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

RECRUITINGPHASE2

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)

NCT06951646•Second Xiangya Hospital of Central South University

View on ClinicalTrials.gov

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.

Eligibility

Age

18 - 75 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Sign written informed consent prior to any study-related procedures, be willing and able to complete the visits, treatment regimen, and laboratory tests specified in the schedule, and comply with other requirements of the study;
•2. Aged ≥18 and ≤75 years old;
•3. ECOG PS score 0-1;
•4. Expected survival time ≥ 12 weeks;
•5. Patients with stage IIIB-IIIC and IV non-small cell lung cancer confirmed by histology or cytology that cannot be treated locally (TNM lung cancer staging of the 9th edition of the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer Classification);
•6. There must be no EGFR gene-sensitive mutation, ALK gene fusion or ROS1 gene fusion in non-squamous carcinoma
•7. Immunotherapy combined with platinum-containing doublet chemotherapy as a first-line standard treatment regimen;
•8. Non-PD with PFS at screening enrollment is 11 to 15 months;
•9. According to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1), it is recommended to have at least one measurable lesion, but patients without measurable lesions can still be included in the group (primary tumor recurrence or new metastatic lesions are considered PD).
•Participants with brain metastases who are asymptomatic or whose symptoms are stable after local treatment are allowed to enroll, as long as the participants meet the following conditions:
+10 more criteria

Exclusion Criteria

•1. Concurrent participation in another interventional clinical study or receipt of another investigational drug, unless participating in an observational clinical study；
•2. Systemic therapy with proprietary Chinese medicines with anti-tumor indications or immunomodulatory drugs (including thiopeptides, interferons, interleukins, except those used locally for the control of hydrothorax or ascites) within 2 weeks prior to the first dose；
•3. No measurable lesions as defined by RECIST 1.1 due to prior radical treatment (e.g., surgery or radiotherapy)
•4. Subjects who have received systemic antiangiogenic therapy;
•5. Subjects who are enrolled in another clinical study at the same time, unless it is a non-interventional clinical study or the follow-up period of an interventional study (defined as the time between the first dose of this study and the last dose of the previous clinical study being more than 4 weeks or more than 5 half-lives of other study drugs, whichever is shorter);
•6. During the screening period, imaging shows that the tumor surrounds important blood vessels or there is significant necrosis or cavity, and the investigator determines that entering the study will cause a risk of bleeding;
•7. Imaging findings during the screening period show that the tumor invades important peripheral organs and blood vessels (such as the heart and pericardium, trachea, esophagus, aorta, superior vena cava, etc.) or there is a risk of developing esophagotracheal fistula or esophagopleural fistula;
•8. Active autoimmune diseases requiring systemic treatment (such as treatment with disease-modifying drugs, corticosteroids, and immunosuppressants) within 2 years before the first dose (excluding irAEs caused by the use of PD-1/L1 inhibitors). Replacement therapy (such as thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a systemic treatment;
•9. A history of major diseases within 1 year before the first dose, specifically:
•* Unstable angina, myocardial infarction, congestive heart failure (NYHA classification ≥ Class 2) or vascular diseases (such as aortic aneurysm with a risk of rupture) that require hospitalization within 12 months before the first dose, or other cardiac damage that may affect the safety evaluation of the study drug (such as poorly controlled arrhythmia, myocardial ischemia, etc.);
+31 more criteria

Locations (20)

Hunan Cancer Hospital

Changsha, China

The Second Xiangya Hospital of Central South University

Changsha, China

The Third Hospital of Changsha

Changsha, China

Xiangya Hospital of Central South University

Changsha, China

Changsha Central Hospital

Changsha, China

The First Hospital of Changsha

Changsha, China

The Third Xiangya Hospital of Central South University

Changsha, China

Army Medical Center (Daping Hospital)

Chongqing, China

Guiyang Public Health Clinical Center

Guiyang, China

Faculty of Medicine, The Chinese University of Hong Kong

Hong Kong, China

Key Dates

Start Date

March 10, 2026

Primary Completion Date

July 1, 2028

Completion Date

June 1, 2030

Last Updated

March 9, 2026

Enrollment

ESTIMATED participants

Conditions

Non Small Cell Lung CancerImmune Checkpoint Inhibitors (ICIs)

Interventions

Ivonescimab

DRUG

Docetaxel

DRUG

Standard Treatment group

OTHER

Contacts

Fang Wu, MD, PhD

CONTACT

+86 13574858332 wufang4461@edu.csu.cn

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 9, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

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