Novel immunotherapy combinations in highly malignant ovarian cancer

First patients dosed in phase 2 platform clinical trial testing

Currently, the majority of ovarian cancers – upwards of 75 percent – are of the subtype “high grade serous carcinoma,” which is the type being treated in this phase 2 study. While most patients with this malignant ovarian cancer subtype initially respond to standard cytotoxic therapies, more than 80 percent will relapse and succumb to the disease within five years. New treatments are urgently needed for this deadliest of gynecological cancers, which is diagnosed in more than a quarter-million women worldwide each year according to World Health Organization estimates.

CCTG study lead Helen MacKay, MBChB, B.Sc., MRCP, M.D
CCTG study lead Helen MacKay, MBChB, B.Sc., MRCP, M.D

This phase 2 trial titled, “Immunotherapy Platform Study in Platinum Resistant High Grade Serous Ovarian Cancer (IPROC)” (NCT04918186), is sponsored by CRI clinical partner the Canadian Cancer Trials Group (CCTG), and is open and actively recruiting patients to sites in Canada and, in the second half of 2022, will open sites in the United States. Overall, up to 60 patients are planned to be enrolled in this platform study with up to 40 patients in these two initial cohorts.

“We are excited to move forward in partnership with CRI, OCRA, and our collaborators with this important study. IPROC’s innovative trial design means that we can accelerate the pace of discovery in understanding how to optimize immunotherapy for the treatment of patients diagnosed with ovarian cancer,” said CCTG study lead Helen MacKay, MBChB, B.Sc., MRCP, M.D.This clinical trial is using an adaptive platform study design that utilizes a single master protocol that allows for multiple treatments to be evaluated in different groups of patients, or cohorts, from the same patient population. Such a study design offers flexibility in that different treatments can be evaluated in different cohorts, treatment regimens can be modified between cohorts, and treatment selection criteria can be customized for a specific cohort.

Immunotherapy as monotherapy in treating patients with this aggressive type of ovarian cancer has not resulted in improvement in patient outcomes. In contrast, a recent randomized Phase 2 trial led by Dmitriy Zamarin, M.D., Ph.D., a member of the Cancer Research Institute Drug Selection Committee and study chair on the IPROC platform trial, demonstrated a three-fold improvement in overall response rates among ovarian cancer patients treated with a combination of immunotherapies compared to patients treated with a single immunotherapy.

“The IPROC trial builds upon the results seen in positive immunotherapy combination studies in ovarian cancer, and was designed in collaboration with our partners to explore each patient’s immunological response to determine which combinations result in the greatest patient benefit and why they are more effective than other combinations,” said Jay Campbell, managing director of the Anna-Maria Kellen Clinical Accelerator and Venture Fund at the Cancer Research Institute.

Patients with high grade serous ovarian cancer that is refractory or resistant to platinum-based cytotoxic therapy will be assigned to one of two cohorts testing novel immunotherapy combinations with drugs supplied by AstraZeneca and BioAtla, Inc.: Cohort A will receive AstraZeneca’s PD-L1-blocking antibody durvalumab (IMFINZI®) in combination with BioAtla’s BA3011 (mecbotamab vedotin), a conditionally active antibody-drug conjugate targeting AXL, a receptor tyrosine kinase that is overexpressed across many solid tumor types, while Cohort B will receive durvalumab in combination with BioAtla’s BA3021 (ozuriftamab vedotin), a conditionally active antibody-drug conjugate targeting ROR2, another receptor tyrosine kinase that is overexpressed in solid tumors. As part of the eligibility evaluation process, patients will be screened for expression levels of AXL or ROR2 and eligible patients will be assigned to the appropriate cohort accordingly.

“Ovarian cancer patients are in dire need of additional treatment options, and partnering with the Cancer Research Institute on this innovative platform trial is a crucial step in our efforts to hasten drug development,” said Audra Moran, president and CEO of Ovarian Cancer Research Alliance. “This collaboration allows OCRA to have a direct impact on future outcomes for our patients as well as add to the collective understanding of this disease.”