Incyte, the Wilmington, Delaware-based biopharmaceutical company, will pair its investigational KRAS G12D inhibitor with an investigational antibody from Copenhagen-based Genmab in a new study for patients with metastatic colorectal cancer (mCRC). The companies announced on October 24, 2026 a clinical trial collaboration to test Incyte’s INCB161734 with Genmab’s petosemtamab and standard-of-care chemotherapy. The study will focus on first-line treatment of mCRC with the KRAS G12D mutation.
“Metastatic colorectal cancer remains difficult-to-treat, underscoring the importance of evaluating novel combinations grounded in complementary scientific approaches with the potential to enhance efficacy,” said Pablo J. Cagnoni, M.D., President, Incyte and Global Head of Research and Development.
Inside the Study
Genmab will run the Phase 1/2 study, evaluating the three-part combination in patients who have not yet received treatment for KRAS G12D-mutated mCRC. Incyte will co-fund the study and supply INCB161734. Financial terms were not disclosed.
The combination brings together two different ways of attacking the cancer. INCB161734 blocks the mutated KRAS G12D protein that drives tumor growth. Petosemtamab is a bispecific antibody that targets two proteins on cancer cells: the epidermal growth factor receptor (EGFR) and leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5).
“Our collaboration with Genmab 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 metastatic colorectal cancer,” Dr. Cagnoni said.
For Genmab, the study fits a wider plan to test petosemtamab in new settings:
“This collaboration supports our broader development strategy for petosemtamab as we explore its potential across treatment settings and in novel combinations,” said Judith Klimovsky, M.D., Executive Vice President and Chief Development Officer, Genmab.
Why KRAS G12D Matters
KRAS mutations occur in about 40% of colorectal cancers, according to the release. G12D is the most common of those mutations, found in about 15% of all colorectal cancer cases. Cancers with KRAS mutations are associated with a poor prognosis.
Where Each Drug Stands
INCB161734 is an investigational, oral small molecule that inhibits KRAS G12D in both its active (“ON”) and inactive (“OFF”) states. It is in the global Phase 3 DAWN-303 study (NCT07522073), which is enrolling patients with previously untreated KRAS G12D-mutated pancreatic ductal adenocarcinoma (PDAC). The KRAS G12D mutation occurs in about 40% of PDAC cases, according to Incyte. INCB161734 is also in an ongoing Phase 1 study across KRAS G12D-mutated solid tumors (NCT06179160), both alone and with chemotherapy.
Petosemtamab (GEN1158) is an investigational antibody designed to block EGFR signaling, trigger EGFR breakdown in cancer stem-like cells that carry both EGFR and LGR5, and boost the activity of immune cells such as macrophages and natural killer cells. It is being studied in head and neck squamous cell carcinoma (HNSCC) and other solid tumors. It is also in two Phase 3 trials with chemotherapy in first- and second-line metastatic colorectal cancer without RAS or BRAF mutations.
About Incyte
Incyte is a global biopharmaceutical company that discovers, develops, and commercializes medicines across three franchises: hematology, oncology, and inflammation and autoimmunity, including dermatology. Headquartered in Wilmington, Delaware, it has operations across Europe, North America, and Japan.
About Genmab
Founded in 1999, Genmab is an international biotechnology company focused on antibody medicines for cancer and other serious diseases. Its work spans bispecific antibodies, antibody-drug conjugates (ADCs), and immune-modulating antibodies. Genmab says its science powers eight approved antibody medicines. The company has operations across North America, Europe, and the Asia Pacific region.
