Frontline Toripalimab Plus Chemotherapy Approved in China for Advanced Nonsquamous NSCLC

The China National Medical Products Administration has approved the supplemental new drug application seeking the approval of toripalimab plus pemetrexed and platinum as a frontline treatment in patients with unresectable, locally advanced or metastatic, nonsquamous non–small cell lung cancer (NSCLC) who do not harbor EGFR mutations or ALK fusions.¹

The application is supported by findings from the phase 3 CHOICE-01 trial (NCT03856411), in which the toripalimab combination was found to significantly improve progression-free survival (PFS) and overall survival (OS) over chemotherapy alone in this patient population, irrespective of PD-L1 expression status.

As of October 31, 2021, the median PFS achieved with the addition of toripalimab to chemotherapy was 9.7 months vs 5.5 months with chemotherapy alone, translating to a 52% reduction in the risk of disease progression or death in 245 patients with nonsquamous NSCLC (HR, 0.48; 95% CI, 0.35-0.66; P < .0001).¹ The median OS with toripalimab/chemotherapy was not yet reached; the toripalimab resulted in a 52% reduction in the risk of death (HR, 0.48; 95% CI, 0.32-0.71).¹

“We are pleased that toripalimab’s first indication for the treatment of lung cancer has been approved, which means we will be able to help more patients fight against malignant tumors with the highest incidence and mortality rates in China,” Dr Jianjun Zou, president of Global Research and Development at Junshi Biosciences, stated in a press release.

Patients with advanced squamous and nonsquamous NSCLC who had treatment-naïve, locally advanced, or metastatic disease were enrolled to CHOICE-01.² They were required to have measurable disease by RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and tumor tissue available for PD-L1 expression evaluation. Those who harbored sensitizing EGFR mutations or ALK fusions were excluded.

Study participants were randomly assigned 1:1 to receive toripalimab at 240 mg intravenously (IV; n = 309) or IV placebo (n = 156) on day 1 of every 3-week cycle for up to 2 years. In both arms, those with nonsquamous disease were also given pemetrexed at 500 mg/m² on day 1 plus cisplatin at 75 mg/m² on day 1/carboplatin at area under the curve 5 on day 1 for 4 to 6 cycles, followed by pemetrexed. Those with squamous disease also received nab-paclitaxel (Abraxane) at 100 mg/m² on days 1, 8, and 15 in combination with carboplatin for 4 to 6 cycles.

Participants who had progressive disease on the chemotherapy-alone arm were allowed to crossover to receive the toripalimab combination.

The primary end point of the trial was PFS by RECIST v1.1 criteria and investigator review. OS, PFS by blinded independent review committee assessment, overall response rate, duration of response, disease control rate, time to response, and safety, all served as secondary end points.

The most recent findings from the trial were shared at the 2022 ASCO Annual Meeting and showed that in those with a tumor PD-L1 expression of at least 50%, the median PFS was 10.3 months with toripalimab/chemotherapy (n = 72) vs 5.6 months with chemotherapy alone (n = 28; HR, 0.45; 95% CI, 0.27-0.78). In these patients, the 12-month PFS rate in the investigative arm was 46.4% vs 20.3% in the control arm.

Among those with a tumor PD-L1 expression of less than 50%, the median PFS with toripalimab/chemotherapy (n = 128) was 8.4 months vs 6.7 months with chemotherapy alone (n = 75; HR, 0.56; 95% CI, 0.40-0.78).³ In the investigative and control arms, the PFS rates at 12 months were 39.4% and 20.8%, respectively. In those with a tumor PD-L1 expression of less 1%, the median PFS with toripalimab/chemotherapy (n = 98) and chemotherapy alone (n = 41) was 8.2 months and 5.6 months, respectively (HR, 0.47; 95% CI, 0.32-0.71); the 12-month PFS rates were 25.9% and 10.3%, respectively.

For those with unknown PD-L1 status, the median PFS with toripalimab plus chemotherapy (n = 11) was 8.4 months vs 5.5 months with chemotherapy alone (n = 12; HR, 0.62; 95% CI, 0.21-1.79). The 12-month PFS rates in these arms were 37.5% and 11.4%, respectively.

In those with high tumor mutational burden (TMB) who received toripalimab plus chemotherapy (n = 77), the median PFS was 13.1 months vs 5.5 months in those who received chemotherapy alone (n = 45; HR, 0.34; 95% CI, 0.21-0.54). The 12-month PFS rates in the investigative and control arms were 52.5% and 15.3%, respectively. The median OS rate had not yet been reached in the investigative arm vs 41.1% in the control arm (HR, 0.67; 95% CI, 0.38-1.19); the 24-month OS rates were 52.2% and 41.1%, respectively.

For those with a low TMB who received toripalimab/chemotherapy (n = 187), the median PFS was 8.3 months vs 6.5 months with chemotherapy alone (n = 85; HR, 0.62; 95% CI, 0.46-0.83); the 12-months PFS rates were 32.8% and 18.5%, respectively. Here, the median OS was not evaluable vs 16.2 months in the investigative and control arms, respectively (HR, 0.68; 95% CI, 0.47-0.98); the 24-month OS rates were 51.3% and 35.0%, respectively.

The toripalimab combination was found to have a manageable toxicity profile, irrespective of PD-L1 status.

References

1. Junshi Biosciences receives NMPA approval of sNDA for toripalimab in combination with chemotherapy as first-line treatment for advanced nonsquamous non-small cell lung cancer. News release. Shanghai Junshi Biosciences Co., Ltd. September 20, 2022. Accessed September 20, 2022. https://bit.ly/3UpKmOT
2. Wang J. Final progression-free survival, interim overall survival and biomarker analyses of CHOICE-01: a phase 3 study of toripalimab versus placebo in combination with first-line chemotherapy for advanced NSCLC without EGFR/ALK mutations. J Clin Oncol. 2022;40(suppl 36):362936. doi:10.1200/JCO.2022.40.36_suppl.362936
3. Wang J. Updates on abstract 362936: final progression-free survival, interim overall survival, and biomarker analyses of CHOICE-01: A phase III study of toripalimab versus placebo in combination with first-line chemotherapy for advanced NSCLC without EGFR/ALK mutations. Presented at: 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract 362936