FDA Accepts NDA for Rivoceranib Plus Camrelizumab in Unresectable HCC

• The phase 3 CARES 310 study (NCT03764293) previously evaluated rivoceranib (Apatinib) with camrelizumab (SHR-1210) in patients with unresectable hepatocellular carcinoma (uHCC) and support the FDA acceptance of the new drug application (NDA).
• In the study, the combination demonstrated statistically significant and clinically meaningful prolonged overall survival (OS) and progression-free survival (PFS), and improved overall response rate (ORR) compared with sorafenib (Nexavar).
• The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of May 16, 2024, for the combination.

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The FDA has accepted an NDA for rivoceranib, an oral tyrosine kinase inhibitor (TKI), in combination with camrelizumab, a PD-1 inhibitor, as a first-line treatment option for patients with uHCC.¹

Data from the phase 3 CARES 310 study which evaluated the combination in 543 patients with uHCC support this NDA. In the trial, rivoceranib plus camrelizumab demonstrated a median OS of 22.1 months (95% CI, 19.1-27.2) vs 15.2 mos. (95% CI, 13.0-18.5) for sorafenib, and median PFS rates of 5.6 months (95% CI, 5.5-6.3) vs 3.7 months (95% CI, 2.8-3.7; HR 0.52; 95% CI, 0.41-0.65; P <.0001). Additionally, the confirmed ORR for camrelizumab plus rivoceranib was 25.4% (95% CI, 20.3-31.0) vs 5.9% (95% CI, 3.4-9.4) with sorafenib.

These efficacy results are generally consistent across all subgroups, suggesting that the combination is beneficial in a global uHCC population. Based on these findings, the FDA has assigned a PDUFA target action date of May 16, 2024.

“Rivoceranib plus camrelizumab has demonstrated the potential to improve the lives of those confronted with unresectable hepatocellular carcinoma,” said Saeho Chong, Elevar chief executive officer, in a press release. “With the FDA’s acceptance of our new drug application, we are pleased to reach another milestone in the development of this combination therapy. We look forward to working closely with the FDA during this review process and are focused on making the combination commercially available as quickly as possible should we gain approval.”

The phase 3 CARES trial sought to evaluate the efficacy and safety of camrelizumab with rivoceranib compared with sorafenib as first-line treatment for uHCC.² The international, randomized, open-label, trial enrolled patients with histopathologically or cytologically confirmed advanced HCC who had no previous systematic treatment for HCC, at least 1 measurable lesion, an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, and adequate organ function.

Once enrolled, eligible patients were randomized in a 1:1 fashion to receive camrelizumab 200 mg via intravenous infusion once every 2 weeks plus rivoceranib 250 mg orally every day, or sorafenib 400 mg orally 2 times a day.

The primary end points included PFS per RECIST v1.1 criteria by blinded independent review committee as well as OS. Secondary end points were time to progression, ORR, disease control rate, duration of response, incidence and severity of adverse events, and pharmacokinetics.

Previously in February 2023, the combination of rivoceranib and camrelizumab was approved by the National Medical Products Administration as a first-line treatment for patients with liver cancer in China.1 Rivoceranib monotherapy is also being evaluated and developed as an option for patients with adenoid cystic carcinoma, as well as in combination or alone for other tumor cell types.¹

REFERENCES:

1. Elevar Therapeutics announces FDA acceptance for filing of new drug application for rivoceranib in combination with camrelizumab as a first-line treatment for unresectable hepatocellular carcinoma. News release. Elevar Therapeutics, Inc. July 17, 2023. Accessed July 18, 2023. https://tinyurl.com/h5fy64xt

2. A study to evaluate SHR-1210 in combination with apatinib as first-line therapy in patients with advanced HCC. ClinicalTrials.gov. Updated June 22, 2023. Accessed July 18, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03764293