FDA Clears Manufacturing Concern Behind Rivoceranib/Camrelizumab CRL in HCC

HLB and its US subsidiary, Elevar Therapeutics, have received a voluntary action indicated (VAI) close-out letter from the FDA regarding the current good manufacturing practice (cGMP) inspection that led to the agency’s most recent complete response letter (CRL) for rivoceranib plus camrelizumab as a first-line treatment for unresectable or metastatic hepatocellular carcinoma (HCC), according to a report from The Korea Herald citing statements from HLB.¹ The developer stated that a VAI classification will not directly and negatively affect the FDA’s assessment of pending marketing applications that reference the inspected facility.

What did the FDA’s inspection find?

The close-out letter followed an on-site cGMP inspection of the Chinese manufacturing facility operated by Jiangsu Hengrui Pharmaceuticals, where rivoceranib is currently produced. A VAI classification indicates that inspectors identified minor issues or objectionable conditions that do not require formal enforcement or legal action; it sits between the best possible outcome, no action indicated (NAI), and the most serious outcome, official action indicated (OAI).

According to HLB, the FDA’s letter stated that a VAI classification for cGMP compliance would not directly and negatively affect the agency’s assessment of pending marketing applications referencing the facility.

How does this affect the path forward for rivoceranib/camrelizumab?

The developers reported that they believed the “key issues” troubling the new drug application (NDA) were mostly resolved, and that they intended to resume the rivoceranib/camrelizumab NDA process by working with the FDA.¹

What is the regulatory history behind this CRL?

This VAI indication from the FDA came after rivoceranib plus camrelizumab received its third CRL for the first-line treatment of unresectable or metastatic HCC, which the FDA issued on July 10, 2026.² The CRL was brought on after deficiencies were identified during a routine cGMP inspection of the rivoceranib manufacturing site.

The FDA first rejected the NDA in May 2024 over concerns related to the camrelizumab manufacturing facility, then issued a second CRL in March 2025 without specifying a reason.^3,4 Developers resubmitted the NDA in January 2026, and the FDA accepted the resubmission that same month, assigning a PDUFA target action date of July 23, 2026 before issuing the third CRL ahead of that date.⁵

What is the efficacy and safety of rivoceranib plus camrelizumab in this indication?

The NDA was supported by data from the phase 3 CARES-310 trial (NCT03764293), in which camrelizumab plus rivoceranib were evaluated vs sorafenib (Nexavar) monotherapy in patients with previously untreated unresectable HCC.

As of the final analysis on June 14, 2023, with a median follow-up of 22.1 months (IQR, 11.9-30.3), the combination showed a median overall survival of 23.8 months (95% CI, 20.6-27.2) vs 15.2 months (95% CI, 13.2-18.5) with sorafenib (HR, 0.64; 95% CI, 0.52-0.79; P <.0001), and a median progression-free survival of 5.6 months (95% CI, 5.5-7.4) vs 3.7 months (95% CI, 3.1-3.7), respectively (HR, 0.54; 95% CI, 0.44-0.67; P <.0001).⁵

Grade 3 or 4 treatment-related adverse events were noted in both groups, with the most common being hypertension (39% in the investigational arm vs 15% in the sorafenib arm), palmar-plantar erythrodysesthesia syndrome (12% vs 16%), increased aspartate aminotransferase (17% vs 5%), and increased alanine aminotransferase (14% vs 3%). Treatment-related serious adverse events occurred in 25% of the camrelizumab plus rivoceranib group vs 7% of the sorafenib group, and 1 patient in each group experienced a treatment-related death. It was caused by multiple organ dysfunction syndrome in the investigational arm and respiratory failure and circulatory collapse in the control arm.

References

1. Hyeong-woo K. FDA hurdle cleared for liver cancer drug application: HLB. The Korea Herald. July 15, 2026. Accessed July 15, 2026. https://www.koreaherald.com/article/10809905
2. Elevar Therapeutics receives FDA complete response letter for combination of rivoceranib and camrelizumab as a first-line treatment for unresectable or metastatic hepatocellular carcinoma. News release. Elevar Therapeutics. July 10, 2026. Accessed July 15, 2026. https://tinyurl.com/2jdf9467
3. Announcement on receipt of complete response letter regarding camrelizumab for injection. News release. Jiangsu Hengrui Pharmaceuticals Co., Ltd. May 17, 2024. Accessed July 15, 2026. https://tinyurl.com/3kdz97k9
4. Ji-Yoon H. HLB, Antengene fail to gain U.S. FDA approval for liver cancer drug combo. News release. Chosun Biz. March 21, 2025. Accessed July 15, 2026. https://tinyurl.com/3jcd2j5m
5. Kim JH. HLB restarts FDA review with resubmitted liver cancer combo application. Korea Biomedical Review. January 26, 2026. Accessed July 15, 2026. https://tinyurl.com/3fddj45t
6. Elevar Therapeutics announces publication of CARES-310 study final analysis in The Lancet Oncology. News release. Elevar Therapeutics. December 3, 2026. Accessed July 15, 2026. https://tinyurl.com/yc7w9ahy