Genmab and Incyte agree to colorectal cancer combination trial

A planned first-line colorectal cancer study will pair petosemtamab with a mutation-targeting drug and chemotherapy, as Genmab A/S NASDAQGMAB announced a collaboration with Incyte on Saturday. The Phase 1/2 trial extends petosemtamab’s development to cancers carrying the KRAS G12D mutation.

Under the Oct. 24 collaboration, Genmab will conduct the study, while Incyte Corporation NASDAQINCY will co-fund it and supply its experimental drug INCB161734. The companies did not disclose the cost split, a payment amount or a trial start date.

Genmab is a Copenhagen-based international biotechnology company developing antibody medicines for cancer and other serious diseases.

Genmab’s U.S. depositary shares closed at US$43.79 on Nasdaq at 4:00 p.m. EDT on Oct. 23, according to Google Finance NASDAQGMAB. Incyte closed at US$115.71 on Nasdaq at 4:00 p.m. EDT on Oct. 23, according to Google Finance NASDAQINCY. Both closes preceded the collaboration announcement and cannot establish a market reaction to it.

Petosemtamab Reaches A Different Mutation Group

The proposed regimen combines petosemtamab, which targets EGFR and LGR5, with Incyte’s oral KRAS G12D inhibitor and standard-of-care chemotherapy. It is intended for patients whose metastatic colorectal cancer carries that mutation and who have not received first-line treatment. In the Oct. 24 release, the companies estimate that KRAS mutations occur in approximately 40 per cent of colorectal cancers. They put the G12D mutation’s share at approximately 15 per cent of colorectal cancers.

The release does not identify the chemotherapy backbone, planned patient count, control arm, dosing schedule or primary endpoint. It provides no efficacy or safety results for the proposed combination and reports no FDA feedback on its design.

Genmab says petosemtamab inhibits EGFR signalling and promotes degradation of that receptor in cancer stem-like cells expressing both EGFR and LGR5. The collaboration will investigate whether adding KRAS G12D inhibition and chemotherapy can produce a useful treatment combination; the announcement supplies no clinical evidence that it does.

“This collaboration supports our broader development strategy for petosemtamab as we explore its potential across treatment settings and in novel combinations,” Genmab chief development officer Judith Klimovsky said in the release.

Petosemtamab is already being evaluated with chemotherapy in two Phase 3 colorectal cancer trials in first- and second-line RAS/BRAF wild-type disease, according to the release. The new collaboration adds a mutation-defined population distinct from those studies, while remaining at an earlier development stage.

For Incyte, the agreement adds an antibody partner to INCB161734’s development program. Its drug is already being studied in the enrolling Phase 3 DAWN-303 trial with chemotherapy for previously untreated KRAS G12D-mutated pancreatic cancer, the companies said.

KRAS Developers Test Combination Regimens

Revolution Medicines, Inc. NASDAQRVMD is pursuing another KRAS G12D combination strategy. In its July 2 update, it described the ongoing Phase 3 RASolute 305 trial of zoldonrasib plus chemotherapy against placebo plus chemotherapy in previously untreated metastatic pancreatic cancer.

That program provides development context for Incyte’s pancreatic cancer work, but involves a different cancer from the newly announced colorectal study. The collaboration release offers no comparison against competing KRAS inhibitors.

The iShares Biotechnology ETF NASDAQIBB closed at US$207.74 at 4:00 p.m. EDT on Oct. 23, according to Google Finance. That sector close also preceded the announcement.

The next scheduled evidence checkpoint is Incyte’s Oct. 25 ESMO presentation, abstract 1007RO, on INCB161734 alone or with cetuximab in advanced or metastatic colorectal cancer. Those findings will describe activity and safety with a different antibody regimen; the petosemtamab combination still awaits a disclosed start date.