Abstract 1086P
Background
The combination of PD-1 and CTLA-4 blockades showed improved antitumor activities in advanced melanoma. But most data derived from cutaneous subtype and less is known about acral and mucosal patients in East Asia. The study reported updated results of a phase Ia/Ib study that evaluated IBI310 (CTLA-4 inhibitor) alone or plus sintilimab (PD-1 inhibitor) in advanced melanoma including acral and mucosal subjects.
Methods
This was a two-part study. Part A was IBI310 monotherapy setting, and part B was IBI310–sintilimab combination setting. In part A, patients (pts) were treated with IBI310 (IV Q3W) at the doses of 0.3 mg/kg, 1, 2 or 3 mg/kg, for up to 3 cycles (after 28-day DLT evaluation) followed by IBI310 (IV Q12W) if appropriate. In part B, pts with advanced melanoma were treated with IBI310 at the doses of 1, 2 or 3 mg/kg, plus sintilimab at a fixed dose of 200 mg (IV Q3W) for 4 cycles, followed by sintilimab maintenance therapy. The primary endpoint was safety in the two parts and the second endpoints were objective response rate (ORR) and disease control rate (DCR) of the combination therapy.
Results
As of April 14, 2021, 10 and 34 melanoma pts were enrolled in part A and part B, respectively. In part B, there were 3, 31 pts at stage III, IV; 10, 7, 17 pts with 0, 1, ≥2 prior lines of treatments; 24, 9, 1 pts with LDH≤ ULN, > ULN&≤2 x ULN, >2 x ULN respectively. There were no DLTs in the two parts. In part A, only one treatment-related AE (TRAE) of grade 3 (gamma glutamyltransferase increased) was reported; the most commonly reported TRAEs was pruritus (40%). In part B, any grade TRAEs reported in 91.2% of 34 pts, and most were grade 1-2; ≥grade 3 TRAE occurred in 20.6% of 34 pts. No pts experienced Grade 5 TRAE. Among 34 pts in part B, 8 pts obtained complete response (CR) or partial response (PR); the ORR was 23.5% (95% CI: 10.7, 41.2), and DCR was 50.0% (95% CI: 32.4, 67.6). There were 4 SD with decreased target lesions. The ORR were 33.3%, 27.8%, 20.0% for acral, NCSD, and mucosal pts respectively. For pts with 0, ≥1 prior lines of treatments, the ORR were 30% and 20.8% respectively. The part B is ongoing.
Conclusions
IBI310 monotherapy or plus sintilimab were well-tolerated in advanced melanoma. IBI310–sintilimab combination showed a preliminary response benefit in advanced melanoma.
Clinical trial identification
NCT03545971.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Innovent Biologics, Inc.
Disclosure
H. Zhou: Financial Interests, Personal, Full or part-time Employment: Innovent Biologics, Inc.. Y. Wang: Financial Interests, Personal, Full or part-time Employment: Innovent Biologics, Inc.. Q. Hou: Financial Interests, Personal, Full or part-time Employment: Innovent Biologics, Inc.. All other authors have declared no conflicts of interest.