On April 30, 2024 Genmab A/S (Nasdaq: GMAB) and Pfizer Inc. (NYSE: PFE) reported that the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for TIVDAK (tisotumab vedotin-tftv) for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy (Press release, Pfizer, APR 30, 2024, View Source [SID1234643134]). This FDA action converts the September 2021 accelerated approval of TIVDAK to a full approval. TIVDAK is the first antibody-drug conjugate (ADC) with demonstrated overall survival data to be granted full FDA approval in this patient population.

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The approval is based on results from the global, randomized, Phase 3 innovaTV 301 clinical trial (NCT04697628), in which TIVDAK met its primary endpoint of overall survival (OS) in patients with previously treated recurrent or metastatic cervical cancer compared to chemotherapy. Secondary endpoints of progression-free survival (PFS) and a confirmed objective response rate (ORR) were also met. In October 2023, results from the innovaTV 301 study were initially disclosed during the Presidential Symposium at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress.

"As a treating physician, it is encouraging to see overall survival data among these patients and a manageable safety profile with tisotumab vedotin," said Brian Slomovitz, M.D., Director of Gynecologic Oncology and Co-Chair of the Cancer Research Committee at Mount Sinai Medical Center, Miami Beach. "Treatment options for patients with advanced or recurrent cervical cancer are limited. The five-year survival rate for patients who have metastatic disease at diagnosis is less than 20% in the U.S.i There is a high unmet need for more treatment options that have demonstrated survival benefit in the contemporary treatment landscape. The approval of tisotumab vedotin brings us a step closer to fulfilling that need."

The innovaTV 301 study met its primary endpoint of OS, demonstrating a 30% reduction in the risk of death compared with chemotherapy (Hazard ratio [HR]: 0.70 [95% CI: 0.54, 0.89], two-sided p=0.0038ii). Median OS for patients treated with TIVDAK was 11.5 months [95% CI: 9.8-14.9] versus chemotherapy 9.5 months [95% CI: 7.9-10.7]. 

"The full FDA approval of TIVDAK represents a significant achievement for women with recurrent and metastatic cervical cancer, reinforcing TIVDAK as a treatment option that has proven to extend survival in patients whose disease has advanced after initial treatments," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "This milestone underscores the importance of our ongoing clinical development program to assess the full potential of tisotumab vedotin as a treatment option in other indications."

"Recurrent or metastatic cervical cancer is a particularly devastating and mostly incurable disease, and patients are in need of survival-extending treatment options," said Chris Boshoff, M.D., Ph.D., Chief Oncology Officer, Executive Vice President at Pfizer. "Today’s full approval by the FDA reinforces the important role of TIVDAK for these patients, as the first antibody-drug conjugate with statistically significant prolonged overall survival data."

The safety profile of TIVDAK in innovaTV 301 was consistent with its known safety profile as presented in the U.S. prescribing information which includes a BOXED WARNING for Ocular Toxicity. No new safety issues were identified. The most common (≥25%) adverse reactions, including laboratory abnormalities, in patients receiving TIVDAK were hemoglobin decreased (41%), peripheral neuropathy (38%), conjunctival adverse reactions (37%), aspartate aminotransferase increased (34%), nausea (33%), alanine aminotransferase increased (30%), fatigue (28%), sodium decreased (27%), epistaxis (26%), and constipation (25%).

The sBLA application received a Priority Review Designation, which is granted by the U.S. FDA to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists.iii TIVDAK was granted accelerated approval in the U.S. by the FDA in September 2021, based on tumor response and durability of response from the innovaTV 204 pivotal Phase 2 single-arm clinical trial evaluating TIVDAK as a monotherapy in patients with previously treated recurrent or metastatic cervical cancer.

"Today marks a great day for patients, especially adults battling advanced cervical cancer," said Tamika Felder, cervical cancer patient advocate and Founder and Chief Visionary Officer, Cervivor, Inc. "This full approval opens up new treatment paths for this patient community who have long faced limited options."

About Cervical Cancer
Cervical cancer remains a disease with high unmet need despite advances in effective vaccination and screening practices to prevent and diagnose pre-/early-stage cancers for curative treatment. Recurrent and/or metastatic cervical cancer is a particularly devastating and mostly incurable disease; up to 15% of adults with cervical cancer present with metastatic disease at diagnosisiv,v and, for adults diagnosed at earlier stages who receive treatment, up to 61%vi will experience disease recurrence. It was estimated that in 2023, more than 13,960 new cases of invasive cervical cancer were diagnosed in the U.S. and 4,310 adults would die from the disease.vii

About the innovaTV 301 Trial
The innovaTV 301 trial (NCT04697628) is a global, 1:1 randomized, open-label Phase 3 trial evaluating TIVDAK (tisotumab vedotin-tftv) versus investigator’s choice of single agent chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan or pemetrexed) in 502 patients with recurrent or metastatic cervical cancer who received one or two prior systemic regimens in the recurrent or metastatic setting.

Patients with recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma or adenosquamous histology, and disease progression during or after treatment with chemotherapy doublet +/- bevacizumab and an anti-PD-(L)1 agent (if eligible) are included. The primary endpoint was overall survival. The main secondary outcomes were progression-free survival and objective response rate.

The study was conducted by Seagen, which was acquired by Pfizer in December 2023, in collaboration with Genmab, European Network of Gynaecological Oncological Trial Groups (ENGOT, study number ENGOT cx-12) and the Gynecologic Oncology Group (GOG) Foundation (study number GOG 3057), as well as other global gynecological oncology cooperative groups. For more information about the Phase 3 innovaTV 301 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

About TIVDAK (tisotumab vedotin-tftv)
TIVDAK (tisotumab vedotin-tftv) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Pfizer’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 suggest that the anticancer activity of tisotumab vedotin-tftv 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-tftv also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

On April 29, 2024 INmune Bio, Inc. (NASDAQ: INMB) (the "Company"), a clinical-stage immunology company focused on developing treatments that harness the patient’s innate immune system to fight disease, reported to advance its Natural Killer (NK) cell therapy, INKmune, in a Phase I/II trial for men with metastatic castration-resistant prostate cancer (mCRPC) (Press release, INmune Bio, APR 29, 2024, View Source [SID1234642472]). The Company is pleased to announce the successful completion of the first cohort in the trial. Following review by the Safety Review Committee (SRC), approval has been granted to proceed with the second dose level (cohort 2). The first patient of the second cohort has been identified and will undergo screening to prepare for treatment.

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So far, there have been 9 administrations of INKmune in the mCRPC study given as an out-patient with no significant adverse events. When added to the experience with INKmune given in the MDS/AML trial, over 20 infusions of INKmune have been given safely without the need for conditioning therapy, pre-medication, or cytokine support.

"We are pleased with the safety of INKmune in men with mCRPC and feedback from the SRC to proceed with cohort 2. Our initial focus is on assessing the safety of INKmune in this group of patients, and the fact that the drug can be safely administered on an outpatient basis is appealing to both patients and clinical teams. Safety is just one aspect of the therapeutic process. The main objective of INKmune therapy is to transform resting NK cells into memory-like NK cells capable of attacking the tumor. Given that prostate cancer has numerous resting NK cells in the tumor microenvironment (TME) that do not eliminate cancer, we believe that INKmune, by transforming the patient’s NK cells into cancer-killing cells, could potentially be an optimal therapy for prostate cancer," said Prof. Mark Lowdell Ph.D., CSO of INmune Bio and inventor of INKmune.

About CaRe PC

CaRe PC is an open label Phase I/II trial that will test up to three doses of INKmune in men with mCRPC. INKmune is given in the out-patient setting via an intravenous infusion three times in the first two weeks of treatment (days 1, 8 and 15). No pre-medication or additional cytokines are needed for INKmune therapy. The patient is followed for six months with careful study of immunologic and anti-cancer responses to INKmune treatment. Immune responses include changes in numbers of tumor killing memory-like NK cells in the patient’s blood and how long these specialized NK cells remain in the circulation. Anti-tumor responses will be monitored by following the level of prostatic surface antigen (PSA) in the blood. Additionally, we will leverage Artificial Intelligence (AI) to quantify the number and size of metastatic lesions using piflufolastat F 18 – a PSMA (prostate-specific membrane antigen) imaging agent developed by Lantheus marketed as Plarify, and by measuring circulating tumor DNA (ctDNA) in the blood. Up to 30 patients will receive one of three levels of dose of INKmune (low, medium, high).

The study uses a novel modified Bayesian design that allows for a 3×3 dose escalation design. Once the Phase I portion is complete, the doses that are safe will be tested simultaneously in the Phase II portion of the trial. Up to 10 patients can be enrolled at each dose level. There are two primary goals of the trial. The first is to demonstrate the safety of INKmune in the patient population, – men with mCRPC. The second is to determine which dose of INKmune should be used in a blinded, randomized registration trial. Determining the best dose of INKmune to use in future clinical trials will depend on a combination of immunologic and anti-tumor responses seen in the men treated with INKmune therapy.

The Company has manufactured all planned doses of INKmune, and these have already been released for the entirety of the Phase 1 study. Assays have already been qualified to Phase 2 standard, and the Company has planned the process for BLA-standard validation in 2025.

About INKmune

INKmune is an NK cell targeted therapy that is not an NK cell. INKmune is a product designed to improve the function of the patient’s own NK cells. INKmune is a patented, pharmaceutical-grade, replication-incompetent human tumor cell line which conjugates to resting NK cells and delivers multiple, essential priming signals, akin to treatment with at least three cytokines in combination. INKmune is stable at -80oC and is delivered by a simple IV infusion. The INKmune:NK interaction ligates multiple activating and co-stimulatory molecules on the NK cell and enhances its avidity of binding to tumor cells; notably those resistant to normal NK-mediated lysis. These INKmune-primed NK cells can lyse a wide variety of NK-resistant tumors including leukemias, lymphomas, myeloma and solid tumors including prostate, renal cell, ovarian, nasopharyngeal, lung and breast cancer. INKmune therapy does not require any type of conditioning, pre-medication, or cytokine support.

On April 29, 2024 Bonum Therapeutics, a biotechnology company that is using its proprietary platform for conditional regulation to create highly active and less toxic medicines, reported that it will present data on a new class of protein therapeutics with the potential for increased safety and efficacy in a wide range of biologic targets and disease areas (Press release, Bonum Therapeutics, APR 29, 2024, View Source [SID1234642449]). Scientists from Bonum will present two posters at the upcoming Keystone Symposium, "Antibodies as Drugs: The Art in Antibody Engineering," which will be held May 5-8 at the Beaver Run Conference Center in Breckenridge, CO.

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"A novel method for generating regulated cytokine therapeutics: Safety and activity of a conditionally active cLAG3-IL2 in a simple antibody format."

"We are excited about the success of our platform technology with multiple conditionally active target/effector combinations, and we are particularly encouraged by the rapid progress of our lead program, cLAG3-IL2," said John Mulligan, PhD, Bonum’s CEO and founder. "These presentations detail the strengths of Bonum’s platform technology and its application to the company’s lead asset."

Details of the poster presentations are as follows:

Title: "Development of a new class of targeted and conditional cytokine therapeutics using a novel dual-binding antibody-based platform."

Abstract: This poster will highlight Bonum’s unique dual-binding antibody platform technology which allows the generation of therapeutics with targeted, conditional cytokine activity only when bound to a selected marker. While the company’s current focus is on the development of therapeutics incorporating immunostimulatory cytokines, its technology can be applied to the regulation of any functional protein moieties, including agonist and antagonistic antibody binding domains, growth factors, and receptors.

Title: "A novel method for generating regulated cytokine therapeutics: Safety and activity of a conditionally active cLAG3-IL2 in a simple antibody format."

Abstract: This poster will highlight a conditionally active therapeutic called cLAG3-IL2, which targets IL-2 to LAG-3+ cells while remaining systemically inert, even at high treatment doses. The in vivo safety and efficacy data described in this poster demonstrate that this program is suitable for clinical development.

The conference organizers have selected Bonum’s poster on its cLAG3-IL2 program for presentation as a short talk during the session "Orchestrating Immune Defense Against Cancer by Antibody Engineering" on May 7 from 8 a.m. to 11 a.m. Dr. Mulligan will give the talk, titled "A novel method for generating regulated cytokine therapeutics: Safety and activity of a conditionally active cLAG3-IL2 in a simple antibody format."

The posters will be available on the Bonum website on Monday, May 6, at noon Mountain Time.

Bonum is developing new therapies based on its proprietary platform of conditionally active therapeutics. The company is a spinout of Good Therapeutics, which developed the technology that Bonum is advancing. The merits of the platform were validated by the Roche acquisition of Good Therapeutics for its PD-1-regulated IL-2 program in September 2022.

On April 29, 2024 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported that responses regarding the status of the Corrective and Preventive Actions (CAPAs) plan have been submitted to the U.S. Food and Drug Administration (FDA) (Press release, Carsgen Therapeutics, APR 29, 2024, View Source [SID1234642448]). This submission is related to the observations identified in the Form 483 issued after the FDA inspection in December 2023 of our clinical manufacturing site in Durham, North Carolina. All relevant works are progressing smoothly according to the previously committed timetable.

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The Company is committed to working closely with the FDA to prioritize quality in production during clinical trials.

On April 29, 2024 Medivir AB (NASDAQ: MVIR) (STO: MVIR), a pharmaceutical company focused on developing innovative treatments for cancer in areas of high unmet medical need, reported that an abstract for the combination of fostroxacitabine bralpamide (fostrox) + Lenvima in hepatocellular carcinoma (HCC) has been accepted for presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Gastrointestinal (GI) Cancers Congress in June 26-29, 2024 in Munich (Press release, Medivir, APR 29, 2024, View Source;lenvima-in-hcc-at-esmo-gi-302129837.html [SID1234642447]).

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The abstract, titled "Liver pharmacodynamics in an open-label phase Ib/IIa study of fostroxacitabine bralpamide (fostrox, MIV-818) in combination with lenvatinib in 2L/3L hepatocellular carcinoma" will be presented at the conference by Dr Hong Jae Chon, CHA Bundang Medical Center in Korea. Dr Chon is one of the investigators in the ongoing phase Ib/IIa study.

The presentation will include pharmacodynamic data from patients in the ongoing phase Ib/IIa clinical study with fostrox + Lenvima combination, evaluating the impact on normal liver function and DNA damage in tumor cells vs healthy cells. The presentation will also include an update on efficacy endpoints as the study has continued to mature and patients have been able to stay on treatment.

The poster will be available on Medivir’s website after the presentation.