Toripalimab Plus Chemo Elicits Significant OS Improvement in Recurrent or Metastatic Nasopharyngeal Carcinoma

First-line treatment with toripalimab in combination with gemcitabine and cisplatin resulted in a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) vs placebo plus chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma, according to data from the final OS analysis of the phase 3 JUPITER-02 trial (NCT03581786).^1,2

Data presented at the 2023 ASCO Annual Meeting showed that at a median follow-up of 36.0 months, patients treated with toripalimab plus chemotherapy (n = 146) experienced a median OS that was not evaluable (NE; 95% CI, 38.7 months–NE) vs 33.7 months (95% CI, 27.0-44.2) for those given placebo plus chemotherapy (n = 143; HR, 0.63; 95% CI, 0.45-0.89; P = .0083). The 3-year OS rates were 64.5% for the toripalimab arm and 49.2% for the placebo arm.

Additionally, toripalimab plus gemcitabine/cisplatin generated a median PFS of 21.4 months (95% CI, 11.7-NE) vs 8.2 months (95% CI, 7.0-9.8) for placebo plus gemcitabine/cisplatin (HR, 0.52; 95% CI, 0.37-0.73; nominal P < .0001). The 2-years PFS rates were 44.8% and 25.4% for the experimental and control arms, respectively.

“There are limited options for patients living with this very aggressive form of head and neck cancer. These results are remarkable, with meaningful improvement over chemotherapy alone, and this is practice-changing," Jennifer Choe, MD, PhD, assistant professor of Medicine and lead of the Head and Neck Medical Oncology Disease Team in the Division of Hematology and Oncology at Vanderbilt University Medical Center, stated in a news release.² "I was impressed with the primary end point outcome, extending PFS from 8.2 months with chemotherapy alone to 21.4 months with the addition of toripalimab, and now with the strong OS data, this will be a new standard of care for patients, if approved.”

Although gemcitabine-cisplatin chemotherapy is the international standard of care in the first-line setting for patients with recurrent or metastatic nasopharyngeal carcinoma, the use of toripalimab in combination with gemcitabine-cisplatin chemotherapy demonstrated a significant improvement in PFS in the previously reported interim analysis of JUPITER-02.³

In November 2021, the FDA accepted an initial biologics license application (BLA) for toripalimab in combination with gemcitabine and cisplatin for the first-line treatment of patients with recurrent or metastatic nasopharyngeal carcinoma.⁴ However, the regulatory agency issued a complete response letter in May 2022, citing the need for a quality process change.⁵

A revised BLA submission was accepted by the FDA in July 2022,⁶ and the BLA remains under review after the FDA was unable to conduct an on-site inspection of Junshi Biosciences’ manufacturing facility for toripalimab.⁷

JUPITER-02 enrolled patients between 18 and 75 years of age with histologically or cytologically confirmed recurrent or metastatic nasopharyngeal carcinoma that was not amenable for local regional treatment. Patients needed to have at least 1 measurable lesion and a life expectancy of 3 or more months.⁸

Exclusion criteria consisted of a history of sever hypersensitivity to monoclonal antibodies; prior anti–PD-1, anti–PD-L1, or anti–CTLA-4 therapy; or a major surgical procedure not related to nasopharyngeal carcinoma within 28 days prior to randomization.

Evaluable patients were randomly assigned in a 1:1 fashion to receive 240 mg of toripalimab or placebo in combination with gemcitabine and cisplatin once every 3 weeks for up to 6 cycles, followed by single-agent toripalimab or placebo once every 3 weeks until disease progression, intolerable toxicity, or completion of 2 years of treatment. Additionally, patients were stratified by ECOG performance status (0 vs 1) and extent of disease (recurrent vs primary metastatic) at enrollment.

The primary end point of the trial was PFS by blinded independent review committee. Secondary end points included OS, overall response rate (ORR) by blinded independent review committee, PFS by investigator, duration of response, and safety. Notably, PFS, ORR, and OS, were tested hierarchically.

Additional data from the OS analysis showed that among 46% and 40% of patients who experienced disease progression in the toripalimab and placebo ingroups, respectively, received subsequent anti–PD-1 and anti–PD-L1 therapies.

The OS benefits of toripalimab were generally consistent across subgroups. However, among patients with metastatic disease (n = 117), the OS analysis did not demonstrate a benefit (HR, 1.23; 95% CI, 0.701-2.175; P = .4648). PFS benefits were observed for the toripalimab regimen across all subgroups.

References

1. Mai HQ, Chen QY, Chen DP, et al. Final overall survival analysis of JUPITER-02: a phase 3 study of toripalimab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC). J Clin Oncol. 2023;41(suppl 16):6009. doi:10.1200/JCO.2023.41.16_suppl.6009
2. Coherus announces positive final overall survival results of JUPITER-02 phase 3 trial evaluating toripalimab in nasopharyngeal carcinoma. News release. Coherus BioSciences. June 5, 2023. Accessed June 14, 2023. https://investors.coherus.com/news-releases/news-release-details/coherus-announces-positive-final-overall-survival-results
3. Xu R-H, Mai H-Q, Chen Q-Y, et al. JUPITER-02: randomized, double-blind, phase III study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC). J Clin Oncol. 2021;39(suppl 15):LBA2. doi:10.1200/JCO.2021.39.15_suppl.LBA2
4. Coherus and Junshi Biosciences announce FDA acceptance of BLA filing for toripalimab for treatment of nasopharyngeal carcinoma. News release. Coherus BioSciences, Inc. and Shanghai Junshi Biosciences Co., Ltd. November 1, 2021. Accessed June 14, 2023. https://investors.coherus.com/news-releases/news-release-details/coherus-and-junshi-biosciences-announce-fda-acceptance-bla
5. Coherus and Junshi Biosciences receive complete response letter from US FDA for toripalimab BLA. News release. Coherus BioSciences Inc. May 2, 2022. Accessed June 14, 2023. https://investors.coherus.com/news-releases/news-release-details/coherus-and-junshi-biosciences-receive-complete-response-letter
6. Coherus and Junshi Biosciences announce FDA acceptance of resubmission of BLA for toripalimab for the treatment of nasopharyngeal carcinoma. News release. Coherus BioSciences. July 6, 2022. Accessed June 14, 2023. https://investors.coherus.com/news-releases/news-release-details/coherus-and-junshi-biosciences-announce-fda-acceptance
7. Coherus and Junshi Biosciences share update on the FDA review of the biologics license application (BLA) for toripalimab as treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC). News release. Coherus BioSciences and Junshi Biosciences. December 24, 2022. Accessed June 14, 2023. https://investors.coherus.com/news-releases/news-release-details/coherus-and-junshi-biosciences-share-update-fda-review-biologics
8. The efficacy and safety study of toripalimab injection combined with chemotherapy for nasophapyngeal cancer. ClinicalTrials.gov. Updated April 18, 2022. Accessed June 14, 2023. https://www.clinicaltrials.gov/ct2/show/NCT03581786