Neoadjuvant vibostolimab plus pembrolizumab has shown antitumor activity in patients with stage IIIB-D melanoma, according to research presented at the AACR Annual Meeting 2023.
In a phase 1/2 study, vibostolimab plus pembrolizumab appeared to be more effective than gebasaxturev plus pembrolizumab or pembrolizumab alone.
Patients who received vibostolimab plus pembrolizumab had numerically higher objective response, event-free survival (EFS), and recurrence-free survival (RFS) rates.
The study (ClinicalTrials.gov Identifier: NCT04303169) included 66 patients with resectable stage IIIB-D melanoma. Prior to resection, patients were randomly assigned to receive:
- The anti-TIGIT antibody vibostolimab and pembrolizumab, both at 200 mg on day 1 and 21 of a single cycle (n=26)
- Five injections of the oncolytic virus gebasaxturev plus pembrolizumab at 400 mg on day 1 of the cycle (n=25)
- Pembrolizumab monotherapy at 400 mg on day 1 of the cycle (n=15).
After surgery, all patients received pembrolizumab at 400 mg every 6 weeks for up to 8 cycles. Baseline characteristics were generally well balanced across the treatment arms. The median follow-up was 14.1 months.
The objective response rate was 50% in the vibostolimab arm, 32% in the gebasaxturev arm, and 27% in the pembrolizumab monotherapy arm. In the vibostolimab arm, 2 patients had a complete response. There were no complete responses with the other therapies.
The pathologic complete response rate was 38% in the vibostolimab arm, 28% in the gebasaxturev arm, and 40% in the monotherapy arm.
The 18-month EFS rate was 85% in the vibostolimab arm, 70% in the gebasaxturev arm, and 78% in the pembrolizumab monotherapy arm. The median EFS was not reached in any arm.
Similarly, the median RFS was not reached in any arm. The 18-month RFS rate was 95% in the vibostolimab arm, 87% in the gebasaxturev arm, and 73% with pembrolizumab alone.
Grade 3-4 treatment-related adverse events (TRAEs) occurred in 8% of patients in the vibostolimab arm, 24% in the gebasaxturev arm, and 7% in the monotherapy arm. The most common TRAE of any grade was pruritus (46%, 36%, and 33%, respectively).
Early treatment discontinuation due to TRAEs occurred in 12% of patients in the vibostolimab arm, 20% in the gebasaxturev arm, and none of the patients in the pembrolizumab monotherapy arm.
These results support further investigation of vibostolimab plus pembrolizumab in the adjuvant and neoadjuvant settings, said study presenter Reinhard Dummer, MD, of the University Hospital Zurich in Switzerland.
Researchers are currently testing the combination in the adjuvant setting in the phase 3 KEYVIBE-010 trial (ClinicalTrials.gov Identifier: NCT05665595).
Disclosures: This research was supported by Merck Sharp & Dohme, LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Dummer R, Robert C, Scolyer RA, et al. KEYMAKER-U02 substudy 02C: Neoadjuvant pembrolizumab (pembro) + vibostolimab (vibo) or gebasaxturev (geba) or pembro alone followed by adjuvant pembro for stage IIIB-D melanoma. AACR 2023. April 14-19, 2023. Abstract CT002.