How should postoperative treatment be selected after neoadjuvant chemoimmunotherapy, particularly when surgery reveals residual disease? And can analysis of the tumor immune microenvironment help identify patients most likely to benefit from a particular perioperative approach?
These questions frame this overview of two studies in resectable non-small cell lung cancer (NSCLC). NCT07039656 investigates adjuvant toripalimab plus chemotherapy in populations defined by previous neoadjuvant treatment and pathological response. CTONG1804 evaluates perioperative nivolumab strategies alongside exploratory analyses of tumor and circulating immune cells.
In the lead-up to ESMO 2026, these studies provide an opportunity to examine two complementary directions in immunotherapy research: tailoring postoperative treatment to the preceding clinical course and investigating the biological determinants of benefit. The discussion below focuses on study design and clinical rationale.
NCT07039656: Adjuvant Toripalimab After Upfront Surgery or Neoadjuvant Chemoimmunotherapy
NCT07039656 is a multicenter, open-label, nonrandomized phase II trial evaluating toripalimab plus platinum-based chemotherapy followed by toripalimab maintenance in completely resected NSCLC. The planned enrollment is 211 patients.
The study separates two clinically distinct populations. Cohort 1 includes patients with stage IB–IIIB disease who underwent surgery without neoadjuvant treatment. Cohort 2 includes patients with stage IIB–III disease who received neoadjuvant chemoimmunotherapy and either did not achieve a major pathological response (MPR) or achieved MPR but retained pathological lymph node involvement.
Patients receive three to four cycles of chemotherapy with toripalimab, followed by toripalimab maintenance. Toripalimab is administered every three weeks for a planned total of 17 cycles. The primary endpoint is two-year disease-free survival; secondary endpoints include overall survival and treatment-related adverse events.
The second cohort is particularly relevant to postoperative decision-making. It investigates additional chemoimmunotherapy in patients selected on the basis of their pathological response to preoperative treatment. This raises a specific therapeutic question: can further exposure to chemotherapy and PD-1 blockade provide meaningful disease control in this population, with an acceptable treatment burden?
The distinction between the cohorts is essential. Treatment after upfront surgery and further treatment after neoadjuvant chemoimmunotherapy involve different prior exposures and selection criteria. Outcomes should therefore be interpreted within each cohort, rather than as a direct comparison of the two treatment pathways.
Without a randomized control arm, the study cannot isolate the contribution of postoperative chemotherapy or establish superiority over alternative adjuvant strategies. It can, however, provide prospective estimates of disease-free survival and toxicity to inform subsequent comparative trials.
Toripalimab (Loqtorzi): Uses in Cancer, Side Effects, Dosage, Expectations, and More
CTONG1804: Perioperative Nivolumab and the Search for Immune Biomarkers
CTONG1804 (NCT04015778) is an exploratory phase II study in China evaluating nivolumab monotherapy or nivolumab combined with nab-paclitaxel and carboplatin before surgery, as well as postoperative nivolumab, in patients with high-risk resectable NSCLC.
Alongside efficacy and safety, the study incorporates characterization of the tumor immune microenvironment and circulating immune cells. Its translational objective is to investigate biological features associated with therapeutic response and toxicity.
This component extends the study’s relevance beyond the activity of an individual regimen. Analysis of tumor tissue and peripheral blood offers an opportunity to examine how local immune characteristics relate to systemic immune responses and clinical outcomes. Such observations may generate hypotheses about why patients receiving similar treatment experience different degrees of benefit.
The inclusion of nivolumab alone and chemoimmunotherapy also raises the question of treatment intensity. However, determining which patients require chemotherapy alongside PD-1 blockade demands more than identifying associations between immune features and response. The interpretation depends on treatment allocation, cohort comparability, sample size, and the statistical design.
Likewise, a biomarker associated with favorable outcomes is not necessarily predictive of benefit from a specific therapy. Independent validation and prospective testing would be required before candidate markers could guide chemotherapy omission or selection of a perioperative regimen.
From Exploratory Evidence to Treatment Individualization
The two studies address different components of the same clinical challenge. NCT07039656 examines a postoperative strategy defined by prior treatment and pathological response. CTONG1804 investigates whether immune characterization can help explain variation in benefit and toxicity.
Their value will depend on how effectively these observations inform the next generation of trials. For postoperative treatment, that means comparative evaluation of specific strategies within clearly defined patient populations. For immune biomarkers, it means demonstrating that a test can improve treatment selection. Both approaches ultimately need to connect biological or pathological findings with durable disease control and an acceptable burden of treatment.
