On June 6, 2022 Seagen Inc. (Nasdaq: SGEN) and Genmab A/S (Nasdaq: GMAB) reported interim data from the innovaTV 205 trial, which included data evaluating tisotumab vedotin (TIVDAK)in combination with pembrolizumab (Cohort E) in patients with recurrent or metastatic cervical cancer (r/mCC) who have not received prior systemic therapy, with a confirmed objective response rate (ORR) of 41% (95% Confidence Interval [CI]: 24% to 59%) and median durability of response that was not reached within almost 19 months of median follow up (Press release, Seagen, JUN 6, 2022, View Source [SID1234615621]). Data were presented during an oral session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting on June 6.

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"These data showed encouraging and durable anti-tumor activity and provide rationale for the continued development of tisotumab vedotin (TV) in front-line recurrent or metastatic cervical cancer, including its potential use as part of triplet or quadruplet combination therapy," said Domenica Lorusso, M.D., Ph.D., a gynecologic oncologist working at the Gynaecology Oncology Unit of Policlinico Gemelli IRCCS of Rome and an investigator of the innovaTV 205 clinical trial. "These early results from multiple expansion cohorts of innovaTV 205 support our continued efforts to investigate TV as part of combination therapy to further improve treatment response and durability for this group of patients with high unmet need."

Dose expansion Cohort E enrolled 33 patients with recurrent or metastatic cervical cancer who had not received any prior systemic therapy. At the time of data cutoff, the confirmed ORR among 32 evaluable patients was 41% (95% Confidence Interval [CI], range 24% to 59%), with 16% of patients (n=5) achieving complete responses and 25% of patients (n=8) achieving partial responses. Median duration of response (DOR) was not reached. Median progression-free survival (PFS) was 5.3 months (95% CI: 4.0 to 12.2).

Building on data presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021, additional longer-term follow-up data from Cohorts D (tisotumab vedotin in combination with carboplatin in previously untreated patients) and Cohort F (tisotumab vedotin in combination with pembrolizumab in previously treated patients) of the innovaTV 205 trial were also included in the ASCO (Free ASCO Whitepaper) 2022 oral presentation.

In Cohort E, the most common treatment-emergent adverse events (TEAEs) were alopecia (61%), diarrhea (55%), epistaxis (49%), conjunctivitis (45%), and nausea (46%). Prespecified adverse events (AEs) of interest (grade 1-2/grade ≥3) with tisotumab vedotin included ocular (58%/9%), peripheral neuropathy (49%/3%), and bleeding (61%/6%).

Tisotumab vedotin in combination with pembrolizumab across lines of treatment (Cohorts E/F), and with carboplatin (Cohort D) in first-line, demonstrated a tolerable and manageable safety profile. Across all three cohorts, no new safety signals were reported outside of known adverse events associated with the individual agents.

Tisotumab vedotin is approved for treatment of patients with previously treated recurrent or metastatic cervical cancer in the US and is commercialized under the tradename TIVDAK. See TIVDAK U.S. Important Safety Information, including Boxed Warning, below.

"With Genmab, we will continue to investigate tisotumab vedotin in combination with other therapies because there is still an unmet need for more effective first-line treatment for advanced cervical cancer patients," said Marjorie Green, M.D., Senior Vice President and Head of Late-Stage Development, Seagen. "We’re also researching innovative new tools to help increase awareness of the disparities and unmet needs that cervical cancer patients experience in order to better support this community in the future."

One highlight of real-world studies presented is a poster discussion on the Cervical Cancer Geographical Burden Analyzer. This is an open access, web-based, interactive tool to visualize geographical areas in the US where cervical cancer education or healthcare resource needs are high.

"The Cervical Cancer Geographical Burden Analyzer has potential to help expand understanding of cervical cancer disease burden across different communities," said Tara Castellano, M.D., Gynecologic Oncologist at Louisiana State University’s Department of Gynecologic Oncology and lead investigator for research and development of the Cervical Cancer Geographical Disease Burden Analyzer. "This tool may be particularly useful for researchers, policy makers, and advocacy groups to inform allocation of healthcare resources."

Additional updates from the tisotumab vedotin clinical development program were presented at the ASCO (Free ASCO Whitepaper) 2022 Annual Meeting, including trial-in-progress overviews for innovaTV 205/ENGOT-cx8/GOG-3024 evaluating first-line tisotumab vedotin in combination with pembrolizumab, carboplatin and bevacizumab in first-line r/mCC; and for innovaTV 207 Part D evaluating tisotumab vedotin in combination with pembrolizumab and platinum in squamous cell carcinoma of the head and neck (HNSCC) and squamous cell non-small cell lung cancer (sqNSCLC).

"The collective data presented for tisotumab vedotin at the ASCO (Free ASCO Whitepaper) 2022 Annual Meeting are reflective of our commitment to investigating this therapy across treatment lines and in combination with other therapies," said Jan van de Winkel, Ph. D., Chief Executive Officer, Genmab. "With Seagen, we are continuing to advance clinical trials in order to explore future treatment options for recurrent or metastatic cervical cancer patients."

About the innovaTV 205 Trial

The innovaTV 205 trial (also known as ENGOT-cx8/GOG-3024) is a Phase 1b/2 open-label, multi-center trial of tisotumab vedotin monotherapy and in combination with bevacizumab, pembrolizumab, or carboplatin in patients with recurrent or metastatic cervical cancer. The study consists of two parts: dose escalation (Cohorts A, B, and C) and dose expansion (Cohorts D, E, F, G and H). Patients enrolled in the dose escalation cohorts have progressed during or after standard of care therapy or are intolerant or ineligible to receive standard of care treatments. The primary objective is to identify and establish the maximum tolerated dose and Recommended Phase 2 Dose (RP2D) of tisotumab vedotin as combination therapy. Within the dose expansion cohorts, patients with recurrent or metastatic cervical cancer who have not previously received prior systemic therapy are treated in Cohorts D, E and H, with patients who have progressed on or after standard of care treatments evaluated in Cohorts F and G.For more information about the innovaTV 205 clinical trial and the study collaborators, please visit www.clinicaltrials.gov (Identifier: NCT03786081).

About Tisotumab Vedotin

Tisotumab vedotin-tftv (TIVDAK) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Seagen’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggests that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

In September 2021, the U.S. Food and Drug Administration granted accelerated approval for tisotumab vedotin-tftv (TIVDAK) in adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. TIVDAK is the first and only approved ADC for the treatment of these patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. The ongoing clinical trial innovaTV 301, an open-label, randomized, global trial, is intended as the confirmatory trial for use in verifying and describing the clinical benefit and as support for US and global regulatory applications.

Indication

TIVDAK is indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information

BOXED WARNING: OCULAR TOXICITY

TIVDAK caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration. Conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care before, during, and after infusion. Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity.

Warnings and Precautions

Ocular Adverse Reactions occurred in 60% of patients with cervical cancer treated with TIVDAK across clinical trials. The most common were conjunctival adverse reactions (40%), dry eye (29%), corneal adverse reactions (21%), and blepharitis (8%). Grade 3 ocular adverse reactions occurred in 3.8 % of patients, including severe ulcerative keratitis in 3.2% of patients. One patient experienced ulcerative keratitis with perforation requiring corneal transplantation. Cases of symblepharon were reported in patients with other tumor types treated with TIVDAK at the recommended dose. In innovaTV 204, 4% of patients experienced visual acuity changes to 20/50 or worse including 1% of patients who experienced a visual acuity change to 20/200. Of the patients who experienced decreased visual acuity to 20/50 or worse, 75% resolved, including the patient who experienced decreased visual acuity to 20/200.

Refer patients to an eye care provider for an ophthalmic exam including visual acuity and slit lamp exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care to reduce the risk of ocular adverse reactions. Promptly refer patients to an eye care provider for any new or worsening ocular signs and symptoms. Withhold dose, reduce the dose, or permanently discontinue TIVDAK based on the severity of the adverse reaction.

Peripheral Neuropathy (PN) occurred in 42% of cervical cancer patients treated with TIVDAK across clinical trials; 8% of patients experienced Grade 3 PN. PN adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (11%), peripheral sensorimotor neuropathy (5%), motor neuropathy (3%), muscular weakness (3%), and demyelinating peripheral polyneuropathy (1%). One patient with another tumor type treated with TIVDAK at the recommended dose developed Guillain- Barre syndrome. Monitor patients for signs and symptoms of neuropathy. For new or worsening PN, withhold, dose reduce, or permanently discontinue TIVDAK based on the severity of PN.

Hemorrhage occurred in 62% of cervical cancer patients treated with TIVDAK across clinical trials. The most common all grade hemorrhage adverse reactions were epistaxis (44%), hematuria (10%), and vaginal hemorrhage (10%). Grade 3 hemorrhage occurred in 5% of patients. Monitor patients for signs and symptoms of hemorrhage. For patients experiencing pulmonary or CNS hemorrhage, permanently discontinue TIVDAK. For Grade ≥2 hemorrhage in any other location, withhold until bleeding has resolved, blood hemoglobin is stable, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage recurrence. After resolution, either resume treatment or permanently discontinue TIVDAK.

Pneumonitis: Severe, life-threatening, or fatal pneumonitis can occur in patients treated with antibody-drug conjugates containing vedotin, including TIVDAK. Among patients with cervical cancer treated with TIVDAK across clinical trials, 2 patients (1.3%) experienced pneumonitis, including 1 patient who had a fatal outcome.

Monitor patients for pulmonary symptoms of pneumonitis. Infectious, neoplastic, and other causes for symptoms should be excluded through appropriate investigations.

Withhold TIVDAK for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue TIVDAK in all patients with Grade 3 or 4 pneumonitis.

Embryo-Fetal Toxicity: TIVDAK can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TIVDAK and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TIVDAK and for 4 months after the last dose.

Adverse Reactions

In the innovaTV 204 clinical trial (n=101), serious adverse reactions occurred in 43% of patients; the most common (≥3%) were ileus (6%), hemorrhage (5%), pneumonia (4%), PN, sepsis, constipation, and pyrexia (each 3%). Fatal adverse reactions occurred in 4% of patients who received TIVDAK, including septic shock, pneumonitis, sudden death, and multisystem organ failure (each 1%).

Adverse reactions leading to permanent discontinuation occurred in 13% of patients receiving TIVDAK; the most common (≥3%) were PN (5%) and corneal adverse reactions (4%). Adverse reactions leading to dose interruption occurred in 47% of patients; the most common (≥3%) were PN (8%), conjunctival adverse reactions (4%), and hemorrhage (4%). Adverse reactions leading to dose reduction occurred in 23% of patients; the most common (≥3%) were conjunctival adverse reactions (9%) and corneal adverse reactions (8%).

The most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (52%), fatigue (50%), lymphocytes decreased (42%), nausea (41%), PN (39%), alopecia (39%), epistaxis (39%), conjunctival adverse reactions (37%), hemorrhage (32%), leukocytes decreased (30%), creatinine increased (29%), dry eye (29%), prothrombin international normalized ratio increased (26%), activated partial thromboplastin time prolonged (26%), diarrhea (25%), and rash (25%).

Drug interactions

Strong CYP3A4 Inhibitors: Concomitant use with strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E (MMAE) exposure, which may increase the risk of TIVDAK adverse reactions. Closely monitor patients for TIVDAK adverse reactions.

Use in Specific Populations

Moderate or Severe Hepatic Impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Lactation: Advise lactating women not to breastfeed during TIVDAK treatment and for at least 3 weeks after the last dose.

On June 6, 2022 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing first-in-class allogeneic gamma delta chimeric antigen receptor (CAR) T cell therapies for cancer, reported emerging positive safety and efficacy data from the Company’s Phase 1 study of ADI-001 for the potential treatment of relapsed or refractory B-cell Non-Hodgkin’s Lymphoma (NHL) in an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 6, 2022 (Press release, Adicet Bio, JUN 6, 2022, View Source [SID1234615620]). The presentation outlines a summary of clinical data as of a May 31, 2022, data-cut date.

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"Adicet is a pioneer in the field of gamma delta CAR T cell therapies and it is gratifying to see the highly encouraging clinical data for ADI-001 unfold as a potential best-in-class therapy for NHL," said Chen Schor, President and Chief Executive Officer of Adicet Bio. "Notably, with a favorable safety and tolerability profile, treatment to date with ADI-001 demonstrated an impressive CR rate, including 100% in CAR-T relapsed patients, and very encouraging durability of response. We look forward to discussing the data in more detail and outlining next steps in our webcast this afternoon."

"It is impressive to see 50 percent of six-month evaluable patients cancer free beyond seven months. One of these patients had previously relapsed after two treatments with autologous anti-CD19 CAR T and now remains cancer free seven and a half months following administration of ADI-001, suggesting the patient has had major clinical benefit from ADI-001. This is particularly notable because patients who relapse after autologous anti-CD19 CAR T have dismal outcomes with a median survival of approximately six months," said Sattva Neelapu, M.D., Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. "When we look at the totality of these early data, we have an indicator that allogeneic gamma-delta CAR T cell therapy like ADI-001 could be a significant advance."

"NHL remains a disease that is very difficult to treat, especially in high-risk patients with aggressive disease. Our study is enrolling patients with aggressive B-cell lymphoma, including patients with double-hit and triple-hit high-grade B cell lymphoma and patients who had a prior relapse to autologous anti-CD19 CAR T therapy," said Francesco Galimi, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Adicet Bio. "We are encouraged by the CRs observed to date in the Phase 1 study and are committed to rapidly advancing ADI-001 into a potential pivotal program."

Data highlights as of the May 31, 2022 data-cut date included in the ASCO (Free ASCO Whitepaper) presentation are as follows:

Of the eight evaluable patients, three received ADI-001 at dose level 1 (30 million CAR+ cells), three received ADI-001 at dose level 2 (100 million CAR+ cells) and two received ADI-001 at dose level 3 (300 million CAR+ cells). There are currently no patients with indolent lymphoma, such as follicular lymphoma, enrolled in the study.
Patients were heavily pretreated with a median number of prior therapies of 4 (range 2-5) and had a poor prognostic outlook as indicated by the median International Prognostic Index (IPI) score of 4 (range 2-5).
ADI-001 treatment demonstrated a 75% overall response rate (ORR) and complete response (CR) in the study across all dose levels. In dose levels 2 and 3 combined, ADI-001 demonstrated an 80% ORR and CR rate.
In three patients that previously relapsed after prior autologous anti-CD19 CAR T therapy, treatment with ADI-001 demonstrated 100% ORR and CR rate. These patients included a triple-hit high grade B-cell lymphoma patient with prior exposure to Liso-cel, as well as a DLBCL patient and a double-hit high grade B-cell lymphoma patient who had previously achieved a PR to Axi-cel.
Early data indicate encouraging durable anti-tumor responses with potential for dose related increase in durability. 50% (2 of 4) of evaluable patients with at least six months follow up remain cancer free.
Detection of circulating ADI-001 in the blood by flow cytometry indicated in vivo expansion and dose-related increase of ADI-001 exposure in patients.
ADI-001 was well tolerated in the study to date. There were no occurrences of dose-limiting toxicities, graft vs host disease (GvHD), or Grade 3 or higher Cytokine Release Syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) reported. There were no infections associated with enhanced lymphodepletion (eLD).
Table 1: Summary of ADI-001 interim data from three dosing cohorts: *

*Efficacy-evaluable patients as of the May 31, 2022 data-cut date. Data are subject to further review and verification. BOR= best overall response. PD=progressive disease.

Table 2: ADI-001 Preliminary Efficacy Data:
(Per protocol analysis, independent radiographic assessment using Lugano 2014)

*Efficacy-evaluable patients as of the May 31, 2022, data-cut date. Data are subject to further review and verification.

As of the May 31, 2022, data-cut date, of the six patients who achieved CR:

Dose level 1:

As previously disclosed, one patient administered ADI-001 in dose level 1, a 66-year-old female who had achieved a CR, developed COVID-19 related pneumonia approximately two and a half months after ADI-001 administration and later died of complications from it, unrelated to ADI-001. This patient was previously reported as a partial response (PR) by local radiological assessment and has been assessed as a CR by independent central reading.

One patient with triple-hit high grade B-cell lymphoma in dose level 1 who had relapsed following two prior treatments with autologous anti-CD19 CAR T therapy, had a CR after treatment with ADI-001. The patient developed a local skin relapse at four months, and was administered local radiotherapy. The skin lesion resolved with no systemic therapy provided to the patient. The patient continues to be cancer free seven and a half months following administration of ADI-001, as measured by a negative PET/CT scan.

Dose level 2:

Both patients administered ADI-001 in dose level 2 have ongoing CR. One patient has a CR beyond seven months and one patient has a CR beyond four and a half months.

Dose level 3:

Both patients administered ADI-001 in dose level 3 have ongoing CR with follow-up beyond three and one month, respectively.

In summary, 50% of evaluable patients with at least six months follow up (2 of 4) remain cancer free.

Table 3: ADI-001 Preliminary Safety Data in Efficacy-Evaluable Patients+

+Safety assessment was performed using the Common Terminology Criteria for Adverse Events (v5) and the American Society for Transplantation and Cellular Therapy criteria. The two ADI-001-related adverse events of special interest (AESI) were a Grade 1 CRS at DL1 and a Grade 1 ICANS at DL2, which resolved within 24 hours without medical intervention​; No DLTs or GvHD; No treatment discontinuations due to AEs​; two patients administered standard lymphodepletion (sLD) and six patients eLD​; There were no eLD-associated clinical infection.

*One patient in DL 1 who received sLD developed COVID-19 pneumonia later died of complications of it, unrelated to ADI-001.

Given the safety profile to date, the protocol was amended to include a new DL 4 (1E9 CAR+ cells) and a potential ADI-001 consolidation dosing at DL3 to finalize the recommended Phase 2 dose in the second half of 2022. The Company expects to provide at least one additional clinical update for the ADI-001 Phase 1 study in the second half of 2022. The Company will discuss with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) the design of two pivotal intent studies and a potential path to support a Biologics License Application (BLA) and Marketing Authorization Application (MAA) for ADI-001 and initiate at least one potentially pivotal study in the first half of 2023.

Details of the ASCO (Free ASCO Whitepaper) Oral Presentation:

Abstract Number: 7509
Abstract Title: A Phase 1 Study of ADI-001: Anti-CD20 CAR-engineered Allogeneic Gamma Delta (γδ) T cells in Adults with B-cell Malignancies
Presenting Author: Sattva Neelapu, M.D., The University of Texas MD Anderson Cancer Center
Session Type/Title: Clinical Science Symposium/ Beating Bad Blood: The Power of Immunotherapy in Hematologic Malignancies
Date: Monday, June 6, 2022
Time: 8:00 AM-9:30 AM CDT

Webcast/ Conference Call information

The Company will host a conference call and webcast today, June 6, 2022, at 4:30pm ET to discuss the results. The live webcast of the presentation can be accessed under "Presentations & Events" in the investors section of the Company’s website at www.adicetbio.com or by dialing (877) 800-3802 (domestic) or +1 (615) 622-8057 (international) and referencing the conference ID 5466375. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

About ADI-001

ADI-001 is an investigational allogeneic gamma delta CAR T cell therapy being developed as a potential treatment for relapsed or refractory B-cell NHL. ADI-001 targets malignant B-cells via an anti-CD20 CAR and via the gamma delta innate and T cell endogenous cytotoxicity receptors. Gamma delta T cells engineered with an anti-CD20 CAR have demonstrated potent anti-tumor activity in preclinical models, leading to long-term control of tumor growth. In April 2022, ADI-001 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the potential treatment of relapsed or refractory B-cell NHL.

About the GLEAN Study

This Phase 1 study is an open-label, multi-center study of ADI-001 enrolling adults diagnosed with B-cell malignancies who have either relapsed, or are refractory to at least two prior regimens. The primary objectives of the study are to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ADI-001, and to determine optimal dosing as a monotherapy. The study is expected to enroll approximately 75 patients. For more information about the clinical study design, please visit www.clinicaltrials.gov (NCT04735471).

On June 6, 2022 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported it will host an investor webcast on Friday, June 10, 2022 at 8:00am ET (2:00pm CEST) to discuss initial clinical data from its on-going Phase 2 APEX trial evaluating bezuclastinib in patients with Advanced Systemic Mastocytosis being presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress (Press release, Cogent Biosciences, JUN 6, 2022, View Source [SID1234615619]).

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The event will be led by Andrew Robbins, Cogent’s President and CEO, and will include a presentation by Daniel J. DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute. The speakers and additional members of Cogent leadership will be available during the Question and Answer session.

The webcast will be accessible through the Investors and Media section of Cogent’s website at www.cogentbio.com. Following the live webcast, an archived replay will also be available.

On June 6, 2022 Artiva Biotherapeutics, Inc., an oncology company whose mission is to deliver highly effective, off-the-shelf allogeneic natural killer (NK) cell therapies that are safe and accessible to cancer patients, reported the appointment of Thorsten Graef, M.D., Ph.D., as Chief Medical Officer (Press release, Artiva Biotherapeutics, JUN 6, 2022, View Source [SID1234615617]). As a highly respected drug development leader, Dr. Graef brings to Artiva more than a decade of experience building and managing clinical development organizations, global multidisciplinary groups and cross-functional teams.

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"I am delighted to welcome Thorsten to our team. He brings substantive expertise to Artiva, including having led the development of IMBRUVICA through its registration in a number of indications, coupled with his recent experiences in the NK cell therapy space," stated Fred Aslan, MD, CEO of Artiva. "He joins Artiva as we transition from being a company with a single clinical trial to one with potentially multiple trials in both hematopoietic and solid tumor indications where we hope to demonstrate the clinical impact of allogeneic, off-the-shelf, NK cell therapies."

"I was impressed by Artiva’s Manufacturing-First approach and pragmatic development program choices," stated Dr. Graef. "NK cell therapies are making good clinical progress, but to achieve registration and commercial success, therapies will also need to be truly off-the-shelf and cost-effective with a scalable process in place. This is where I believe Artiva’s investments in manufacturing can strengthen and accelerate our development plans."

Most recently, Dr. Graef served as Chief Medical Officer at Acepodia USA, with responsibility for all of the company’s research and clinical development activities. Prior to his role at Acepodia, he served as Vice President of Oncology Early Development at AbbVie Inc., overseeing clinical activities, including the development and regulatory preparations of 20+ clinical assets. In addition, he held a series of senior leadership roles, including Head of Global Clinical Development, at Pharmacyclics LLC before and after AbbVie Inc.’s acquisition of the company in May of 2015, where he led the development of IMBRUVICA (ibrutinib). Prior to Pharmacyclics, Dr. Graef served as medical director of Merck Research Lab, Oncology at Merck & Co., Inc.

Prior to his time in the life sciences industry, Dr. Graef was an attending physician in the hematology, oncology, and immunology department at the University Hospital of Düsseldorf in Germany. He received his M.D. in internal medicine and his Ph.D. in molecular medicines from Heinrich-Heine University Medical School in Düsseldorf and completed his postdoctoral research fellowship at the Stanford University School of Medicine. Dr. Graef has published more than 50 original peer-reviewed publications, including many in top journals, such as NEJM, Lancet, Blood, PNAS, and Journal of Experimental Medicine.

On June 6, 2022 ImmunityBio, Inc. (NASDAQ: IBRX), a leading clinical-stage immunotherapy company, reported new positive data from the company’s pivotal Phase 2/3 trial for BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in situ (QUILT 3032) and Phase 2 trial in advanced pancreatic cancer (QUILT 88) (Press release, ImmunityBio, JUN 6, 2022, View Source [SID1234615616]). The results, which were presented during the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, demonstrate the strong and diverse growth of ImmunityBio’s immunotherapy platform that includes an IL-15 superagonist (N-803), adenovirus vaccine platform, and engineered off-the-shelf natural killer (NK) cell therapy. Together with the company’s self-amplifying RNA and yeast platforms, and Toll receptor activators, along with clinical progress across a range of highly challenging cancer types and commercial-scale manufacturing capabilities, ImmunityBio believes that it is well positioned to change the paradigm of care in cancer and infectious disease.

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"The theme at this year’s ASCO (Free ASCO Whitepaper) conference finally is about combination therapy and immunotherapy. We have been focused on this approach for the past decade and the trial results we presented at this year’s ASCO (Free ASCO Whitepaper) conference are validation that the approach of harnessing the patient’s immune system with a combination of NK and T-cell activation has clinical benefit," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. "We have, at risk, made the investments to build GMP commercial-scale manufacturing for our platforms and are now positioned to launch QUILT trials in earlier first-line, neoadjuvant and even preventative settings."

The data demonstrate a potential new option for BCG-unresponsive non-muscle invasive bladder cancer patients who were treated with Bacillus Calmette-Guérin (BCG) plus N-803 (Anktiva) and the doubling of historic overall survival rates in patients with advanced pancreatic cancer who were treated with the Nant Cancer Vaccine, N-803 (Anktiva, IL-15 cytokine fusion protein), and off-the-shelf PDL1-targeted high-affinity NK cell (PDL1 t-haNK) infusion.

"Collectively, bladder cancer and pancreatic cancer claim more than half a million lives globally each year, with many patients failing to respond to the current standards of care," said Sandeep Bobby Reddy, M.D., Chief Medical Officer at ImmunityBio. "In dozens of studies, we have shown that N-803 proliferates NK and T cells and thus serves as an enhancing secondary boost, augmenting the immunological response when given in combination with BCG or a checkpoint inhibitor. This mechanism of action of inducing trained innate immune memory, through the combination of N-803 and a prime, contributes we believe to the compelling results we’re seeing in these important trials."

The study results presented at ASCO (Free ASCO Whitepaper) are summarized below:

QUILT 3032 BCG-unresponsive NMIBC CIS (Cohort A)
In an oral presentation on June 3, 2022, Principal Investigator Karim Chamie, M.D., Associate Professor of Urology at UCLA, presented the final clinical results of pivotal trial of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive CIS and papillary non-muscle-invasive bladder cancer (Abstract #4508).

Link to video presentation on ecancer.org:

View Source

Excellent safety and tolerability profile of N-803 + BCG for CIS

1% treatment-related SAEs
0% immune-related AEs
0% grade 4 and 5 AE
71% Complete remission (CR) rate at anytime
26.6 months median durable complete remission
96% Avoidance of bladder cancer progression at 24 months in responders
91% Avoidance of cystectomy at 24 months in responders
100% Bladder cancer-specific overall survival at 24 months
Favorable & familiar dosing schedule with activity localized to the bladder
QUILT 3.032 is an open-label, three cohort, multicenter Phase 2/3 study of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) and was opened in 2017. The primary endpoint for Cohort A of this Phase 2/3 study is incidence of complete response (CR) of CIS at any time. The U.S. Food and Drug Administration (FDA) previously granted N-803 Breakthrough Therapy and Fast Track designations when used in combination with Bacillus Calmette-Guerin (BCG) for the treatment of BCG-unresponsive NMIBC CIS. On May 23, 2022, ImmunityBio announced that it had submitted a Biologics License Application (BLA) to the FDA for N-803 plus BCG for the treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in situ (CIS) with or without Ta or T1 disease.

QUILT 88 Pancreatic Cancer
The study results were presented on June 4, 2022 by the Principal Investigator Dr. Tara Seery of Hoag Cancer Center in a poster session titled Phase 2 clinical trial of DAMP inducers combined with IL15 superagonist, N-803, and anti–PD-L1 NK cell therapy more than doubles historical overall survival in patients with third- to sixth-line advanced pancreatic cancer (Abstract #4147, Poster #132).

Nant Cancer Vaccine (NCV) more than doubled median OS versus historical OS (Manax ASCO (Free ASCO Whitepaper) GI 2019) of 3 months after >2L
Median overall survival in 3rd line subjects (n=34) was 6.2 months (95% CI: 4.9, 9.8)
Overall survival for ITT population (N=78) of 3rd, 4th and 5th line is 5.8 months (95% CI: 4.0, 6.9)
Treatment-related (TR) SAEs were uncommon (6%), no TR deaths were reported
All treatments were performed as outpatient
Treatment ongoing for 25 patients
"For the first time, we are seeing clinical efficacy of immunotherapy in pancreatic cancer. Lung, Kidney, Head and Neck cancer, melanoma and many other cancers have been successfully treated with immunotherapy, but pancreatic cancer has been left behind in the revolution. Now, with ImmunityBio’s combination immunotherapy there is renewed hope for patients with this dreaded disease," said Dr. Seery. "We are hopeful to be able to present similar results at future ASCO (Free ASCO Whitepaper) conferences in the other cohorts of this trial in which we continue to enroll patients."

QUILT 88 is a Phase 2, randomized, three-cohort, open-label study evaluating the comparative efficacy and overall safety of standard-of-care chemotherapy versus low-dose chemotherapy in combination with PD-L1 t-haNK, N-803, and aldoxorubicin in subjects with locally advanced or metastatic pancreatic cancer (NCT04390399). Each treatment setting, as well as each first- and second-line or later maintenance treatment, will be evaluated independently as Cohorts A, B, and C, respectively, with Cohorts A and B having independent experimental and control arms. The study is expected to enroll 328 subjects across all three cohorts (63 of 80 participants are currently enrolled in Cohort C, third-line or greater). The primary objective of Cohorts A and B is progression-free survival (PFS) per RECIST V1.1, and the objective of Cohort C is overall survival (OS). Secondary objectives include initial safety and additional efficacy measures, including overall response rate (ORR), complete response (CR) rate, durability of response (DoR), disease control rate (DCR), and overall survival (OS).

Currently, four trial sites have been activated: Hoag Memorial Hospital Presbyterian in Orange County, Calif., The Chan Soon-Shiong Institute for Medicine in Los Angeles County, Calif., Avera McKennan Hospital and University Health Center in Sioux Falls, South Dakota, which serves patients in the tri-state area (Iowa, Nebraska and South Dakota); and Astera Cancer Care, East Brunswick, N.J.