Genmab and Incyte to test petosemtamab with KRAS G12D inhibitor in first‑line mCRC
- Phase 1/2 study will evaluate petosemtamab plus INCB161734 and standard‑of‑care chemotherapy in first‑line KRAS G12D‑mutated metastatic colorectal cancer.
- Petosemtamab is an investigational IgG1 bispecific targeting EGFR and LGR5; INCB161734 is an investigational, selective oral KRAS G12D inhibitor.
- Genmab will conduct the study; Incyte will co‑fund the trial and supply clinical drug product of INCB161734.
- KRAS mutations occur in approximately 40% of colorectal cancers; the G12D allele is cited as a common KRAS mutation and is associated with poor prognosis.
Collaboration and study scope
Genmab and Incyte will run a Phase 1/2 clinical trial testing petosemtamab in combination with INCB161734 plus standard‑of‑care chemotherapy as a first‑line treatment for patients with KRAS G12D‑mutated metastatic colorectal cancer. Genmab will conduct the study while Incyte will co‑fund and provide clinical supply of INCB161734.
Rationale and patient population
The programme targets a high‑need subgroup: the article notes KRAS mutations occur in about 40% of colorectal cancers and identifies G12D as a prevalent KRAS allele associated with poor prognosis. The trial will evaluate whether pairing distinct mechanisms—LGR5‑targeted EGFR inhibition and direct KRAS G12D inhibition—alongside chemotherapy can improve outcomes in this population.
Investigational agents and related trials
Petosemtamab is an investigational IgG1‑based bispecific antibody that engages EGFR and LGR5, inhibiting EGFR signaling, promoting EGFR degradation in LGR5‑expressing cancer stem‑like cells, and enhancing innate immune activity; it is also being studied in Phase 3 trials in RAS/BRAF wild‑type mCRC. INCB161734 is an investigational selective ON/OFF KRAS G12D small molecule currently in global development, including the Phase 3 DAWN‑303 study in untreated KRAS G12D pancreatic ductal adenocarcinoma (NCT07522073) and an open‑label Phase 1 across KRAS G12D solid tumours (NCT06179160).
Source: Genmab