On October 24, 2026 Genmab A/S (Nasdaq: GMAB) and Incyte (Nasdaq: INCY) reported a clinical trial collaboration to evaluate petosemtamab, Genmab’s investigational IgG1-bispecific antibody targeting the epidermal growth factor receptor (EGFR) and leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5), in combination with INCB161734, Incyte’s investigational, potent and selective KRAS G12D inhibitor, and standard-of-care chemotherapy as a first-line treatment for patients with metastatic colorectal cancer harboring a KRAS G12D mutation, an area with substantial unmet medical need.
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"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. "Partnering with Incyte enables us to evaluate this investigational combination in patients with KRAS G12D-mutated metastatic colorectal cancer, reflecting our commitment to research collaborations aimed at expanding potential treatment options for more patients."
"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. "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."
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.
KRAS mutations occur in approximately 40% of colorectal cancers, with G12D being the most common KRAS mutation. These cancers are associated with poor prognosis, underscoring the need for new treatment approaches. The collaboration reflects a shared focus on investigating whether agents with distinct and potentially complementary mechanisms, combined with standard-of-care chemotherapy, may offer a path toward a new treatment option for patients with KRAS G12D-mutated metastatic colorectal cancer.
About Petosemtamab (GEN1158)
Petosemtamab is an investigational human IgG1-based bispecific antibody targeting the EGFR and the LGR5 and designed to support multiple anti-tumor mechanisms. 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. Petosemtamab is also engineered to enhance innate immune-mediated activity through interactions with macrophages and natural killer cells. 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. Please visit View Source for more information.
About INCB161734
INCB161734 is an investigational, novel, selective and orally bioavailable small molecule ON/OFF KRAS G12D inhibitor. KRAS is one of the most frequently altered oncogenic drivers across solid tumors, and 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 pancreatic ductal adenocarcinoma (PDAC) to further evaluate the efficacy and safety of INCB161734 in combination with standard-of-care (SoC) chemotherapy.
INCB161734 is also being evaluated as a monotherapy and in combination with standard-of-care (SoC) chemotherapy (gemcitabine/nab-paclitaxel [GEMNabP] or modified FOLFIRINOX [mFOLFIRINOX]), in an ongoing open-label Phase 1 study across KRAS G12D-mutated solid tumors (NCT06179160).
(Press release, Genmab, OCT 24, 2026, View Source [SID1234673779])