Genmab and Incyte Collaborate on Clinical Trial for Metastatic Colorectal Cancer

Genmab and Incyte have announced a clinical trial collaboration aimed at evaluating a new treatment approach for patients with metastatic colorectal cancer (mCRC) harboring a KRAS G12D mutation. The Phase 1/2 study will evaluate the investigational IgG1-bispecific antibody, petosemtamab, in combination with Incyte’s investigational KRAS G12D inhibitor, INCB161734, and standard-of-care chemotherapy.

The collaboration is part of Genmab’s broader development strategy for petosemtamab, which targets the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). This combination therapy is designed to address the substantial unmet medical need in patients with KRAS G12D-mutated mCRC, a condition that affects approximately 40% of colorectal cancers, with the G12D mutation being the most common.

The collaboration will explore the potential of combining KRAS G12D inhibition with LGR5-targeted EGFR inhibition and standard-of-care chemotherapy, with the goal of advancing a new first-line treatment approach for patients with KRAS G12D-mutated metastatic colorectal cancer.

Under the collaboration, Genmab will conduct the Phase 1/2 study evaluating petosemtamab in combination with INCB161734 and standard-of-care chemotherapy in patients with KRAS G12D-mutated mCRC in the first-line setting. Incyte will co-fund the study and provide clinical supply of INCB161734.

Petosemtamab, also known as GEN1158, is an investigational human IgG1-based bispecific antibody targeting the EGFR and LGR5. It inhibits EGFR-mediated signaling by engaging a unique site on the receptor to prevent ligand binding. In addition, petosemtamab triggers EGFR degradation in cancer stem-like cells expressing both EGFR and LGR5. It is currently being investigated in head and neck squamous cell carcinoma (HNSCC) and other solid tumors, including colorectal cancer (CRC). Petosemtamab is being evaluated in combination with chemotherapy in two Phase 3 trials in first- and second-line RAS/BRAF wild-type metastatic CRC.

INCB161734 is an investigational, novel, selective, and orally bioavailable small molecule KRAS G12D inhibitor. The KRAS G12D mutation is among the most common KRAS alterations, occurring in approximately 40% of pancreatic ductal adenocarcinoma (PDAC) cases and approximately 15% of colorectal cancer (CRC) cases. INCB161734 is being evaluated in the global Phase 3 DAWN-303 (NCT07522073) study, which is currently enrolling patients with previously untreated KRAS G12D-mutated PDAC to further evaluate the efficacy and safety of INCB161734 in combination with standard-of-care (SoC) chemotherapy.

Incyte is redefining what’s possible in biopharmaceutical innovation. Through deep scientific expertise and a relentless focus on patients, Incyte has built an established portfolio of first-in-class medicines and an extensive portfolio of next-generation medicines across its key franchises: Hematology, Oncology, and Inflammation & Autoimmunity.

Genmab, established in 1999, is an international biotechnology company dedicated to improving the lives of people with cancer and other serious diseases through innovative antibody medicines. For over 25 years, its passionate, innovative, and collaborative team has advanced a broad range of antibody-based therapeutic formats, including bispecific antibodies, antibody, drug conjugates (ADCs), immune-modulating antibodies, and other next-generation modalities. Genmab’s science powers eight approved antibody medicines, and the company is advancing a strong late-stage clinical pipeline, including wholly owned programs, with the goal of delivering transformative medicines to patients.