On May 19, 2021 Apexigen, Inc., a clinical-stage biopharmaceutical company focused on discovering and developing a new generation of antibody therapeutics for oncology, reported the presentation of clinical data from the Parker Institute for Cancer Immunotherapy’s Phase 2 clinical trial evaluating sotigalimab, Apexigen’s monoclonal antibody targeting CD40, in combination therapy for patients with metastatic pancreatic cancer at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting, being held virtually June 4-8, 2021 (Press release, Apexigen, MAY 19, 2021, View Source [SID1234590991]). Sotigalimab, Apexigen’s lead immuno-oncology therapeutic, is a potentially first-in-class and best-in-class CD40 agonist, with unique epitope specificity and Fc receptor engagement for optimal therapeutic effect and tolerability.
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"These important new data will play a critical role in our development plans for sotigalimab," said Xiaodong Yang, M.D., Ph.D., Chief Executive Officer of Apexigen. "We were thrilled to partner with the Parker Institute for Cancer Immunotherapy, Cancer Research Institute and Bristol Myers Squibb, providing our potential best-in-class CD40 therapeutic for their pancreatic cancer study to help address one of the greatest outstanding challenges in oncology. We are encouraged by the clinical benefit observed with the novel combination regimen of sotigalimab and standard of care gemcitabine/nab-paclitaxel. We believe the improvements observed in one-year overall survival, while not statistically significant as compared to the historical standard-of-care control, may provide meaningful benefit in a subset of patients with pancreatic cancer."
Dr. Yang continued, "Beyond these promising data, we are particularly encouraged by the pharmacodynamic effects of sotigalimab. These include an increase in activated myeloid dendritic cells and M1 macrophages, which demonstrates the on-mechanism and differentiated activity of sotigalimab. In addition, the identification of a unique biomarker signature that was associated with clinical benefit of treatment with sotigalimab plus chemotherapy may play a critical role in guiding our clinical strategy, as well as enabling the identification and selection of patients most likely to benefit from sotigalimab. Based on these clinical and biomarker data, we expect an additional Phase 2 trial with more patients and a biomarker-based patient selection strategy may be needed before launching a Phase 3 trial in this indication. We look forward to leveraging these important learnings in our ongoing and future studies, building upon our foundation of compelling single-agent activity in immunotherapy-naïve melanoma, durable activity in PD-1 refractory melanoma, and promising activity in our target combinations of chemotherapy and/or radiation in other solid tumors. To maximize the full therapeutic potential of sotigalimab, we have implemented a broad and comprehensive clinical development strategy and are currently conducting several Phase 2 trials across indications, lines of therapies and combination settings, from which we anticipate multiple milestones and near-term data readouts."
The poster titled, "Gemcitabine and nab-Paclitaxel ± Nivolumab ± CD40 Agonistic Monoclonal Antibody Sotigalimab (APX005M) in Participants with Untreated Metastatic Pancreatic Adenocarcinoma: Phase 2 Final Results", will be presented by Mark O’Hara, M.D., an assistant professor of Medicine, in the division of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania (Abstract #4019; Track: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary). The poster has been selected for presentation as part of a Poster Discussion Session from 9:00-10:00 a.m. ET on Friday, June 4, 2021. The poster will also be available on-demand through the ASCO (Free ASCO Whitepaper) conference portal, starting at 9:00 a.m. ET.
Summary of the data:
The Phase 2 study evaluated multiple novel combination regimens on top of standard of care gemcitabine/nab-paclitaxel (Gem+NP) in three cohorts: Cohort A1 (Gem+NP+Nivolumab), Cohort B2 (Gem+NP+Sotigalimab 0.3 mg/kg), and cohort C2 (Gem+NP+Nivolumbab+Sotigalimab 0.3 mg/kg). Each cohort was designed to be compared against a historical control OS.
The primary endpoint was 1-year overall survival (OS) as compared to the historical control standard of care (Gem+NP) of 35%. The one-year OS was 57.3% for A1 (P=0.007, n=34), 48.1% for B2 (P=0.062, n=36), and 41.3% for C2 (P=0.236, n=35). Improvements in OS were statistically significant for cohort A1, with moderate clinical activity observed in cohort B2
Safety profiles across all three cohorts were manageable and consistent with previously reported Phase 1b data, suggesting sotigalimab may be well tolerated when utilized in multiple combination therapy strategies
An increase of activated myeloid dendritic cells (CD86+ mDC) was found in the patients treated with sotigalimab containing regimens (Cohorts B2 and C2)
An increase of tumoral M1 macrophages was found only in patients treated with sotigalimab+chemotherapy (Cohort B2)
Lower baseline levels of effector memory CD8+ T cells, exhausted effector memory CD4+ T cells and TNF and MYC gene expression were associated with improved survival with sotigalimab+chemotherapy (Cohort B2)
Additional biomarker results from the Phase 2 study will be presented in a poster titled, "Baseline level and early on-treatment clearance of circulating mutant KRAS in metastatic pancreatic ductal adenocarcinoma treated with chemotherapy with or without immunotherapy", to be presented by Jacob Till, M.D., Ph.D., Senior Research Investigator, at Penn. (Abstract #4122; Track: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary).
About the Phase 1b/2 Clinical Trial
In the Phase 1b portion of this open-label, multicenter Phase 1b/2 clinical trial, previously untreated patients with metastatic pancreatic ductal adenocarcinoma received sotigalimab 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 Phase 2 portion of the trial evaluated multiple combination regimens on top of standard of care gemcitabine/nab-paclitaxel (Gem+NP): Gem+NP plus sotigalimab, Gem+NP plus nivolumab and Gem+NP plus sotigalimab and nivolumab. The primary endpoint was 1-year overall survival (OS) rate compared with a 35% historical rate for Gem+NP. Secondary endpoint results included safety (adverse events [AEs], treatment-related adverse events [TRAEs]), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and duration of response (DOR). Exploratory endpoints included immune pharmacodynamics, associations between tumor and immune biomarkers and clinical outcomes, and baseline and on-treatment microbiome profiles. For additional information on this trial (NCT03214250), please visit www.clinicaltrials.gov.
About Sotigalimab (APX005M)
Sotigalimab is a novel, humanized monoclonal antibody that stimulates the anti-tumor immune response. Sotigalimab targets CD40, a co-stimulatory receptor that is essential for activating both innate and adaptive immune systems. Binding of Sotigalimab to CD40 on antigen presenting cells (i.e., dendritic cells, monocytes and B-cells) initiates a multi-faceted immune response bringing multiple components of the immune system (e.g., T cells, macrophages) to work in concert against cancer. Sotigalimab is currently in Phase 2 clinical development for the treatment of cancers such as pancreatic cancer, esophageal and gastroesophageal junction cancers, melanoma, non-small cell lung cancer, rectal cancer and sarcoma in various combinations with immunotherapy, chemotherapy, radiation therapy or a cancer vaccine. Additional information on clinical trials for Sotigalimab can be found at www.clinicaltrials.gov.