FDA Approval Sought for Frontline Camrelizumab Plus Rivoceranib in uHCC

A new drug application (NDA) has been submitted to the FDA, seeking approval of rivoceranib in combination with camrelizumab (SHR-1210) for the frontline treatment of patients with unresectable hepatocellular carcinoma (uHCC).¹

Findings from the phase 3 CARES 310 study (NCT03764293) support the NDA. Topline data from the study showed that camrelizumab plus rivoceranib met its primary end point by demonstrating overall survival (OS) and progression-free survival (PFS) improvements vs sorafenib (Nexavar).^1,2

A total of 543 patients with uHCC made up the intent-to-treat population of the randomized, open-label, international, multicenter CARES 310 study. Patients in the experimental arm were given camrelizumab 200 mg intravenously (IV) in combination with rivoceranib in a 250 mg tablet. In the control arm, patients received oral sorafenib in a 0.2 g tablet.²

In addition to survival, the study investigated time to response, objective response rate (ORR), disease control rate (DCR), duration of response, the incidence and severity of adverse events, serum concentration of camrelizumab and plasma concentration rivoceranib, and the number of anti-camrelizumab antibody and neutralizing antibody from baseline as secondary end points.,

In 543 patients with uHCC who made up the intent-to-treat population of the study, the median OS was 22.1 months (95% CI 19.1-27.2 months) with rivoceranib in combination with camrelizumab vs 15.2 months (95% CI, 13.0-18.5 months) with sorafenib (HR, 0.62; 95% CI, 0.49-0.80; 1-sided P < .0001). Camrelizumab plus rivoceranib also achieved a median PFS of 5.6 months (95% CI, 5.5-6.3) vs 3.7 months (95% CI, 2.8-3.7) with sorafenib (HR, 0.52; 95% CI, 0.41-0.65; 1-sided P < .0001).

The 6-month PFS rate with camrelizumab plus rivoceranib was 44.6% vs 22.7% with sorafenib. Regarding OS, the 12-month OS rate was 76.5% in the camrelizumab plus rivoceranib arm compared with 60.8% in the sorafenib arm. The 18-month OS rate was 60.9% with camrelizumab plus rivoceranib compared with 45.2% in the sorafenib arm.

Notably, the survival benefits associated with the experimental combination were carried into select subgroups.

Results from the secondary end points showed that the confirmed objective response rate (ORR) by blinded independent review committee and RECIST v1.1 criteria was 25.4% with camrelizumab plus rivoceranib vs 5.9% with sorafenib (P < .0001). The ORR was comprised of 3 complete responses (CR) in the camrelizumab plus rivoceranib arm vs 1 CR in a patient treated with sorafenib. Per modified RECIST criteria, there were 14 CRs in the experimental arm vs 3 in the control arm, for a DCR of 78.3% vs 53.9%, respectively, per RECIST v1.1. The DCR was inclusive of stable disease rates and rates were similar when observed by modified RECIST criteria.

For safety, grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 80.5% of patients in the camrelizumab plus rivoceranib arm vs 52% in the sorafenib group. Only 1 grade 5 event occurred during the study in a patient treated with sorafenib. Serious TRAEs occurred 24.3% of the experimental arm compared with 5.9% of the control arm.

Dose modifications or interruptions resulting from TRAEs were required for 80.5% of patients in experimental arm vs 50.2% in the control arm.

The most common grade ≥ 3 TRAEs observed with rivoceranib in combination with camrelizumab were hypertension (37.5%), aspartate aminotransferase increase (16.5%), alanine aminotransferase increase (12.9%), palmar-plantar erythrodysesthesia (PPE; 12.1%), and platelet count decrease (11.8%). In the sorafenib arm, the most common grade ≥ 3 TRAEs included PPE (15.2%) and hypertension (14.9%).

_REFERENCES:

_{1. Elevar Therapeutics submits new drug application to FDA for combination of rivoceranib and camrelizumab as first-line treatment option for unresectable hepatocellular carcinoma. News release. Elevar Therapeutics, Inc. May 17, 2023. Accessed May 18, 2023. https://bit.ly/42Vg5eQ}

_{2. Elevar Therapeutics announces camrelizumab plus rivoceranib significantly prolonged overall survival and progression-free survival versus sorafenib in patients with unresectable hepatocellular carcinoma during phase 3 trial, a joint program with Hengrui Pharma. News release. Elevar Therapeutics, Inc. September 7, 2022. Accessed May 18, 2023. https://bit.ly/3OjiIm9}