Abstract 795P
Background
Acral melanoma responds poorly to anti-PD-1 monotherapy. Ori is a HSV-1 derived oncolytic virus expressing granulocyte-macrophage colony-stimulating factor, which has potentiated the efficacy of anti-PD-1 in acral melanoma in the metastatic setting. We conducted a phase Ib trial evaluating ori/tori in resectable stage IIIb-IV (M1a) acral melanoma (NCT04197882).
Methods
Pts received the neoadjuvant intralesional ori up to 8*107pfu/mL*10mL combined with iv tori 3mg/kg every 2 wks*4–6 doses prior to surgery, followed by the adjuvant iv tori 3 mg/kg every 3 wks for 1 year. The primary endpoints included radiological (per RECIST 1.1) and pathological response rates. The secondary endpoints were 1/2-y recurrence-free survival (RFS) and safety.
Results
Thirty patients were enrolled between 07/2019 and 12/2020, with a median age of 57 y.o. (range 21-72), including 14 (47%) males; 12 (40%) with stage IIIB, 14 (47%) with IIIC, and 4 (13%) with IV (M1a) disease. By the last follow-up in 01/2022, all pts have completed the neoadjuvant part, 27 (90%) completed the surgery and tori adjuvant part (the remaining 3 abrogated surgeries due to disease progression). The median follow-up time was 19 months (IQR 15-25). The radiological and pathological (among those who underwent surgeries only) objective response rate was 36.7% (11/30) (95%CI 19.9-56.1) and 77.8% (21/27) (95%CI 57.7-91.4), and that of complete response rate was 3.3% (1/30) (95%CI 0-17.2) and 14.8% (4/27) (95%CI 4.2-33.7), respectively. The 1-y RFS rate was 80.0% (95%CI 66.9-95.7). This combo was well tolerated. Although all pts experienced adverse events (AEs), most were of grade 1/2 (25/30, 83%). Five patients (17%) developed grade 3 AEs, including 2 soft tissue infections, 1 transaminitis, 1 peripheral neuropathy and 1 neutropenia. No grade 4 AE was observed.
Conclusions
Neoadjuvant ori/tori achieved a high pathologic response rate, an impressive 1-y RFS rate, and was well-tolerated in patients with resectable stage IIIB-IV (M1a) acral melanoma. Although longer follow-up is in need, this combo warrants further evaluation in this melanoma subtype.
Clinical trial identification
NCT04197882.
Editorial acknowledgement
Legal entity responsible for the study
Peking University Cancer Hospital and Institute.
Funding
Has not received any funding.
Disclosure
X. Wang: Financial Interests, Personal, Advisory Board: Oriengene. J. Guo: Financial Interests, Personal, Advisory Board: MSD, Roche, Bayer, Novartis, Simcere Pharmaceutical Group, Shanghai Junshi Biosciences, Oriengene; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Leadership Role: CSCO. L. Si: Financial Interests, Personal, Advisory Board: MSD, Roche, Novartis, Shanghai Junshi Biosciences, Oriengene. All other authors have declared no conflicts of interest.