AACR 2025 – BioNTech sees its first combo glimmers

BioNTech has been ramping up combination efforts with its PD-L1 x VEGF bispecific antibody BNT327 and various ADCs, and at AACR the first data emerged to back this approach. The results are encouraging but early, involving just 13 platinum-resistant ovarian cancer patients in a phase 1/2 trial in various solid tumours testing BNT327 plus the TROP2-targeting ADC BNT325.

There were seven partial responses, giving an ORR of 54%, which looks in line with the 56% ORR recently reported with Genmab’s folate receptor alpha-targeting ADC rinatabart sesutecan in late-line ovarian, with the usual caveats about cross-trial comparisons.

The BNT327 plus BNT325 study, which is global but sponsored by the latter’s originator DualityBio, has also enrolled patients with NSCLC, TNBC and cervical cancer, but efficacy data on these cohorts weren’t given, with the presenter, Dr Erika Hamilton of the Sarah Cannon Research Institute, noting that the ovarian arm had the most patients with the highest data maturity, as it was the first to start enrolling.

She described adverse events with the combo as manageable, highlighting a 5% discontinuation rate in the 67-patient-strong safety analysis. However, one fatal pneumonia case was deemed possibly related to therapy.

BioNTech has long said that it hopes to replace chemo with ADCs as the combo partner of choice, and has other trials under way or planned with various ADCs licensed from the likes of DualityBio and MediLink.

The rationale behind such combinations, according to Hamilton, is that ADCs could stimulate tumour immunity and increase the sensitivity of tumours to PD-L1 inhibition. Potential mechanisms for increased efficacy of BNT327 with ADCs include induction of immunogenic cell death, maturation of dendritic cells, increase in T-cell infiltration, improved immunological memory and expression of immune regulatory proteins; she added that the anti-angiogenic function of BNT327, via its VEGF-targeting arm, could facilitate ADC penetration.

BNT327 + ADCs: ongoing & planned combo trials

Note: HCC=hepatocellular carcinoma; HNSCC=head & neck squamous cell carcinoma; NSCLC=non-small cell lung cancer; PROC=platinum-resistant ovarian cancer; SCLC=small-cell lung cancer; TNBC=triple-negative breast cancer. Source: OncologyPipeline & company releases.