Supplemental Material for: Quavonlimab Coformulated With Pembrolizumab Plus Lenvatinib for Advanced Hepatocellular Carcinoma: Nonrandomized Phase 2 KEYSTEP-004 Trial

Adults with confirmed advanced HCC and no prior systemic therapy were enrolled. In the safety lead-in phase, participants received intravenous quavonlimab 25 mg coformulated with pembrolizumab 400 mg every 6 weeks plus oral lenvatinib 12 mg (body weight ≥60 kg) or 8 mg (body weight <60 kg) once daily (dose level 0 [DL0]). Allocation to the efficacy expansion phase was permitted if lenvatinib DL0 plus quavonlimab 25 mg coformulated with pembrolizumab 400 mg every 6 weeks was determined to be tolerable.

Primary end points were objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR) and safety. Secondary end points included duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1 by BICR, and overall survival (OS). Results: As of June 22, 2023, 116 participants were enrolled and 115 were treated.

No dose-limiting toxicities were observed in the safety lead-in phase. Lenvatinib DL0 in combination with quavonlimab 25 mg coformulated with pembrolizumab 400 mg every 6 weeks was determined to be tolerable. Median study follow-up was 18.0 months (range, 12.0-26.6).

Confirmed ORR was 37.4% (95% CI, 28.5-46.9). Median DOR was 10.6 months (range, 1.2+ to 23.1+), median PFS was 8.2 months (95% CI, 6.2-10.2), and median OS was 22.1 months (95% CI, 15.5-not reached). Grade 3-5 treatment-related adverse events (AEs) occurred in 66 participants (57.4%); 14 (12.8%) required high-dose steroids for management of a treatment-related AE.

Conclusion: Quavonlimab coformulated with pembrolizumab plus lenvatinib is an active combination and has a manageable safety profile in advanced HCC.</p>