Toripalimab Plus Axitinib Meets PFS End Point in Unresectable or Distant Metastatic RCC

Jianjun Zou, MD, PhD

The combination of toripalimab and axitinib (Inlyta) improved progression-free survival (PFS) over single-agent sunitinib (Sutent) when used as first-line treatment in patients with intermediate to high risk, unresectable or distant metastatic renal cell carcinoma (RCC), meeting the primary end point of the phase 3 RENOTORCH trial (NCT04394975).¹

In a recent press release issued by Shanghai Junshi Biosciences Co., Ltd., it was noted that an independent data monitoring committee determined that the primary end point of PFS, as assessed by independent radiographic review (IRC) committee, met the prespecified efficacy boundary.

Additional data from the interim analysis of the trial showed that those who received the doublet also experienced an improved objective response rate (ORR), a key secondary end point, vs those who were given sunitinib monotherapy. No new safety signals were observed with toripalimab.

The data will be shared with regulatory authorities, and discussions regarding a supplemental new drug application seeking approval of the regimen for this patient population are planned. The findings from the analysis will also be presented at an upcoming medical meeting.

“This study represents a crucial milestone for our company as an innovative Chinese pharmaceutical company that aims to address the nation’s unmet medical needs,” Jianjun Zou, MD, PhD, president of Global Research and Development at Junshi Biosciences, stated in the press release. “We believe that RENOTORCH’s positive results will help bridge the gap in renal cancer PD-(L)1 immunotherapy in China, and we will take all the necessary steps to commercialize this achievement and provide new and effective combination immunotherapy options for domestic patients.”

The multicenter, randomized, open-label, active-controlled phase 3 trial enrolled patients with histologically confirmed, unresectable, recurrent or metastatic RCC with a clear cell component with or without sarcomatoid features who have not previously received systemic treatment.²

Patients were required to be between the ages of 18 years and 80 years, have an International Metastatic Database Consortium score of intermediate to high risk, at least 1 measurable disease by RECIST v1.1 criteria, and ECOG performance status of 0 or 1, and acceptable organ function.

A total of 421 participants were randomly assigned 1:1 to receive intravenous toripalimab at 240 mg every 3 weeks plus oral axitinib at a twice-daily dose of 5 mg or oral sunitinib at a daily dose of 50 mg for 4 weeks followed by 2 weeks off treatment or 50 mg once daily for 2 weeks followed by 1 week off treatment.^1,2 Treatment was continued until disease progression or unacceptable toxicity.¹

In addition to PFS by IRC serving as the study’s primary end point, secondary end points include investigator-assessed PFS, ORR by IRC or investigator assessment, duration of response, disease control rate, overall survival, and safety, among others.

The anti–PD-1 monoclonal antibody, toripalimab, is currently approved for 6 indications in China, including in select patients with unresectable or metastatic melanoma; recurrent or metastatic nasopharyngeal carcinoma (NPC); locally advanced or metastatic urothelial carcinoma; in combination with cisplatin/gemcitabine in locally recurrent or metastatic NPC; in combination with paclitaxel/cisplatin in unresectable locally advanced/recurrent or distant metastatic esophageal squamous cell carcinoma; in combination with pemetrexed/platinum in unresectable; and locally advanced or metastatic nonsquamous non–small cell lung cancer.

In July 2022, the FDA accepted for review the resubmission of the biologics license application seeking approval of toripalimab in combination with gemcitabine and cisplatin in the frontline treatment of patients with advanced recurrent or metastatic NPC, and as a single agent in the second- and later-line treatment of those with recurrent or metastatic NPC following platinum-based chemotherapy.3 The applications are supported by data from the phase 2 POLARIS-02 trial (NCT02915432) and the phase 3 JUPITER-02 trial (NCT03581786).

References

1. Junshi Biosciences announces primary endpoint met in RENOTORCH study of toripalimab for 1st-line treatment of advanced renal cell carcinoma. News release. Shanghai Junshi Biosciences, Ltd. April 27, 2023. Accessed April 27, 2023. https://www.globenewswire.com/news-release/
2. Study to evaluate the efficacy and safety of toripalimab in combination with axitinib versus sunitinib monotherapy in advanced renal cell cancer. ClinicalTrials.gov. Updated April 26, 2023. Accessed April 27, 2023. https://clinicaltrials.gov/ct2/show/NCT04394975
3. 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 April 27, 2023. https://investors.coherus.com/news-releases/news-release-details/