Toripalimab induction therapy combined with chemotherapy has demonstrated significant clinical benefits in patients with bulky, unresectable stage III non-small cell lung cancer (NSCLC), according to results from the randomized phase 2 InTRist study presented at the 2025 American Society of Clinical Oncology Annual Meeting.
The study showed that two cycles of toripalimab induction therapy plus chemotherapy, followed by definitive chemoradiotherapy and consolidation, led to substantially improved progression-free survival compared to chemotherapy alone in this challenging patient population.
Significant Progression-Free Survival Benefits
After a median follow-up of 14.7 months, patients receiving toripalimab induction therapy achieved a median progression-free survival that was not reached, compared to 12.4 months in the chemotherapy-only group. The 1-year PFS rates were 85.6% versus 54.5%, respectively, representing a 74% reduction in the risk of disease progression or death (HR 0.26; 95% CI, 0.08-0.81; P=0.012).
"Toripalimab is a very promising strategy for patients with bulky, unresectable tumors. We observe the effective tumor reduction, significant PFS benefits and manageable toxicity," said Yu Wang, MD, PhD, from the Department of Radiation Oncology at National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.
Enhanced Response Rates
The objective response rate was significantly higher with toripalimab induction therapy at 77.8% compared to 40.0% with chemotherapy alone (P=0.006). The disease control rate reached 96.3% in the toripalimab group versus 92.0% with chemotherapy, though this difference was not statistically significant (P=0.945).
Study Design and Patient Population
The randomized, single-center phase 2 trial enrolled 52 patients who were randomly assigned 1:1 to receive either 240 mg of toripalimab plus platinum-based doublet chemotherapy every 3 weeks for 2 cycles (n=27) or platinum-based doublet chemotherapy alone for 2 cycles (n=25). Following induction therapy, all patients received definitive concurrent chemoradiotherapy consisting of 60-66 Gy of thoracic radiation plus concurrent platinum-based doublet chemotherapy.
Patients without disease progression continued with consolidation therapy of 240 mg toripalimab every 3 weeks for up to 1 year. Key eligibility criteria included bulky disease (primary tumor size ≥5 cm or metastatic lymph nodes ≥2 cm), unresectable stage III NSCLC, EGFR/ALK wildtype disease, no prior anticancer treatment, and ECOG performance status of 0 to 1.
The median patient age was 67 years, with 96.2% being male, 71.2% having an ECOG performance status of 1, and 84.6% having a smoking history. Stage IIIB disease was present in 74.1% of patients, while 7.4% had stage IIIC NSCLC.
Safety Profile
The treatment demonstrated a manageable safety profile with no grade 4 or 5 pneumonitis events observed. Grade 1/2 pneumonitis occurred in 10 patients (37%) in the toripalimab arm compared to 12 patients (48%) 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%), pruritis (11.1% vs 0%), sialadenitis (3.7% vs 0%), and myositis (3.7% vs 0%).
Clinical Rationale and Future Directions
Wang explained the clinical rationale behind the approach: "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. Also in the CheckMate-816 trial, we found greater benefit from neoadjuvant nivolumab 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."
The study's primary endpoint was progression-free survival per RECIST v1.1, with secondary endpoints including overall survival, objective response rate, duration of response, disease control rate, time to relapse, and safety.
"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, indicating the advancement of this treatment strategy to larger-scale validation studies.
