Background
Phase II, open-label RCT (NADIM II). N=172 patients with resectable stage IIIA or IIIB (T3-4N2) NSCLC per UICC 8th edition, ECOG PS 0–1, no actionable molecular alteration. First randomized perioperative nivolumab + chemotherapy trial in resectable stage III NSCLC. 1:1 randomization.
Interventions and follow up
Arm A: Nivolumab 360 mg IV q3wk + carboplatin AUC6 + paclitaxel 200 mg/m² q3wk × 3 cycles → surgery → nivolumab 480 mg q4wk × 5 cycles adjuvant (N=86)
Arm B: Carboplatin AUC6 + paclitaxel 200 mg/m² q3wk × 3 cycles → surgery (N=86)
Primary endpoint: Pathological complete response (pCR) at surgery
mFollow up: 24 mo
Arm B: Carboplatin AUC6 + paclitaxel 200 mg/m² q3wk × 3 cycles → surgery (N=86)
Primary endpoint: Pathological complete response (pCR) at surgery
mFollow up: 24 mo
Results
pCR: 36.8% vs 6.9%, RR 5.34, 95% CI 1.34–21.23, P=.002
MPR (≤10% viable tumor): 52.9% vs 13.9%
PFS: HR 0.48, 95% CI 0.26–0.88, P=.017
OS (descriptive): HR 0.45, 95% CI 0.25–0.81
MPR (≤10% viable tumor): 52.9% vs 13.9%
PFS: HR 0.48, 95% CI 0.26–0.88, P=.017
OS (descriptive): HR 0.45, 95% CI 0.25–0.81
Adverse events
Overall: grade ≥3 AEs 50.6% (nivo+chemo) vs 31.0% (chemo).
Immune-related: grade ≥3 ~10% (pneumonitis, colitis, hepatitis).
Surgical: surgery completed 93% vs 91%.
Immune-related: grade ≥3 ~10% (pneumonitis, colitis, hepatitis).
Surgical: surgery completed 93% vs 91%.
Conclusions
Perioperative nivolumab + chemotherapy resulted in significantly higher pCR (37% vs 7%) and improved PFS vs chemotherapy alone in resectable stage III NSCLC. The OS trend (HR 0.45) is promising but requires phase III confirmation given the trial's phase II design.
Key Limitations
Phase II trial — not powered for OS as a primary endpoint; all survival analyses are exploratory. N=172 limits statistical precision. Carboplatin/paclitaxel backbone differs from CheckMate 816 (cisplatin + histology-specific partner), limiting cross-trial comparison. Includes stage IIIB (T3-4N2), a more advanced subgroup than other perioperative IO trials. Adjuvant nivolumab only in experimental arm creates treatment asymmetry beyond neoadjuvant.
Clinical Context
NADIM II provides phase II support for perioperative nivolumab in resectable stage III NSCLC, complementing the phase III CheckMate 816 (neoadjuvant nivo+chemo, EFS benefit), CheckMate 77T, and KEYNOTE-671 (both perioperative, OS benefit). Perioperative IO + chemo is now FDA-approved via multiple agents for resectable early/stage III NSCLC. ESMO-MCBS: not scored (phase II).