Abstract CT002: KEYMAKER-U02 substudy 02C: neoadjuvant pembrolizumab (pembro) + vibostolimab (vibo) or gebasaxturev (geba) or pembro alone followed by adjuvant pembro for stage IIIB-D melanoma
Authors: Dummer Reinhard , Robert Caroline , Scolyer Richard A. , Taube Janis M. , Tetzlaff Michael T. , Hill Andrew , Grob Jean-Jacques , Portnoy David C. , Lebbe Celeste , Khattak Muhammad A. , Cohen Jonathan , Bar-Sela Gil , Mehmi Inderjit , Frommer Ronnie Shapira , Meyer Nicolas , Ren Yixin , Fukunaga-Kalabis Mizuho , Krepler Clemens , Long Georgina V. 
Published: April 2023

Abstract
Background: The phase 1/2 KEYMAKER-U02 substudy 02C (NCT04303169) is evaluating neoadjuvant pembro + investigational agents or pembro alone followed by adjuvant pembro in stage IIIB-D melanoma. Results from patients treated with neoadjuvant pembro (anti-PD-1) + vibo (anti-TIGIT; arm 1), pembro + geba (coxsackievirus A21; arm 2), or pembro alone (arm 3) are presented.
Methods: Eligible patients were ≥18 y with resectable stage IIIB, IIIC, or IIID melanoma per AJCC 8th ed criteria, ≥1 measurable lesion per RECIST v1.1, and ECOG PS ≤1. Patients were randomly allocated across open investigational arms. Before resection, patients in arm 1 received 2 administrations of pembro 200 mg Q3W + vibo 200 mg Q3W (cycle 1, day 1; cycle 2, day 1); patients in arm 2 received 1 administration of pembro 400 mg (cycle 1, day 8) + 5 administrations of geba at a fixed dose of 3 × 108 tissue culture infectious dose 50% during cycle 1 (days 1, 3, 5, 8, and 22); and patients in arm 3 received 1 administration of pembro 400 mg. Surgical resection was performed at week 6. At week 12, patients started adjuvant pembro 400 mg Q6W for ≤8 administrations (total treatment duration, ~1 y). Primary end points were safety and tolerability and pCR rate by central review. Secondary end points were near pCR rate and pPR rate by central review and RFS by investigator review. ORR per RECIST v1.1 and EFS by investigator review were exploratory.
Results: At data cutoff (September 9, 2022), 66 patients had been assigned to treatment (arm 1 [pembro + vibo], n = 26; arm 2 [pembro + geba], n = 25; arm 3 [pembro alone], n = 15). Median follow-up was 14.1 mo (range, 8.0-26.1). Treatment-related AEs occurred in 92% of patients in arm 1, 84% in arm 2, and 80% in arm 3. Grade 3/4 treatment-related AEs occurred in 8%, 24%, and 7% of patients, respectively, with no grade 5 treatment-related AEs. 3 patients (12%) in arm 1, 5 (20%) in arm 2, and 0 in arm 3 discontinued any drug because of treatment-related AEs. Immune-mediated AEs or infusion reactions were reported in 31% of patients in arm 1, 32% in arm 2, and 27% in arm 3. The pCR rate was 38% (95% CI, 20-59) in arm 1, 28% (12-49) in arm 2, and 40% (16-68) in arm 3; the near pCR rate was 12% (2-30), 12% (3-31), and 7% (&lt;1-32), respectively; and the pPR rate was 31% (14-52), 12% (3-31), and 27% (8-55), respectively. Median RFS was not reached in any arm; 18-mo RFS rates were 95% (95% CI, 70-99) in arm 1, 87% (56-97) in arm 2, and 73% (24-93) in arm 3. ORR was 50% (95% CI, 30-71), 32% (15-54), and 27% (8-55), respectively. Median EFS was not reached in any arm; 18-mo EFS rates were 81% (95% CI, 60-92), 61% (38-78), and 79% (47-93), respectively.
Conclusions: Neoadjuvant pembro + vibo, pembro + geba, and pembro alone followed by adjuvant pembro had manageable safety and promising antitumor activity in patients with stage IIIB-D melanoma. Of the combination treatments, pembro + vibo showed the most promise.
Citation Format: Reinhard Dummer, Caroline Robert, Richard A. Scolyer, Janis M. Taube, Michael T. Tetzlaff, Andrew Hill, Jean-Jacques Grob, David C. Portnoy, Celeste Lebbe, Muhammad A. Khattak, Jonathan Cohen, Gil Bar-Sela, Inderjit Mehmi, Ronnie Shapira Frommer, Nicolas Meyer, Yixin Ren, Mizuho Fukunaga-Kalabis, Clemens Krepler, Georgina V. Long. KEYMAKER-U02 substudy 02C: neoadjuvant pembrolizumab (pembro) + vibostolimab (vibo) or gebasaxturev (geba) or pembro alone followed by adjuvant pembro for stage IIIB-D melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT002.