Adaptive adjuvant sintilimab treatment guided by MRD for resected Stage II–IIIB NSCLC

Adaptive Adjuvant Sintilimab Therapy Guided by MRD in II-IIIB Stage NSCLC Patients With Non-pCR Pathological Response After Neoadjuvant Immunotherapy Combined With Chemotherapy: a Prospective, Multi-center, Single-arm, Phase II Trial

This trial tests whether using postoperative blood MRD tests to guide adjuvant sintilimab helps people with resected Stage II–IIIB NSCLC who did not achieve a complete response after neoadjuvant chemo‑immunotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 115 (estimated)
• Ages: 28 Years to 75 Years
• Sex: All
• Sponsor: Guangdong Association of Clinical Trials (Academic / other)
• Drugs / interventions: sintilimab, chemotherapy, immunotherapy, prednisone
• Locations: 2 sites (Guangzhou, Guangdong and 1 other locations)
• Trial ID: NCT07120698 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open‑label Phase II study enrolling patients with resected Stage II–IIIB NSCLC who remain non‑pCR after neoadjuvant PD‑1 inhibitor plus chemotherapy. MRD blood tests are done 3–7 days and about 28 days after surgery to determine the next steps: patients with persistent or positive MRD receive adjuvant sintilimab 200 mg IV every 3 weeks, while those with consecutive negative MRD undergo observation. All participants are followed every 3 months with chest CT and MRD testing; sintilimab is started if MRD becomes positive during follow‑up and stopped if MRD converts to negative. The trial is conducted at Guangdong Provincial People's Hospital and the Third People's Hospital of Chengdu with collaborating regional centers.

Who should consider this trial

Good fit: Adults 18–75 years with histologically confirmed resectable Stage II–IIIB NSCLC (non‑massive/resectable N2) who received 3–4 cycles of neoadjuvant PD‑1 inhibitor plus chemotherapy, had R0 resection, and did not achieve a pathological complete response are ideal candidates.

Not a fit: Patients with a pathological complete response after neoadjuvant therapy, unresectable or non‑R0 disease, or those medically unable to receive sintilimab or attend the participating centers are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, MRD‑guided adjuvant sintilimab could catch early residual disease and target immunotherapy to patients most likely to benefit, potentially reducing recurrences and avoiding unnecessary treatment.

How similar studies have performed: Adjuvant PD‑1 therapies and MRD‑guided approaches have shown promise in some cancers and in select NSCLC settings, but MRD‑guided adjuvant immunotherapy in resected NSCLC remains relatively novel with limited definitive evidence.

Eligibility criteria

Inclusion Criteria:

1. Signed written informed consent prior to the initiation of any trial-related procedures.
2. Male or female aged ≥18 years and ≤75 years.
3. Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).
4. Received 3-4 cycles of neoadjuvant immunotherapy (PD-1 inhibitor) combined with chemotherapy.
5. Underwent radical surgical treatment (R0), with surgical procedures including lobectomy or sleeve lobectomy. All gross tumors must be completely resected at the end of surgery, and all surgical margins of the resected tumors must be negative. Systemic lymph node dissection is required.
6. Clinical stage II, IIIA, or IIIB (limited to resectable N2) according to the AJCC 8th edition TNM classification for lung cancer. Resectable N2 refers to non-massive (defined as short-axis diameter \<3 cm), discrete, or single-station N2 involvement. If clinically suspected of N2 or N3, pathological confirmation is recommended whenever feasible.
7. Patients with pathological response assessment of 1%-90% residual viable tumor (RVT).
8. No EGFR mutations, ROS1 fusions, ALK fusions, or RET fusions. Other potentially targetable driver gene alterations will be determined in consultation with the sponsor.
9. No prior anti-tumor treatment other than PD-1 inhibitors and chemotherapy before radical surgery for lung cancer.
10. Completed radical surgery for lung cancer 4-12 weeks prior to study enrollment, with pathological confirmation of R0 resection and radiological evidence of no residual tumor foci 1 month after radical surgery.
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
12. Life expectancy \>6 months.
13. Adequate organ function:

1\. Absolute neutrophil count (ANC) ≥1.5×10\^9/L without the use of granulocyte colony-stimulating factor within the past 14 days.

2\. Platelets ≥100×10\^9/L without transfusion within the past 14 days. 3. Hemoglobin \>9 g/dL without transfusion or use of erythropoiesis-stimulating agents within the past 14 days.

4\. Total bilirubin ≤1.5× upper limit of normal (ULN). 5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN (subjects with liver metastases are allowed to have ALT or AST ≤5×ULN).

6\. Serum creatinine ≤1.5×ULN and creatinine clearance (calculated using the Cockcroft-Gault formula) ≥60 ml/min.

7\. Good coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN.

8\. Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. Subjects with baseline TSH outside the normal range are eligible if total T3 (or free T3) and free T4 are within the normal range.

9\. Cardiac enzyme profile within the normal range (subjects with isolated laboratory abnormalities deemed not clinically significant by the investigator are also eligible).

14\. For female subjects of childbearing potential, a negative urine or serum pregnancy test must be obtained within 3 days prior to the first administration of the study drug (Day 1 of Cycle 1). If the urine pregnancy test result is inconclusive, a serum pregnancy test is required. Postmenopausal women are defined as those who have been amenorrheic for at least 1 year, or those who have undergone surgical sterilization or hysterectomy.

15\. All subjects (regardless of gender) at risk of conception must use contraception with a failure rate of less than 1% per year throughout the treatment period until 120 days after the last administration of the study drug (or 180 days after the last administration of chemotherapy).

16\. Provide samples for MRD assessment (surgical tissue + blood).

Exclusion Criteria:

1. Diagnosis of any malignancy other than non-small cell lung cancer within 5 years prior to the first dose (excluding completely treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or carcinoma in situ that has been completely resected).
2. Received adjuvant radiotherapy prior to dosing.
3. Patients who underwent pneumonectomy.
4. Currently participating in an interventional clinical study or received other investigational drugs or used investigational devices within 4 weeks prior to the first dose.
5. Received neoadjuvant treatment with anti-tumor therapies other than chemotherapy and immunotherapy.
6. Presence of unhealed surgical incisions, ulcers, or fractures.
7. In the investigator's opinion, severe concomitant systemic diseases that may affect the subject's ability to complete the study. Subjects with positive autoimmune antibodies must be assessed and confirmed by the investigator to have no autoimmune diseases requiring systemic treatment before enrollment.
8. Presence of primary immunodeficiency diseases.
9. Receiving systemic corticosteroid therapy within 7 days prior to the first dose of the study (excluding intranasal, inhaled, or other topical corticosteroids). Note: The use of physiologic doses of corticosteroids (≤10 mg/day prednisone or equivalent) is permitted.
10. Known allogeneic organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
11. Known allergy to the active ingredient or excipients of the study drug, sintilimab.
12. Not fully recovered from toxicities and/or complications caused by any prior interventions prior to the start of treatment (i.e., ≤Grade 1 or returned to baseline, excluding fatigue or alopecia).

Where this trial is running

Guangzhou, Guangdong and 1 other locations

• Guangdong Provincial People's Hospital — Guangzhou, Guangdong, China (Recruiting)
• The third people's hospital of chengdu — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Principal investigator: Yang — Guangdong Association of Clinical Trials
• Study coordinator: Yi Yang

Conditions NSCLC; MRD; II-IIIB Stages; Adjuvant Immunotherapy; II-IIIB stages; adjuvant immunotherapy