data presented today, we are committed to fully exploring the promise of talquetamab in multiple myeloma."

About Talquetamab
Talquetamab is a first-in-class investigational bispecific antibody targeting both GPRC5D, a novel multiple myeloma target, and CD3, the T-cell receptor.4 CD3 is involved in activating T-cells and GPRC5D is highly expressed on multiple myeloma cells.4,5,6 Results from preclinical studies in mouse models demonstrate that talquetamab induces T-cell-mediated killing of GPRC5D-expressing multiple myeloma cells through the recruitment and activation of CD3-positive T-cells and inhibits tumor formation and growth.6

Talquetamab is currently being evaluated in a Phase 1/2 clinical study for the treatment of relapsed or refractory multiple myeloma and is also being explored in combination studies. The development of the antibody followed Janssen Biotech, Inc.’s licensing agreement with Genmab for use of its DuoBody technology platform.*

*DuoBody is a registered trademark of Genmab A/S.

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.7,8 When damaged, these plasma cells rapidly spread and replace normal cells with tumors in the bone marrow. In 2020, it is estimated that more than 32,000 people will be diagnosed and close to 13,000 will die from the disease in the U.S.9 While some patients with multiple myeloma have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.10