Toripalimab Plus Chemo Meets PFS End Point in Frontline Advanced NSCLC

The addition of toripalimab to chemotherapy resulted in a significant improvement in progression-free survival (PFS) compared with chemotherapy alone when given as first-line treatment in patients with non–small cell lung cancer (NSCLC), meeting the primary end point of the phase 3 CHOICE-01 trial (NCT03856411).^1,2

At a data cutoff date of November 17, 2020, results from the interim analysis indicated that the median PFS per investigator assessment and RECIST v1.1 criteria in the toripalimab/chemotherapy arm was 8.3 months vs 5.6 months in the chemotherapy-alone arm (HR, 0.58; 95% CI, 0.44-0.77; P = .0001). The PFS rates at 1 year in the investigative and control arms were 32.6% and 13.1%, respectively.

Additionally, the PFS benefit with the toripalimab combination was reported both in those with squamous disease (HR, 0.55; 95% CI, 0.38-0.83) and those with non-squamous disease (HR, 0.59; 95% CI, 0.40-0.87), irrespective of PD-L1 expression.

The data from the interim analysis will be presented during the International Association for the Study of Lung Cancer 2021 World Conference on Lung Cancer.

“The CHOICE-01 study in patients with advanced NSCLC has demonstrated the clinical benefit of toripalimab in yet another first-line setting, building on the evidence of efficacy in first-line studies in nasopharyngeal carcinoma and esophageal squamous cell carcinoma,” Patricia Keegan, chief medical officer at Junshi Biosciences, stated in a press release. “With an excellent clinical profile being established across multiple tumor types, we expect to pursue registration for toripalimab for a broad array of indications in China, the United States, and other markets.”

In the randomized, double-blind, phase 3 CHOICE-01 trial enrolled patients with treatment-naïve, advanced NSCLC whose tumors did not harbor EGFR or ALK mutations. A total of 465 participants were randomized 2:1 to receive toripalimab at 240 mg (n = 309) or placebo (n = 156) plus chemotherapy every 3 weeks for 4 to 6 cycles. Those with squamous disease (n = 220) received paclitaxel plus carboplatin, and those with non-squamous disease (n = 245) received pemetrexed, cisplatin, and carboplatin.

This was followed by toripalimab plus placebo in those with squamous disease and toripalimab, placebo, and pemetrexed for those with non-squamous disease. Treatment was administered until progressive disease, unacceptable toxicity, or 2 years of therapy had been completed.

Patients were stratified based on PD-L1 expression on tumor cells, histopathology, and smoking status. Crossover to the toripalimab arm was permitted if patients on the chemotherapy-alone arm experienced progressive disease.

The primary end point of the trial was investigator-assessed PFS, and key secondary end points comprised blinded independent review committee (BICR)–assessed PFS, overall survival (OS), objective response rate (ORR), and duration of response (DOR).

At a median follow-up of 7.1 months in the investigative arm, and a median of 7.0 months in the control arm, a total of 218 PFS events were observed. PFS assessed by BICR demonstrated results that were comparable to those reported in the investigator assessment.

A better ORR was achieved with toripalimab plus chemotherapy vs chemotherapy alone in those with squamous disease, at 68.7% vs 58.9%, respectively, and those with non-squamous disease, at 58.6% vs 26.5%, respectively. The median DOR in the investigative and control arms in those with squamous disease were 6.9 months and 4.2 months, respectively; in those with nonsquamous disease, the median DORs were 8.6 months and 5.1 months, respectively.

As of March 7, 2021, the OS data were not yet mature; however, the trend favored the toripalimab arm. The median OS in the investigative and control arms was 21.0 months and 16.0 months, respectively (HR, 0.81; 95% CI, 0.57-1.17).

The toripalimab combination was reported to have a manageable safety profile, with no new signals noted. Grade 3 or higher adverse effects were experienced by 76.3% of those on the toripalimab/chemotherapy arm vs 80.1% on the chemotherapy-alone arm. Toxicities that resulted in treatment discontinuation were experienced by 12.3% and 1.9% of those on the investigative and control arms, respectively.

“The CHOICE-01 efficacy and safety data are compelling and demonstrate the potential for toripalimab to deliver the significant benefits of the PD-1 class of checkpoint inhibitor drugs to patients with NSCLC,” Ildiko Csiki, MD, PhD, chair of the Coherus Scientific Advisory Board and chief commercial research and development officer at City of Hope, stated in the press release. “As data accumulate in the pivotal studies in the broad clinical development program, toripalimab is showing itself to be an excellent checkpoint inhibitor. We eagerly anticipate results from additional phase 3 studies in esophageal, lung, liver, breast, kidney, bladder, stomach, and skin cancers.”

Junshi Biosciences and Coherus shared plans to meet with the FDA to discuss the submission of a biologics license application for toripalimab for use as a frontline treatment in patients with advanced NSCLC.

References

1. Junshi and Coherus Biosciences announce positive interim results of CHOICE-01, a phase 3 clinical trial evaluating toripalimab in combination with chemotherapy as first-lien treatment for non-small cell lung cancer. News release. August 18, 2021. Accessed August 19, 2021. https://bit.ly/3mil8n6
2. Wang J. CHOICE-01: a phase 3 study of toripalimab versus placebo in combination with first-line chemotherapy for advanced NSCLC. Presented at: International Association for the Study of Lung Cancer 2021 World Conference on Lung Cancer; September 8-11, 2021; Virtual. Abstract MA13.08. https://bit.ly/3iXPhWu