FDA Holds Pre-NDA Meeting to Discuss Rivoceranib Plus Camrelizumab for HCC

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Representatives from Elevar Therapeutics and the FDA held a positive pre–new drug application meeting to discuss the combination of rivoceranib and camrelizumab as a potential therapeutic option for patients with hepatocellular carcinoma.

Representatives from Elevar Therapeutics and the FDA held a positive pre–new drug application (NDA) meeting to discuss the combination of rivoceranib and camrelizumab as a potential therapeutic option for patients with hepatocellular carcinoma (HCC).¹

Elevar plans to file an NDA for the combination as early as feasible in 2023, according to a press release. Additionally, Elevar aims to file an NDA for rivoceranib monotherapy as a potential treatment option for adenoid cystic carcinoma (ACC) by the end of 2022.

“Our team at Elevar is very pleased with the results of our pre-NDA meeting with respect to rivoceranib plus camrelizumab as a treatment option for HCC, continuing a collaborative process with the FDA that allows us to maintain our timeline for the upcoming rivoceranib FDA filings in two indications with clearly demonstrated unmet medical need,” Saeho Chong, chief executive officer of Elevar, stated in a press release.

“As evidenced by data shared this year, rivoceranib is proving to be efficacious in both monotherapy for ACC and in combination with an anti-PD1 inhibitor, for HCC, and we are excited to continue its regulatory development in the months ahead.”

Data from a phase 3 trial (NCT03764293) presented at the 2022 ESMO Congress showed that rivoceranib/camrelizumab elicited survival benefits vs sorafenib in patients with unresectable HCC.²

Findings showed that patients treated with rivoceranib/camrelizumab achieved a median overall survival (OS) of 22.1 months (95% CI, 19.1-27.2) compared with 15.2 months (95% CI, 13.0-18.5) for those treated with sorafenib (HR, 0.62; 95% CI, 0.49-0.80; P <.0001). Additionally, the combination elicited a median progression-free survival (PFS) of 5.6 months (95% CI, 5.5-6.3) vs 3.7 months (95% CI, 2.8-3.7) for sorafenib (HR, 0.52; 95% CI, 0.41-0.65; P <.0001).

The randomized, open-label, international, multicenter, phase 3 trial examined the efficacy and safety of the combination of rivoceranib plus camrelizumab vs sorafenib in previously untreated patients with unresectable or metastatic HCC of Barcelona Clinic Liver Cancer stage B or C. Patients were also required to have an ECOG performance status of 0 or 1, be Child-Pugh grade A, and have at least 1 measurable lesion per RECIST v1.1 criteria.

Enrolled patients were randomly assigned to receive 200 mg of intravenous camrelizumab every 2 weeks plus 250 mg of daily oral rivoceranib or 400 mg of oral sorafenib twice daily. Treatment continued until the loss of clinical benefit or unacceptable toxicity.

The co-primary end points consisted of PFS and OS. Overall response rate (ORR) served as a secondary end point.

Additional data presented at the 2022 ESMO Congress showed that the 12- and 18-month OS rates in the rivoceranib plus camrelizumab arm were 76.5% and 60.9%, respectively, compared with 60.8% and 45.2% in the sorafenib arm. Furthermore, the 6-month PFS rates in the experimental and control arms were 44.6% and 22.7%, respectively.

Patients treated with rivoceranib plus camrelizumab experienced a confirmed ORR of 25.4% (95% CI, 20.3%-31.0%) compared with 5.9% (95% CI, 3.4%-9.4%) for those who received sorafenib, per RECIST v1.1 criteria (P <.0001). Per modified RECIST v1.1 criteria, the ORRs in the experimental and control arms were 33.1% (95% CI, 27.5%-39.0%) and 10% (95% CI, 6.7%-14.2%), respectively (P <.0001).

Regarding safety, 80.5% of patients experienced grade 3/4 treatment-related adverse effects (TRAEs) in the camrelizumab/rivoceranib arm vs 52% in the sorafenib group. One grade 5 TRAE occurred each group. Additionally, 24.3% of patients treated with the combination experienced serious TRAEs vs 5.9% in the single agent arm.

In the combination arm, 80.5% of patients required dose modifications or interruptions due to TRAEs compared with 50.2% in the sorafenib arm. In the combination arm, 3.7% of patients required treatment discontinuation of all treatment components vs 4.5% for sorafenib.

References

Elevar Therapeutics announces positive pre-NDA meeting for rivoceranib combination with camrelizumab as hepatocellular carcinoma treatment option. News release. Elevar Therapeutics. October 11, 2022. Accessed October 12, 2022. https://bit.ly/3Te1Lsh
Qin S, Chan LS, Gu S, et al. Camrelizumab (C) plus rivoceranib (R) vs. sorafenib (S) as first-line therapy for unresectable hepatocellular carcinoma (uHCC): A randomized, phase III trial. Ann Oncol. 2022;33(suppl 7):S1401-S1402. doi:10.1016/j.annonc.2022.08.032