BNT111 and Cemiplimab Show Promising Results in Melanoma Trial

A recent phase 2 clinical trial has revealed that the combination of BNT111 and cemiplimab (Libtayo) demonstrated a notable objective response rate (ORR) of 18.1% in patients suffering from PD-(L)1-relapsed or refractory melanoma. This significant outcome allows researchers to reject the null hypothesis of an ORR below 10%, according to findings presented at the 2025 ESMO Congress.

The trial, known as BNT111-01, involved 180 participants with advanced melanoma who had previously undergone treatment with PD-(L)1 therapies. Among the results, investigators noted 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 reported at 55.3%.

With a median follow-up of 15.7 months, the median progression-free survival (PFS) was found to be 3.1 months, while the 24-month PFS rate stood at 24.9%. The median overall survival (OS) reached 20.7 months, with a 24-month OS rate of 47.8%.

Dr. Paolo Ascierto, a leading expert in oncology at the Istituto Nazionale Tumori IRCCS Fondazione Pascale in Naples, Italy, emphasized the importance of these results, stating, “The results indicated statistically significant improvement of BNT111 plus cemiplimab vs an assumed historical control ORR of 10% in heavily pretreated, PD-(L)1-relapsed/refractory advanced or metastatic cutaneous non-acral melanoma.”

The encouraging topline results were initially disclosed in July 2024, following the FDA granting fast track designation to BNT111 for patients with advanced melanoma. This investigational treatment is an uridine RNA-based lipoplex cancer immunotherapy targeting nonmutated, tumor-associated antigens such as NY-ESO-1, MAGE-A3, Tyrosinase, and TPTE.

The BNT111-01 trial was designed as an open-label, randomized, multi-center study aimed at assessing the safety and efficacy of the BNT111 and cemiplimab combination as a second-line therapy for patients with unresectable stage III or IV melanoma. Eligibility criteria required participants to have measurable disease, serum lactate dehydrogenase levels within normal limits, and a history of up to five prior treatment lines, including ipilimumab (Yervoy).

Patients were required to enter the trial within six months of confirmed disease progression and must have received at least 12 weeks of treatment that included a BRAF-based combination for those with BRAF-mutant disease. Of the 180 patients enrolled, participants were randomized in a 2:1:1 ratio to receive either BNT111 plus cemiplimab (n = 94), BNT111 monotherapy (n = 46), or cemiplimab monotherapy (n = 44), with treatments lasting up to 24 months.

Patients in the monotherapy groups were permitted to initiate the other agent upon confirming disease progression. The primary endpoint of the trial was the ORR, evaluated by blinded independent central review according to RECIST 1.1, compared against an assumed historical control ORR of 10%. Secondary endpoints encompassed overall response rates in the monotherapy arms, duration of response, DCR, time to response, PFS, OS, safety, tolerability, and patient-reported outcomes.

Baseline characteristics of the combination therapy group revealed a median age of 64.0 years, with 63.8% of patients being male and 78.7% exhibiting an ECOG performance status of 0. Most participants had stage IV disease at baseline (97.9%), with 44.7% presenting M1c disease and an average of 2 to 5 prior therapies (56.4%). A significant portion of patients were classified as PD-(L)1 refractory (56.4%) and had liver metastases (25.5%).