Addition of Toripalimab to Induction Improves PFS in Nonresectable NSCLC

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Induction toripalimab plus chemotherapy for 2 cycles, compared with chemotherapy alone, followed by definitive chemoradiotherapy and consolidation, significantly improved progression-free survival (PFS) in patients with bulky, unresectable stage III non–small cell lung cancer (NSCLC), according to data from the InTRist study (NCT05888402) presented at the 2025 ASCO Annual Meeting.1

“Toripalimab is a very promising strategy for patients with bulky, unresectable tumors. We observe the effective tumor reduction, significant PFS benefits and manageable toxicity,” Yu Wang, MD, PhD, of the Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, in Dongcheng, Beijing, China, said during a presentation of the data.

After a median follow-up of 14.7 months, the median PFS was not reached ([NR]; 95% CI, NR-NR) among patients treated with toripalimab induction therapy compared with 12.4 months (95% CI, 8.0-NR) in those treated with chemotherapy alone. The 1-year PFS rates were 85.6% (95% CI, 71.6%-100.0%) vs 54.5% (95% CI, 37.7%-78.7%), respectively, reducing the risk for disease progression or death by 74% (HR, 0.26; 95% CI, 0.08-0.81; P = .012).

Objective response rate (ORR) was significantly improved with toripalimab induction therapy at 77.8% compared with 40.0% with chemotherapy (P = .006). The toripalimab group demonstrated a disease control rate (DCR) of 96.3% compared with 92.0% with chemotherapy; however, this was not a statistically significant difference (P = .945).

The investigators observed no grade 4 or 5 pneumonitis. However, grade 1/2 pneumonitis occurred in 10 patients (37%) in the toripalimab arm, compared with 12 patients (48.0%) in the chemotherapy arm, while grade 3 events occurred in 3 patients (11.1%) and 1 patient (4.0%), respectively.

Frequent grade 1/2 immune-related adverse events in the toripalimab and chemotherapy-only arms included hypothyroidism (7.4% vs 8.0%, respectively), pruritis (11.1% vs 0%), sialadenitis (3.7% vs 0%), and myositis (3.7% vs 0%).

Induction Therapy With Toripalimab

“Based on our retrospective data, we found 2 cycles of induction immunotherapy plus chemotherapy could significantly decrease tumor value, which is very beneficial to subsequently thoracic radiation treatment planning,” Wang explained. “Also in the CheckMate-816 trial [NCT02998528],2 we found greater benefit from neoadjuvant nivolumab [Opdivo] in patients with stage IIIa [disease] compared to those with stage Ib or II disease. The selection of high-risk patients most likely to benefit from neoadjuvant immunotherapy would be very helpful.”

In the randomized, single-center phase 2 trial, patients were randomly assigned 1:1 to receive induction therapy with either 240 mg of toripalimab plus platinum-based double chemotherapy every 3 weeks for 2 cycles (n = 27) or platinum-based chemotherapy doublet chemotherapy every 3 weeks for 2 cycles (n = 25). Induction therapy was followed by definitive concurrent chemoradiotherapy, which was comprised of 60-66 Gy of thoracic radiation plus concurrent platinum-based doublet chemotherapy. For consolidation therapy, if patients had no progression, they received 240 mg toripalimab every 3 weeks for up to 1 year.

Key eligibility criteria included bulky (primary tumor size of ≥5 cm, or metastatic lymph nodes ≥2 cm), unresectable stage III NSCLC; EGFR/ALK wildtype disease; no prior anti-cancer treatment; and an ECOG performance status of 0 to 1.

PFS per RECIST v1.1 served as the primary end point. Secondary end points included overall survival (OS), ORR, duration of response, DCR, time to relapse, and safety.

The median age was 67 years (IQR, 60-70), and the majority of patients were male (96.2%), had an ECOG performance status of 1 (71.2%), and a smoking history (84.6%). Further, 74.1% of patients had stage IIIB disease at baseline, and 7.4% had stage IIIC NSCLC.

“We observe the promising efficacy, not only significantly higher after induction therapy, but also improving the PFS. The toxicity is manageable, and the phase 3 [randomized clinical trial] is being initiated,” Wang concluded.

References

1. Wang Y, Wang J, Deng L, et al. The preliminary results of a randomized phase II trial evaluating induction toripalimab plus chemotherapy followed by concurrent chemoradiotherapy and consolidation toripalimab in bulky unresectable stage III non-small-cell lung cancer (InTRist). J Clin Oncol. 2025;43(16):abstract 8012. doi:10.1200/JCO.2025.43.16_suppl.8012.
2. Neoadjuvant Opdivo (nivolumab) Plus Chemotherapy Significantly Improves Event-Free Survival in Patients with Resectable Non-Small Cell Lung Cancer in Phase 3 CheckMate -816 Trial. News release. Bristol Myers Squibb. Published November 8, 2021. Accessed June 2, 2025. https://news.bms.com/news/details/2021/Neoadjuvant-Opdivo-nivolumab-Plus-Chemotherapy-Significantly-Improves-Event-Free-Survival-in-Patients-with-Resectable-Non-Small-Cell-Lung-Cancer-in-Phase-3-CheckMate--816-Trial/default.aspx