BNT111 and Cemiplimab Show Promise for Melanoma Patients

New data from the phase 2 BNT111-01 trial indicate that the combination of BNT111 and cemiplimab (Libtayo) may provide a viable treatment option for patients with PD-(L)1-relapsed/refractory melanoma. The trial results, presented at the 2025 ESMO Congress, revealed an objective response rate (ORR) of 18.1% (95% CI, 10.9%-27.4%; P = .0115), allowing researchers to reject the null hypothesis of an ORR below 10%.

The trial included a total of 180 patients, with results showing a complete response (CR) rate of 11.7%, a partial response (PR) rate of 6.4%, and a stable disease (SD) rate of 37.2%. The overall disease control rate (DCR) was recorded at 55.3% (95% CI, 44.7%-65.6%).

Trial Results and Implications

The study’s median follow-up was 15.7 months (range, 0.2-42.2), with a median progression-free survival (PFS) of 3.1 months (95% CI, 1.7-6.9). The 24-month PFS rate stood at 24.9% (95% CI, 14.9%-36.1%). Additionally, the median overall survival (OS) reached 20.7 months (95% CI, 14.4-28.3), with a 24-month OS rate of 47.8% (95% CI, 36.4%-58.4%).

Lead study author Paolo Ascierto, MD, a full professor of oncology at the University of Napoli Federico II and director of the Department of Melanoma, Cancer Immunotherapy and Development Therapeutics at the Istituto Nazionale Tumori IRCCS Fondazione Pascale in Naples, Italy, emphasized the significance of these findings. “The results indicated statistically significant improvement of BNT111 plus cemiplimab compared to an assumed historical control ORR of 10% in heavily pretreated, PD-(L)1-relapsed/refractory advanced or metastatic cutaneous non-acral melanoma,” Ascierto stated.

Study Design and Patient Demographics

The BNT111-01 trial was an open-label, randomized, multi-center, interventional study designed to assess the safety and efficacy of BNT111 combined with cemiplimab as second-line therapy for patients with unresectable stage III or IV melanoma who had previously experienced disease progression on PD-(L)1 therapy.

To qualify for the trial, patients had to present measurable disease, serum lactate dehydrogenase levels below the upper limit of normal, and a history of up to five prior therapies, including ipilimumab (Yervoy). Participants were required to enter the trial within six months of confirmed disease progression and had to have undergone at least 12 weeks of treatment, which included a BRAF-based combination for those with BRAF-mutant disease.

Patients were randomly assigned in a 2:1:1 ratio to receive either BNT111 plus cemiplimab (n = 94; arm 1), BNT111 monotherapy (n = 46; arm 2), or cemiplimab monotherapy (n = 44; arm 3), with treatment lasting up to 24 months. Those in the monotherapy groups were allowed to add the other agent upon confirmation of disease progression, ensuring that all patients had access to the most effective treatment options available.

The primary endpoint of the trial was the ORR evaluated by blinded independent central review per RECIST 1.1 in arm 1, compared against the historical control ORR of 10%. Secondary endpoints included the ORR in monotherapy arms, duration of response, disease control, PFS, OS, and safety metrics.

Baseline characteristics showed that the median age of participants in the combination arm was 64.0 years (range, 18-84), with a majority being male (63.8%) and having an ECOG performance status of 0 (78.7%). Most patients (97.9%) presented with stage IV disease, and a significant proportion had undergone between two and five prior therapies (56.4%).

The safety profile of BNT111, both as a monotherapy and in combination therapy, was considered manageable. Treatment-emergent adverse effects (TEAEs) were reported in 98.9% of cases, with the majority deemed related to BNT111. Notable side effects included pyrexia (76.1%), fatigue (25.0%), and chills (51.1%). Serious TEAEs leading to dose reduction, interruption, or discontinuation were documented in 9.8%, 29.3%, and 6.5% of cases, respectively.

Overall, the findings of the BNT111-01 trial suggest that the combination of BNT111 and cemiplimab may offer a promising new avenue for treatment in patients with difficult-to-treat melanoma, potentially improving outcomes in a patient population that has limited options.