Researchers participating in GI14-186, a Hoosier Cancer Research Network study for patients with metastatic colorectal cancer (mCRC), recently reported their findings in the journal Cancer Immunology, Immunotherapy.

The single-arm phase Ib study, led by researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, tested the hypothesis that the addition of pembrolizumab to modified FOLFOX6 (mFOLFOX6), an established therapy for mCRC, could safely and effectively improve patient outcomes. The main purpose of the study was to determine median progression free survival (mPFS). Secondary objectives included disease assessments for objective response rate, disease control rate, and delayed response rate; disease assessment per immune related response criteria; overall survival (OS); and safety and tolerability.

Thirty patients with advanced colorectal cancer participated in the study. Patients received concurrent pembrolizumab and mFOLFOX6. The study included a safety run-in for the first six patients. Due to incidences of grade 3 and grade 4 neutropenia in the safety lead-in, the dose of mFOLFOX6 was reduced in the expansion cohort.

Peripheral blood was collected at baseline and during treatment to assess immunological impact. The levels of soluble factors were measured via bioplex, while a panel of checkpoint molecules and phenotypically defined cell populations were assessed with flow cytometry and correlated with RECIST and mPFS.

Median PFS for subjects was 8.8 months and median OS was not reached at data cutoff. Best responses of stable disease, partial response, and complete response were observed in 43.3%, 50.0%, and 6.7% of patients, respectively.

Researchers found that the primary endpoint was not superior to historic control and immunosuppressive myeloid and T cell subsets that were analyzed were not associated with response. However, several soluble and cellular immune biomarkers were associated with improved RECIST and mPFS, and researchers noted these biomarkers may be informative for future regimens combining chemotherapy with immune checkpoint inhibitors.

Study authors include: Cameron J. Herting¹, Matthew R. Farren¹, Yan Tong², Ziyue Liu², Bert O’Neil², Tanios Bekaii-Saab³, Anne Noonan⁴, Christopher McQuinn⁴, Thomas A. Mace⁴, Walid Shaib¹, Christina Wu¹, Bassel F. El-Rayes¹, Safi Shahda², and Gregory B. Lesinski¹; ¹Winship Cancer Institute of Emory University, ²IU Melvin and Bren Simon Comprehensive Cancer Center, ³Mayo Clinic (Scottsdale, Arizona), and ⁴The Ohio State University Comprehensive Cancer – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

The study was supported by Merck Sharpe & Dohme Corp.

See abstract.

About Hoosier Cancer Research Network:

Hoosier Cancer Research Network (formerly known as Hoosier Oncology Group) conducts innovative cancer research in collaboration with academic and community physicians and scientists across the United States. The organization provides comprehensive clinical trial management and support, from conception through publication. Created in 1984 as a program of the Walther Cancer Institute, Hoosier Cancer Research Network became an independent nonprofit clinical research organization in 2007. Since its founding, Hoosier Cancer Research Network has conducted more than 230 trials in a variety of cancer types and supportive care, resulting in more than 350 publications. More than 9,000 subjects have participated in Hoosier Cancer Research Network clinical trials.