Related Experiment Video
Updated: Jun 3, 2025
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D
Reinhard Dummer1, Caroline Robert2, Richard A Scolyer3
1University Hospital Zurich, Zurich, Switzerland. reinhard.dummer@usz.ch.
Abstract:
Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB-D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy. Pathologic complete responses occurred in 10 of 26 patients (38%) with pembrolizumab plus vibostolimab, 7 of 25 (28%) with pembrolizumab plus gebasaxturev and 6 of 15 (40%) with pembrolizumab monotherapy. Major pathologic responses occurred in 13 (50%), 10 (40%) and 7 (47%) patients, respectively. Safety was manageable. Treatment-related adverse events occurred in 24 of 26 patients (92%) with pembrolizumab plus vibostolimab, 21 of 25 (84%) with pembrolizumab plus gebasaxturev and 12 of 15 (80%) with pembrolizumab monotherapy; grade 3 or 4 treatment-related adverse events occurred in 2 (8%), 7 (28%) and 1 (7%) patient in each arm, respectively. No deaths due to adverse events occurred. Exploratory objective responses per RECIST v1.1 were observed in 13 (50%), 8 (32%) and 4 (27%) patients, in each arm, respectively. In a post hoc analysis, scores for tumor mutational burden and an 18-gene T cell-inflamed gene expression profile were generally higher in patients with major pathologic response. Longer follow-up will provide insight into the incremental benefit of combining neoadjuvant pembrolizumab with other therapies in stage IIIB-D melanoma. ClinicalTrials.gov registration: NCT04303169 .
Insights
Neoadjuvant pembrolizumab combined with other therapies shows promise for melanoma treatment. Pembrolizumab plus vibostolimab demonstrated high pathologic complete response rates in stage IIIB-D melanoma patients.
Area of Science:
- Oncology
- Immunotherapy
- Melanoma Research
Background:
- Neoadjuvant immunotherapies are being investigated for their antitumor effects in melanoma.
- The KEYMAKER-U02 trial is assessing neoadjuvant pembrolizumab (anti-PD-1) in various combinations for stage IIIB-D melanoma.
Purpose of the Study:
- To report findings from the first three arms of the KEYMAKER-U02 substudy 02C.
- To evaluate neoadjuvant pembrolizumab monotherapy, pembrolizumab plus vibostolimab (anti-TIGIT), and pembrolizumab plus gebasaxturev (coxsackievirus A21).
Main Methods:
- Phase 1/2, adaptive-design clinical trial (KEYMAKER-U02, Substudy 02C).
- Patients with stage IIIB-D melanoma received neoadjuvant pembrolizumab alone or in combination, followed by adjuvant pembrolizumab.
- Assessed pathologic complete response, major pathologic response, safety, and objective response rates per RECIST v1.1.
Main Results:
- Pathologic complete responses: 40% (pembrolizumab), 38% (pembrolizumab + vibostolimab), 28% (pembrolizumab + gebasaxturev).
- Major pathologic responses observed in 47%, 50%, and 40% of patients, respectively.
- Safety was manageable, with most treatment-related adverse events being low grade; no deaths occurred due to adverse events.
Conclusions:
- Neoadjuvant pembrolizumab-based regimens show antitumor activity in stage IIIB-D melanoma.
- Higher tumor mutational burden and T cell-inflamed gene expression profiles correlated with major pathologic response.
- Further follow-up is needed to determine the incremental benefit of combination therapies.
