A closer look at phase 3 data on BioNTech and OncoC4’s anti-CTLA-4 antibody has shown the efficacy that excited analysts last week is offset by a challenging tolerability profile.
Analysts got an early look at data on gotistobart in an abstract published ahead of a presentation at the IASLC ASCO 2025 North America Conference on Lung Cancer over the weekend. After seeing the abstract, BMO Capital Markets analysts said in a note to investors that the efficacy results are strong, but the lack of comprehensive data on immune-related toxicities left a key tolerability question unanswered.
The presentation suggests tolerability is an issue. TD Cowen analysts said in a note to investors that 60% of patients on the CTLA-4 prospect, called gotistobart, had immune-related adverse events. The rate of treatment-related adverse events leading to treatment discontinuation was 13% for gotistobart and 5% for the control.
Tolerability, specifically immune-related adverse events, is a known concern with CTLA-4 blockers. Bristol Myers Squibb created the space with Yervoy, but immune-mediated toxicities give the antibody a narrow therapeutic window.
OncoC4, which licensed gotistobart to BioNTech for $200 million upfront in 2023, tried to create a safer, more tolerable anti-CTLA-4 antibody through features such as its pH-dependent mechanism. While the phase 3 data suggest tolerability remains a concern, TD Cowen analysts concluded the overall profile is encouraging given the unmet need in the targeted non-small cell lung cancer (NSCLC) population.
“The current data suggests gotistobart offers solid efficacy and is underappreciated with potential to be a viable option in [second-line squamous] NSCLC,” the analysts said. “This could be a nice commercial opportunity for the company as it continues to advance to launching their own oncology pipeline.”
BioNTech and OncoC4 reported a 12-month overall survival (OS) rate of 63.1% for gotistobart compared to 30.3% for docetaxel. At a median follow-up of 14.5 months, the gotistobart arm hadn’t reached the median OS. Median OS in the docetaxel arm was 10 months.
BMO analysts said in a note that the “clear separation in OS curves is highly encouraging when assessing gotistobart's efficacy.”
The data come from 87 people with metastatic squamous NSCLC who received gotistobart or docetaxel as a second or later line of systemic therapy. OncoC4 and BioNTech enrolled the patients in the non-pivotal part of a phase 3 trial. The pivotal stage of the study, which is designed to enroll about 500 patients, is ongoing and has a primary completion date in June 2026, according to ClinicalTrials.gov.
Phase 2 trials are testing gotistobart in combination with Merck & Co.’s Keytruda in platinum-resistant ovarian cancer and with Novartis’ Pluvicto in metastatic castration-resistant prostate cancer. TD Cowen analysts said the markets targeted by the phase 2 trials are more competitive than the lead indication.