WILMINGTON, DE — Incyte Corp. (Nasdaq: INCY) and Genmab A/S (Nasdaq: GMAB) have agreed to jointly support an early-stage clinical trial combining two experimental cancer drugs with chemotherapy, expanding their efforts to develop a first-line treatment for metastatic colorectal cancer patients carrying the KRAS G12D mutation.
The Phase 1/2 study will evaluate Incyte’s KRAS G12D inhibitor, INCB161734, alongside Genmab’s bispecific antibody petosemtamab and standard-of-care chemotherapy, according to the companies.
Genmab will conduct the trial, while Wilmington-based Incyte will provide its investigational drug and share the study’s costs. Financial terms and a timetable for the trial were not disclosed.
The collaboration targets a molecular subtype of colorectal cancer associated with poor outcomes and limited treatment options.
KRAS mutations occur in approximately 40% of colorectal cancers, with G12D representing the most common variant. The specific mutation is found in approximately 15% of colorectal cancer cases.
The companies aim to determine whether combining therapies that target different cancer-related pathways can improve treatment outcomes when administered alongside chemotherapy.
INCB161734 is an orally administered small-molecule inhibitor designed to block the activity of mutated KRAS G12D, a genetic alteration that drives tumor growth.
Petosemtamab, also known as GEN1158, is an investigational antibody engineered to target two proteins involved in cancer biology: epidermal growth factor receptor, or EGFR, and leucine-rich repeat-containing G-protein-coupled receptor 5, known as LGR5.
The antibody is designed to inhibit EGFR signaling, promote degradation of EGFR in certain cancer stem-like cells and stimulate immune activity involving macrophages and natural killer cells.
By combining the two experimental treatments with chemotherapy, the researchers will investigate whether blocking KRAS-driven tumor signaling and targeting EGFR- and LGR5-related mechanisms can produce complementary anticancer effects.
“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,” Pablo J. Cagnoni, Incyte’s president and global head of research and development, stated.
The collaboration extends Incyte’s clinical development program for INCB161734 beyond pancreatic cancer, where the compound is already being evaluated in advanced studies.
The drug is currently being tested in the global Phase 3 DAWN-303 trial, which is enrolling previously untreated patients with KRAS G12D-mutated pancreatic ductal adenocarcinoma.
The study is examining INCB161734 in combination with standard chemotherapy to assess its effectiveness and safety.
The compound is also undergoing evaluation in an open-label Phase 1 trial involving patients with KRAS G12D-mutated solid tumors, both as a standalone treatment and in combination with chemotherapy regimens including gemcitabine and nab-paclitaxel or modified FOLFIRINOX.
KRAS G12D mutations are present in approximately 40% of pancreatic ductal adenocarcinoma cases, making the alteration an important target in Incyte’s oncology development strategy.
For Genmab, the agreement expands the clinical investigation of petosemtamab into another colorectal cancer population.
The antibody is already being studied in head and neck squamous cell carcinoma and other solid tumors.
Genmab is also evaluating petosemtamab with chemotherapy in two Phase 3 trials involving first- and second-line treatment of metastatic colorectal cancer without RAS or BRAF mutations.
The new collaboration will instead focus specifically on patients whose tumors carry the KRAS G12D mutation, extending the company’s investigation into a genetically distinct group.
“Partnering with Incyte enables us to evaluate this investigational combination in patients with KRAS G12D-mutated metastatic colorectal cancer,” Judith Klimovsky, Genmab’s executive vice president and chief development officer, stated.
Both INCB161734 and petosemtamab remain investigational treatments. The planned study will examine their combined use in patients who have not previously received treatment for metastatic colorectal cancer, with clinical evidence needed to establish the regimen’s safety and potential effectiveness.
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