985P - Analysis of antidrug antibodies (ADA) to camrelizumab in CARES-310: The pivotal phase III study of camrelizumab + rivoceranib in unresectable hepatocellular carcinoma (uHCC)

Background

High ADA levels can reduce systemic drug exposure of biologic therapies, and ADAs that are neutralizing (NAb) can attenuate pharmacodynamic effects. CARES-310 evaluated the combination of an anti-PD-1 antibody, camrelizumab (cam), and a VEGFR-2 inhibitor, rivoceranib (rivo) (n=272), compared to sorafenib (sor) (n=269) for the treatment of uHCC. Cam + rivo significantly improved OS and PFS compared to sor. The most common (≥20%) grade ≥3 treatment-related adverse events in the cam + rivo arm were hypertension (37.5%) and increased AST (16.5%) vs palmar-plantar erythrodysesthesia (15.2%) in the sor arm. The CARES-310 study evaluated ADA and NAb to cam.

Methods

Electrochemiluminescent immunoassays were used to detect ADAs and NAbs to cam in serum samples at sensitivities of 1.7-10.9 ng/mL and 210 ng/mL, respectively. Pharmacokinetics was assessed in ADA+ (n=54) and ADA- (n=199) patients, with positive patients stratified by median titers. Efficacy and safety were assessed by ADA+ and ADA- status.

Results

ADA and NAb incidences were 21.3% (n=54) and 21.7% (n=55), respectively. Among ADA +, ADAs in 38 patients were persistent, and ADAs in 19 patients were pre-existing. Median ADA onset and duration were 8.1 and 5.1 weeks, respectively. Steady-state clearance (L/day) in the < median titer group (mean, 0.25) and the ≥ median titer group (mean 0.29) were numerically higher than the ADA- group (mean 0.20), but ranges overlapped. Demographic imbalance was observed between ADA+ and ADA- subgroups. There were no clinically significant impacts of ADA status on efficacy or safety (Table).

Table: 985P

ADA, antidrug antibodies; PFS, progression-free survival; OS, overall survival; NR, not reached; AE, adverse event.

Conclusions

There was minimal impact of ADAs on PK, efficacy, and safety. Therefore, follow-up monitoring of ADAs to cam is not warranted.

Clinical trial identification

NCT03764293.

Editorial acknowledgement

Legal entity responsible for the study

Elevar Therapeutics; Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Elevar Therapeutics; Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

A.O. Kaseb: Financial Interests, Personal, Research Grant: BMS, Roche, Genentech, Merck, Eisai, Exelixis, Hengrui, Adaptimmune, Tvardi; Financial Interests, Personal, Other, Consulting Fees: BMS, Roche, Genentech, Merck, Eisai, Exelixis, Elevar Therapeutics; Financial Interests, Personal, Speaker’s Bureau: BMS, Roche, Genentech, Merck, Eisai, Exelixis, Elevar Therapeutics. J. Bugni, M. Karkhanis, X. Meng, S.H. Jang, K. Ryan, L. Alexander: Financial Interests, Personal, Full or part-time Employment: Elevar Therapeutics; Financial Interests, Personal, Stocks/Shares: Elevar Therapeutics. M. Zhou, K. Shen, C. Yang, M. Yu: Financial Interests, Personal, Full or part-time Employment: Hengrui USA. All other authors have declared no conflicts of interest.