New neoadjuvant combinations in stage III melanoma

The phase 1/2 KEYMAKER-U02 substudy 02C demonstrated promising anti-tumour activity of neoadjuvant pembrolizumab combinations in stage III melanoma, with the highest major pathologic response (pCR) rate observed in the pembrolizumab/favezelimab arm.

In patients with stage III melanoma, PD-1 inhibitors are a standard-of-care for adjuvant treatment and were recently shown to be even more effective in the neoadjuvant setting [1,2]. However, there is still room for further development. Therefore, the phase 1/2 KEYMAKER-U02 substudy 02C (NCT04303169) evaluates the efficacy and safety of neoadjuvant pembrolizumab with or without new agents targeting different immune checkpoint pathways in patients with stage III melanoma.

Dr Alexander Menzies (University of Sydney, Australia) presented the first results of KEYMAKER-U02 substudy [3]. Substudy 02C had 6 treatment arms, with 25 participants enrolled in each. Neoadjuvant therapy was pembrolizumab plus vibostolimab (Arm 1), pembrolizumab plus gebasaxturev (Arm 2), pembrolizumab alone (Arm 3), pembrolizumab plus MK-4830 (Arm 4), pembrolizumab plus favezelimab (Arm 5), and pembrolizumab plus all-trans retinoic acid (Arm 6). After 6 weeks of neoadjuvant treatment participants underwent surgery, followed by adjuvant pembrolizumab. The primary endpoints of KEYMAKER-U02 substudy 02C are safety and pCR.

pCR rates in study arms 1–6 are shown in the Figure. Major pathologic response rates were: 50%, 40%, 47%, 32%, 58%, and 42%, respectively. Event-free survival rates at 18 months in arms 1–4 were 81%, 72%, 80%, 78%, and not yet available for arms 5 and 6. Incidences of grade 3–4 adverse events were 8%, 28%, 7%, 16%, 15%, and 8%, respectively.

Figure: Pathological response in KEYMAKER-U02 substudy 02C [3]



Dr Menzies concluded that “promising anti-tumour activity was observed with all combinations. Numerically, the highest rate of major pathologic response was observed with pembrolizumab/favezelimab. However, direct comparison between arms is restricted because of limited data.”

1. Patel SP, et al. N Engl J Med 2023;388:813-823.
2. Blank CU, et al. N Engl J Med 2024;Jun 2. DOI: 10.1056/NEJMoa2402604.
3. Long GV, et al. KEYMAKER-U02 substudy 02C: Neoadjuvant pembrolizumab (pembro) and investigational agents followed by adjuvant pembro for stage IIIB-D melanoma. Abstract 1082O, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

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Posted on 4 November 20244 November 2024