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MRD and Imaging Guided Adaptive Neoadjuvant Therapy for Resectable NSCLC
Sponsor: Peking University People's Hospital
Summary
Neoadjuvant immunotherapy combined with platinum-based doublet chemotherapy has been established as the standard of care for driver-gene-negative (EGFR/ALK wild-type) stage II-IIIB non-small cell lung cancer (NSCLC), yielding pathological complete response (pCR) rates of 30-40%. Nevertheless, a substantial proportion of patients (approximately 60-70%) do not attain pCR, and strategies to further augment the pCR rate through treatment escalation remain an unmet clinical need. Accumulating evidence indicates that failure of ctDNA clearance and radiological stable disease (SD) following two cycles of neoadjuvant therapy are each robust predictors of unfavorable pathological response, and their combined assessment may enable accurate identification of the patient subset least likely to derive benefit from immunotherapy. This single-arm, proof-of-concept study will enroll patients with resectable or borderline resectable, EGFR/ALK wild-type, stage II-IIIB (N2) NSCLC. All participants will initially receive two cycles of a PD-1 inhibitor (nivolumab, pembrolizumab, toripalimab, or tislelizumab) in combination with platinum-based doublet chemotherapy. Following two cycles, patients will undergo ctDNA-MRD assessment and radiological evaluation. Patients in whom ctDNA has not cleared and whose radiological response is stable disease will be assigned to the treatment-escalation group and receive an intensified regimen comprising a PD-1 inhibitor plus anlotinib plus chemotherapy for cycles 3-4, whereas all remaining patients will continue the original regimen. Upon completion of neoadjuvant therapy, patients deemed resectable by a multidisciplinary team (MDT) will proceed to definitive surgery. The primary endpoint is the pCR rate in the treatment-escalation population. This study seeks to establish a precision escalation strategy guided by ctDNA-MRD in conjunction with imaging response, thereby providing an effective therapeutic approach for patients with NSCLC who respond poorly to immunotherapy and informing the design of subsequent confirmatory trials.
Official title: ctDNA-MRD and Imaging Response-Guided Adaptive Escalation of Neoadjuvant Therapy in Resectable and Borderline Resectable Non-Small Cell Lung Cancer: A Single-Arm, Proof-of-Concept Study
Key Details
Gender
All
Age Range
18 Years - Any
Study Type
INTERVENTIONAL
Enrollment
100
Start Date
2026-11-01
Completion Date
2030-08-01
Last Updated
2026-10-21
Healthy Volunteers
No
Conditions
Interventions
PD-1 inhibitor
One of four PD-1 inhibitors selected per patient: nivolumab 360 mg, pembrolizumab 200 mg, toripalimab 240 mg, or tislelizumab 200 mg, administered by intravenous infusion once every 3 weeks
Carboplatin
AUC 5 by intravenous infusion on day 1 of each 21-day cycle
Nab-paclitaxel
100 mg/m² by intravenous infusion on days 1 and 5 of each 21-day cycle. Used for squamous histology throughout all cycles, and for non-squamous histology in the treatment-escalation group (cycles 3-4), where it replaces pemetrexed
Pemetrexed
500 mg/m² by intravenous infusion on day 1 of each 21-day cycle (non-squamous histology). In the treatment-escalation group, pemetrexed is replaced by nab-paclitaxel during cycles 3-4
Anlotinib
12 mg orally once daily on days 1-14 of each 21-day cycle; added during cycles 3-4 in the treatment-escalation group
Locations (1)
Peking University People's Hospital
Beijing, Beijing Municipality, China