Bicara chases Merus

The battle of souped-up EGFR-targeting biologicals has moved up a gear, with the private US biotech Bicara Therapeutics yesterday challenging Merus with results in first-line head and neck cancer that it claims could change the treatment of this disease.

The data revealed a median progression-free survival for Bicara’s project, the anti-EGFR x TGF-β fusion protein ficerafusp alfa, that for the first time hit a range analysts had earlier suggested would be clinically meaningful. In the same setting Merus’s anti-EGFR x LGF5 MAb petosemtamab had data at ASCO that appeared comparable on ORR, but which weren’t sufficiently mature to show PFS.

Bicara’s ficerafusp, formerly known under the lab code BCA101, is seen as a threat to petosemtamab, and Bicara has been turning up the volume since raising $108m in March 2023. Ficerafusp and petosemtamab are both being combined with Keytruda, specifically in PD-L1-expressing first-line head and neck cancer, so far in uncontrolled trials.

9.8-month median

The Bicara project impressed at ASCO 2023, with headline numbers including an ORR of 48% among 31 patients, a result driven by a 65% response rate among those whose cancer had no HPV involvement – an especially tough group.

Yesterday Bicara said ORR was now 54% in 39 evaluable patients, and 64% in those with HPV-negative disease. More importantly, it cited updated mPFS of 9.8 months in HPV-negative patients, having earlier given a number of 6.6 months for all-comers. Analysts covering Merus earlier said 8 months’ mPFS would be a number suggestive of clinical relevance.

For its part Merus hasn’t yet revealed survival from its peto/Keytruda combo trial, and the first PFS data aren’t expected until next year. On ORR peto looks comparable, at 62% among 26 patients reported at ASCO this month. Merus has also claimed that this activity is maintained irrespective of HPV involvement.

This point is important since Bicara appears to have given up on the HPV-positive subgroup. When the company completed a $165m series C fund raising in December it said proceeds would fund the development of ficerafusp specifically in HPV-negative first-line head and neck cancer.

This is understandable, given that ficerafusp response rates in HPV-positive patients don’t appear to be meaningfully higher than those for Keytruda alone. As such Merus could have the edge here, though it must be stressed that petosemtamab data in HPV-positives so far amount to just four evaluable subjects.

Cross-trial comparison in PD-L1-positive 1st-line head & neck cancer

Notes: *3 of these responses failed to be confirmed; **anecdotal numbers, as these data haven’t formally been split out. Surce: ASCO & OncologyPipeline.

A further point of differentiation between Merus and Bicara is safety. So far ficerafusp has yielded a relatively high rate of adverse event-related treatment discontinuations – 14% – versus 4% in the petosemtamab trial. All grade 3 or higher treatment-related adverse event rates stand at 40% for ficerafusp, and 24% for petosemtamab.

The idea behind ficerafusp is to combine the anti-EGFR mechanism of Erbitux with TGF-β trapping to prevent resistance; petosemtamab, meanwhile, combines anti-EGFR activity with inhibition of LGR5, a protein thought to cause EGFR internalisation and degradation. The merits of each approach will continue to be debated.

The first PFS data for petosemtamab, and revelation of Merus and Bicara's pivotal study plans, are eagerly awaited.