Study for Evaluation of Murlentamab (GM102) Anti-tumoral Activity in Colorectal Cancers

Colorectal Cancer Clinical Trial

Official title: Open, Non Controlled, Parallel Cohorts, Multicenter, Phase 2A Study for Evaluation of the Antitumor Activity of GM102 Single Agent and in Combination With Chemotherapy in Patients With Locally Advanced Or Metastatic Colorectal Cancer

Status Completed

Clinical Trial Summary

Phase 2A study, assessing the antitumor activity and the safety profile of GM102, a new compound (monoclonal antibody), administered alone or in combination with chemotherapy in patients with locally advanced or metastatic colorectal cancer. The primary objective of the study is to evaluate the antitumor activity of GM102 single agent and in combination with trifluridine/tipiracil.

Clinical Trial Description

GM102 is a humanized low fucose monoclonal antibody with a high affinity to AMHRII receptor (fetal receptor mediating the activity of AMH, reexpressed in a variety of solid tumors). GM102 acts through engagement of immune cells (macrophages, natural killer (NK) cells) to trigger ADCC (antibody dependent cellular cytotoxicity) and phagocytosis of tumor cells. AMRHII expression was found in 73% of primary colorectal tumors tested. Advanced/metastatic colorectal cancer (CRC) remains an unmet need disease, with few therapeutic options beyond two or three lines of therapy. CRC is characterized by a tumor microenvironment (TME) particularly rich in macrophages and more specifically macrophages capable of tumor phagocytosis. The pattern of the TME remains a major prognostic factor in the metastatic setting. C201 consists in two parallel cohorts and an expansion of cohort II for patients with advanced or metastatic colorectal cancer in two different settings of the disease: - Cohort I (GM102 as a single agent) in refractory patients, having exhausted all therapeutic options. Patients will receive GM102 alone at the dose of 7 mg/kg administered by intravenous infusion at Day 1, Day 8, Day 15 and Day 22 of each 28-day cycle - Cohort II (GM102 in combination with trifluridine/tipiracil) in patients candidate to receive single agent trifluridine/tipiracil, after at least two lines of treatment for the advanced or metastatic disease. Patients will receive GM102 at the dose of 7 mg/kg administered by intravenous infusion at Day 1, Day 8, Day 15 and Day 22 and trifluridine/tipiracil at 35 mg/m² per dose twice daily orally administered on Days 1 to 5 and Days 8 to 12 of each 28-day cycle. - Cohort II expansion (GM102 in combination with trifluridine/tipiracil) same as cohort II except a loading dose of 10 mg/kg q1w during 28-day cycle 1 Patients will be treated with GM102 (Cohort I) or GM102 and trifluridine/tipiracil (Cohort II and Cohort II expansion) until confirmed progression or toxicity. A Trial Steering Committee (TSC) will analyze and qualify GM102 activity and toxicities and will provide recommendations on the Investigational Medicinal Product (IMP) continuation. ;

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

• NCT number: NCT03799731
• Study type: Interventional
• Source: GamaMabs Pharma
• Status: Completed
• Phase: Phase 2
• Start date: July 11, 2018
• Completion date: February 10, 2021