One Genmab Rybrevant challenge is rendered moot

Some of the difficulties Genmab might have faced surrounding its work on molecules with mechanistic similarity to Rybrevant have just been averted. That’s because development of one such project, GEN1286, appears to have been discontinued.

GEN1286 was being tested in just one clinical study, and this has ceased recruitment after enrolling just 23 out of a planned 260 solid tumour patients, it has emerged. However, the issue of competing against Rybrevant hasn’t entirely been resolved, with a separate Genmab molecule, MCLA-129, remaining in phase 1/2 development.

The apparent discontinuation of GEN1286 was revealed last week in an update to this project’s study listing on the clinicaltrials.gov registry. Genmab has confirmed to ApexOnco that this premature ending of patient recruitment accurately reflects the project’s status.

Rybrevant and GEN1286 both hit EGFR and cMet, the former as a naked antibody and the latter with an ADC modality. Genmab acquired GEN1286 through its $1.8bn takeover of ProfoundBio.

It was unclear whether Genmab’s separate interest in Rybrevant, a marketed drug that arose from a long-standing discovery alliance with Johnson & Johnson, might have precluded the Danish firm from working on competing projects hitting the same targets, but Genmab clearly decided that it could proceed, starting a phase 1/2 solid tumour study of GEN1286 in November 2024.

Not so fast...

Discontinuation of GEN1286 would have been the end of the matter were it not for the fact that last September Genmab acquired Merus for $8bn. The driver behind this move was petosemtamab, but Merus also brought with it rights to MCLA-129, which happens to be an anti-EGFR x cMet MAb.

MCLA-129 remains in a 576-patient phase 1/2 study in relapsed solid tumours, the most important of which is non-small cell lung cancer. This trial has a primary completion date of March 2026, though it’s still enrolling patients, according to clinicaltrials.gov.

However, MCLA-129 has disappointed clinically, with Merus ruling out development in head and neck cancer back in 2023, and then posting initial NSCLC data showing worrying toxicities, including three deaths due to treatment-related interstitial lung disease. MCLA-129 is also in two trials sponsored by the China licensee Betta, but in the absence of a therapeutic window its future is in doubt.

As for GEN1286, the ProfoundBio-originated project’s sidelining follows recent discontinuations of GEN1160 and GEN1107, and means that the only ProfoundBio asset still in active development is rinatabart sesutecan, an anti-FRα ADC in phase 3 that has been challenged by Lilly’s LY4170156.

What’s left of ProfoundBio?

Source: OncologyPipeline.

This is an updated version of a story published earlier.