NCT06951646

ctDNA-MRD Guided Escalation of Ivonescimab and Docetaxel in Advanced NSCLC With Long-Term Responses to First-line Immunotherapy (CR1STAL-Adaptive)

ctDNA-MRD Guided Escalation of Ivonescimab and Docetaxel in Advanced NSCLC With Long-Term Responses to First-line Immunotherapy: a Randomized, Open-label, Phase II Trial (CR1STAL-Adaptive)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: Second Xiangya Hospital of Central South University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The CR1STAL-Adaptive study is a randomized, open-label, phase II multicenter interventional trial designed to evaluate the safety and efficacy of Ivonescimab (PD-1/VEGF bispecific antibody) combined with docetaxel versus standard treatment in patients with advanced NSCLC who have achieved long-term benefit from first-line immune checkpoint inhibitors (ICIs), but are ctDNA-MRD positive. Building upon insights from previous CR1STAL study (NCT05198154), the CR1STAL-Adaptive study supports the development of precision-guided, adaptive treatment strategies to delay progression and improve outcomes in NSCLC patients with a long-term response to immunotherapy. It represents a step forward in integrating dynamic molecular monitoring with individualized intervention strategies in the era of immunotherapy.

Conditions

• Non Small Cell Lung Cancer
• Immune Checkpoint Inhibitors (ICIs)

Interventions

Type	Name	Description
DRUG	Ivonescimab	For ctDNA-positive patients, escalation treatment will be administrated Ivonescimab: Intravenous infusion (IV), 20 mg/kg, Day 1, every 3 weeks (Q3W); All enrolled participants will continue treatment until one of the following occurs, whichever comes first: * The investigator determines that there is no longer clinical benefit (based on imaging assessments and clinical status) * Unacceptable toxicity * Completion of 24 months of treatment * Other discontinuation criteria specified in the protocol are met.
DRUG	Docetaxel	For ctDNA-positive patients, escalation treatment will be administrated Docetaxel: IV, 75 mg/m², Day 1, Q3W (The investigator may adjust the chemotherapy dose and schedule based on the patient's tolerance during treatment.) All enrolled participants will continue treatment until one of the following occurs, whichever comes first: * The investigator determines that there is no longer clinical benefit (based on imaging assessments and clinical status) * Unacceptable toxicity * Completion of 24 months of treatment * Other discontinuation criteria specified in the protocol are met.
OTHER	Standard Treatment group	For ctDNA-positive patients, continuing the original immunotherapy maintenance or immunotherapy combined with chemotherapy

Timeline

• Start date: 2026-03-10
• Primary completion: 2028-07-01
• Completion: 2030-06-01
• First posted: 2025-04-30
• Last updated: 2026-03-09

Locations

20 sites across 1 country: China