On March 31, 2019 Apexigen, Inc., a clinical-stage biopharmaceutical company, reported the presentation of new clinical data on APX005M in combination therapy in patients with metastatic pancreatic cancer (Press release, Apexigen, MAR 31, 2019, View Source [SID1234534792]). The data are being presented in a plenary session today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place March 29 – April 3, 2019 in Atlanta, GA, by Parker Institute for Cancer Immunotherapy (PICI) researchers at the University of Pennsylvania. Apexigen’s lead immuno-oncology (I-O) therapeutic, APX005M, a monoclonal antibody targeting CD40, is being evaluated in multiple clinical trials in different types of solid tumors.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In an interim analysis of an ongoing Phase 1b clinical trial, 20 of 24 evaluable patients with metastatic pancreatic cancer demonstrated tumor shrinkage following treatment with APX005M in combination with standard-of-care chemotherapy, with or without Bristol-Myers Squibb’s PD-1 inhibitor nivolumab. Several patients remained on therapy after one year of treatment.

"Our CD40 agonist APX005M is critical for activating the body’s innate and adaptive immunity, potentially enabling the immune system to fight even the most difficult-to-treat forms of cancer," said co-author Ovid Trifan, M.D., Ph.D., Chief Medical Officer and Senior Vice President of Clinical Development of Apexigen. "We are encouraged by these interim results and are excited to see this trial advance to the next phase in evaluating a novel combination therapy for patients with metastatic pancreatic cancer. In addition to these results, we look forward to a second presentation of clinical data at AACR (Free AACR Whitepaper) tomorrow on APX005M in combination therapy for patients with metastatic or unresectable melanoma who have progressed on anti-PD-1/PD-L1 therapy. We are committed to advancing a broad clinical development program for APX005M in multiple types of cancer as we work toward transforming the standard of care for patients across a wide range of cancer indications."

First author Mark H. O’Hara, M.D., Assistant Professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania, commented, "In this interim analysis of this trial, we are encouraged by the safety and activity signals from anti-CD40 immunotherapy APX005M in combination with chemotherapy with or without checkpoint inhibition as a new approach to treating metastatic pancreatic cancer. Given that most patients with metastatic pancreatic cancer have evidence of progression of their cancer within about 5 months of starting first line chemotherapy, seeing several patients stay on treatment on this trial for more than one year is exciting. We look forward to exploring the benefits of CD40 activation to treat this aggressive form of cancer."

About the Phase 1b/2 Clinical Trial
In the Phase 1b portion of the clinical trial, previously untreated patients with metastatic pancreatic ductal adenocarcinoma received APX005M in combination with gemcitabine and nab-paclitaxel, a standard-of-care chemotherapy regimen for this patient population, and half of the patients also received Bristol-Myers Squibb’s PD-1 inhibitor nivolumab. The combination therapy treatment was well-tolerated. Several patients remained on treatment for about a year, and had a durable response. 20 of 24 evaluable patients demonstrated tumor shrinkage. The trial has progressed to the Phase 2 portion.

For additional information on this trial (NCT03214250), please visit www.clinicaltrials.gov.

APX005M Data Presentations at AACR (Free AACR Whitepaper) 2019 Annual Meeting
Plenary Session Presentation Title: A Phase 1b Study of CD40 Agonistic Monoclonal Antibody APX005M Together with Gemcitabine (Gem) and nab-Paclitaxel (NP) with or without Nivolumab (Nivo) in Untreated Metastatic Ductal Pancreatic Adenocarcinoma (PDAC) Patients (Abstract #CT004)
Presenter: Mark O’Hara, M.D., Assistant Professor of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Plenary Session Date and Time: Sunday, March 31, 2019 2:25 PM – 2:45 PM ET
Plenary Session: Clinical Trials Plenary Session 1
Location: Georgia World Congress Center, Building A, Marcus Auditorium

Late-breaking Abstract Title: Phase Ib/II clinical trial of CD40 agonistic antibody APX005M in combination with nivolumab (nivo) in subjects with metastatic melanoma (M) or non-small cell lung cancer (NSCLC) (Abstract #CT089)
Poster Session Date and Time: Monday, April 1, 2019 1:00 PM – 5:00 PM ET
Poster Session: Phase 1 Clinical Trials
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 16

About APX005M
APX005M is a humanized monoclonal antibody designed to stimulate the anti-tumor immune response. APX005M targets CD40, a co-stimulatory receptor that is essential for activating both innate and adaptive immune systems. Binding of APX005M to CD40 on antigen presenting cells (i.e., dendritic cells, monocytes and B-cells) is believed to initiate a multi-faceted immune response that enables multiple components of the immune system (e.g., T cells, macrophages) to work in concert against cancer. APX005M is currently in Phase 2 clinical development for the treatment of cancers such as pancreatic cancer, melanoma, esophageal and gastroesophageal junction cancers, non-small cell lung cancer, renal cell carcinoma, sarcomas, and pediatric brain cancer in various combinations with immunotherapy, a cancer vaccine, chemotherapy or radiation therapy. Additional information on clinical trials for APX005M can be found at www.clinicaltrials.gov.

On March 30, 2019 Maverick Therapeutics Inc., a private biopharmaceutical company pioneering next-generation redirected T-cell targeted immunotherapies, reported that it will unveil pre-clinical data characterizing its novel COBRATM therapeutic platform at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 being held from March 29 to April 3 in Atlanta, Georgia (Press release, Maverick Therapeutics, MAR 30, 2019, View Source [SID1234534787]). COBRA is the most advanced bispecific T-cell engaging platform in its class, designed to safely target solid tumors with highly specific and potent activity. These pre-clinical data characterize the conditional and potent activity of the COBRATM platform in vitro as well as demonstrate the regression of established solid tumors in in vivo models.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

COBRATM is a proprietary approach to cancer immunotherapy. The COBRATM molecules are designed to bind to a specific target but are engineered to activate only after they enter the tumor microenvironment, allowing for specific T-cell engagement and activation at the site of the cancer. Focusing T-cell activation and killing at the tumor site is ideal for the treatment of solid tumors, which account for 90% of all cancers1. COBRATM molecules include a component that extends their half-life in the circulation prior to activation within the tumor site; once activated, this component is lost, allowing the active molecules to then be cleared from the body more rapidly after targeting and killing the cancer cells. This further increases their safety window by reducing the potential for active COBRATM molecules to travel outside the tumor to healthy tissues and cause damage.

"We are encouraged by the inaugural data on our proprietary COBRATM platform, as they provide proof-of-concept for our approach to overcome the challenges current T-cell engagers face when addressing solid tumors," said Maverick Therapeutics Chief Executive Officer Jim Scibetta. "With its scientifically elegant design, COBRATM has the potential to deliver increased specificity, higher potency and reduced toxicity, all of which may help extend both the duration and quality of life of people living with solid tumor cancers."

Full abstracts are available online at View Source Details of the poster presentation are listed below.

Title: COBRATM: A Novel Conditionally Active Bispecific Antibody that Regresses Established Solid Tumors in Mice
Session Title: Immunology – Therapeutic Antibodies 1
Abstract Number: 557
Poster Board Number: 21
Presentation Time: Sunday, March 31, 1pm – 5pm ET
Location: Georgia World Congress Center – Exhibit Hall B, Poster Section 23

About COBRA Therapeutic Platform

The company’s proprietary COBRA, or COnditional Bispecific Redirected Activation, therapeutic platform is the most advanced bispecific T-cell engagement platform, designed to target solid tumors with highly potent and specific activity, while avoiding damage to normal healthy tissues. COBRATM molecules are designed to bind to a specific target, but are engineered to activate only after they enter the tumor microenvironment, allowing for specific T-cell engagement and activation at the site of the cancer. COBRATM molecules include a component that extends their presence in the circulation prior to activation within the tumor site; once activated this component is lost, allowing the active molecule to then be cleared from the body more rapidly after targeting and killing the cancer cells. This increases their safety window by reducing the potential for active COBRA molecules to escape the tumor and travel to healthy tissues.

On March 29, 2019 Seattle Genetics, Inc. (Nasdaq:SGEN) reported completion of enrollment in the potentially pivotal innovaTV 204 phase 2 clinical trial evaluating the efficacy, safety and tolerability of tisotumab vedotin as monotherapy for patients with recurrent and/or metastatic cervical cancer who have relapsed or progressed after standard of care treatment (Press release, Seattle Genetics, MAR 29, 2019, View Source [SID1234534761]). Tisotumab vedotin is being developed in collaboration with Genmab A/S. The innovaTV 204 trial is intended to support potential registration under the U.S. Food and Drug Administration’s (FDA) accelerated approval regulations. Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) designed to target Tissue Factor antigen on cancer cells and deliver the cell-killing agent monomethyl auristatin E (MMAE) directly inside cancer cells. Tissue Factor is overexpressed in cervical cancer and many other solid tumors.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Cervical cancer is a devastating disease with a significant need to develop improved therapies for patients with metastatic disease who have progressed after treatment," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "Completing enrollment in this potentially pivotal phase 2 trial marks an important step forward in evaluating tisotumab vedotin for women with previously treated recurrent and/or metastatic cervical cancer."

For more information about the phase 2 innovaTV 204 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

About innovaTV 204 Trial

The innovaTV 204 trial (also known as GCT1015-04) is an ongoing single-arm, global, multicenter study of tisotumab vedotin for patients with recurrent and/or metastatic cervical cancer who progressed on or relapsed after treatment with doublet chemotherapy used alone or in combination with bevacizumab (Avastin). The study enrolled over 100 patients at multiple centers. The primary endpoint of the trial is objective response rate as assessed by blinded independent central review. Key secondary endpoints include duration of response, progression-free survival, overall survival, safety and tolerability.

On March 29, 2019 Bicycle Therapeutics, a biotechnology company pioneering a new class of therapeutics based on its proprietary bicyclic peptide (Bicycle) product platform, reported that Bicycle scientists have been selected to present two oral presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Atlanta (Press release, Bicycle Therapeutics, MAR 29, 2019, View Source [SID1234534762]). These presentations will focus on preclinical programs that have shown target-dependent anti-tumor activity across a range of patient-derived Nectin-4 and EphA2 expressing cancer models.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Because of their small size and profound efficacy, Bicycle’s toxin conjugates are able to do what many previous antibody drug conjugate approaches could not," said Nicholas Keen, Ph.D., Chief Scientific Officer of Bicycle Therapeutics. "Preclinical data from both our BT5528 and BT8009 programs show target-dependent anti-tumor activity across a range of EphA2-expressing and Nectin-4-expressing cancer models, respectively, and we’re proud that AACR (Free AACR Whitepaper) has chosen to highlight our work."

In addition, Bicycle has also been selected to present a poster on its CD137 program, intended to activate cytotoxic T-cells, a type of cell used in the body’s immune response.

Added Keen: "We believe Bicycle’s work on CD137 has produced the first fully-synthetic immune oncology modulators, which may confer several advantages over existing modalities because of the multivalency and pharmacokinetic characteristics of Bicycles."

Details on Bicycle’s presentations at the 2019 AACR (Free AACR Whitepaper) Annual Meeting are as follows:

Oral Presentation Title: BT8009: A bicyclic peptide toxin conjugate targeting Nectin-4 (PVRL4) displays efficacy in preclinical tumor models
Presenter: Michael Rigby, Ph.D., project leader for BT8009, a Nectin-4 targeted Bicycle Toxin Conjugate
Session Title: Novel Therapeutics
Abstract: #4479
Date and Time: April 2, 2019, 3:00 p.m. – 5:00 p.m. EDT

Oral Presentation Title: BT5528, an EphA2-targeting Bicycle Toxin Conjugate (BTC): Profound efficacy without bleeding and coagulation abnormalities in animal models
Presenter: Gavin Bennett, Ph.D., Director of Preclinical Development and project leader for BT5528, an EphA2 targeted Bicycle Toxin Conjugate
Session Title: Novel Therapeutics
Abstract: #4481
Date and Time: April 2, 2019, 3:00 p.m. – 5:00 p.m. EDT

Poster Presentation Title: Activation of CD137 using multivalent and tumor-targeted Bicyclic peptides
Presenter: Johanna Lahdenranta, Ph.D., Director of In Vivo Pharmacology
Session Title: Novel Immunomodulatory Agents 1
Abstract: #3257
Date and Time: April 2, 2019, 8:00 a.m. – 12:00 p.m. EDT

On March 29, 2019 CEL-SCI Corporation (NYSE American: CVM) reported that the Independent Data Monitoring Committee (IDMC) for the Company’s pivotal Phase 3 head and neck cancer study of its investigational immunotherapy Multikine* (Leukocyte Interleukin, Injection) has completed its recent review of the Phase 3 study data (Press release, Cel-Sci, MAR 29, 2019, View Source [SID1234534763]). The data from all 928 enrolled patients were provided to the IDMC by the clinical research organization (CRO) responsible for data management of this Phase 3 study.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The IDMC made the following recommendation:

The IDMC recommendation is to continue the trial until the appropriate number of events have occurred.
IDMCs are committees commonly used by sponsors of clinical trials to protect the interests of the patients and the integrity of the study data in ongoing trials, especially when the trials involve patients with life threatening diseases, and when, as in cancer clinical trials, they extend over long periods of time.