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

Sponsor
Second Xiangya Hospital of Central South University
Study ID
NCT06951646
Phase
PHASE2
Status
Recruiting
Apply to this trial

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Ivonescimab — DRUG
    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.
  • Docetaxel — DRUG
    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.
  • Standard Treatment group — OTHER
    For ctDNA-positive patients, continuing the original immunotherapy maintenance or immunotherapy combined with chemotherapy

Study Details

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.

Key Dates

Start date
Mar 10, 2026
Status verified
Mar 2026
Primary completion
Jul 1, 2028
Completion
Jun 1, 2030

Study Design

Enrollment
70 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Other: Standard Treatment
    For ctDNA-positive patients, the original maintenance treatment (eg. immunotherapy or immunotherapy combined with chemotherapy) will be continued.
  • Experimental: Escalation Treatment
    For ctDNA-positive patients, escalation treatment will be administrated

Primary Outcome Measure

Progression-Free Survival (PFS) in ctDNA-Positive Population [ Time Frame: 3 years ]

Central Contacts

Related Studies