Abstract 981P
Background
CS1002 is a humanized immunoglobulin G1 (IgG1) mAb directed against CTLA-4, and CS1003 is a humanized, recombinant IgG4 anti-PD-1 mAb. In dose-escalation phase Ia, CS1002 was well-tolerated with no dose-limiting toxicities (DLTs) in patients (pts) with solid tumors. Phase Ib includes dose-escalation (part 2) and dose-expansion (part 3) to assess the safety and antitumor activity of C1002 combined with CS1003 in selected tumors. Part 2 showed the combination was well-tolerated with no DLT and a maximum toxicity dose was not reached. Here we present the safety and efficacy of CS1002 and CS1003 in part 3.
Methods
In part 3, pts with anti-PD-(L)1 naïve pretreated MSI-H/dMMR tumors or anti-PD-(L)1 refractory melanoma were randomized and treated with CS1002 (Arm A: CS1002 0.3 mg/kg, once every six weeks (Q6W), continuous; Arm B: CS1002 1 mg/kg Q3W, up to 4 doses) and CS1003 200 mg fixed dose Q3W continuously. Safety and antitumor activity were assessed.
Results
As of 01 March 2021, 33 pts with MSI-H/dMMR tumors or melanoma (16 in A and 17 in B) were enrolled and treated with CS1002 and CS1003. Twenty-nine (87.9%) pts experienced adverse events (AEs) (A: 81.3%; B: 94.1%), of whom 21 (63.6%) pts had treatment-related AEs (TRAEs) (A: 62.5%; B: 64.7%). The most common TRAEs (≥20%) were diarrhoea and fatigue (7 pts each, 21.2%). CTCAE Grade ≥3 CS1002 and CS1003-related AEs occurred in 5 (15.2%) pts (2 in A and 3 in B). Serious AEs related to treatment were reported in 6 (18.2%) pts (3 each in A and B). Two (6.1%) pts experienced AEs leading to discontinuation of CS1002 and CS1003. No death due to AEs was reported. Of 9 and 7 evaluable pts with MSI-H/dMMR tumors in A and B, objective response rate (ORR) was 44.4% (4 pts had partial response, PR) and 57.1% (1 had complete response and 3 had PR), respectively. Among 4 evaluable pts with melanoma each in A and B, ORR was both 50% with 2 pts each achieving PR.
Conclusions
The combination of CS1002 and CS1003 demonstrated an acceptable safety profile and showed promising preliminary anti-tumor activity in pts with MSI-H/dMMR tumors and anti-PD-(L)1 refractory melanoma at two dose levels. One dose regimen will be chosen to support further exploration.
Clinical trial identification
NCT03523819.
Editorial acknowledgement
We acknowledged Xin Zhai (CStone Pharmaceuticals, Suzhou, China) provided medical writing support under the direction of the authors.
Legal entity responsible for the study
CStone Pharmaceuticals (Su Zhou) Co. Ltd.
Funding
CStone Pharmaceuticals (Su Zhou) Co. Ltd.
Disclosure
S. Bishnoi: Financial Interests, Personal, Stocks/Shares: Telix; Financial Interests, Personal, Stocks/Shares: Regeneron. M. Moore: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Merck. R. Eek: Financial Interests, Personal, Ownership Interest: Novartis; Financial Interests, Personal, Ownership Interest: Gilead. R. Zielinski: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Tilray; Financial Interests, Personal, Advisory Board: Pfizer; Non-Financial Interests, Personal, Leadership Role: COSA Rural and Regional Oncology work group. L.S. Chan: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Principal Investigator: Eisai; Financial Interests, Personal, Principal Investigator: MSD; Financial Interests, Personal, Principal Investigator: Ipsen; Financial Interests, Institutional, Sponsor/Funding: Eisai; Financial Interests, Institutional, Sponsor/Funding: MSD; Financial Interests, Institutional, Sponsor/Funding: Ipsen. A.N. Tse: Financial Interests, Personal, Ownership Interest: CStone; Financial Interests, Personal, Officer: CStone. All other authors have declared no conflicts of interest.