Actively Recruiting

Phase 2
Age: 18Years - 75Years
All Genders
NCT06951646

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

Led by Second Xiangya Hospital of Central South University · Updated on 2026-03-09

70

Participants Needed

20

Research Sites

220 weeks

Total Duration

On this page

Sponsors

S

Second Xiangya Hospital of Central South University

Lead Sponsor

N

Nanjing Shihejiyin Technology, Inc.

Collaborating Sponsor

AI-Summary

What this Trial Is About

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

Official Title

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

Who Can Participate

Age: 18Years - 75Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Signed informed consent and able to comply with study visits and tests
  • Age between 18 and 75 years
  • ECOG performance status 0-1
  • Expected survival of at least 12 weeks
  • Confirmed stage IIIB, IIIC, or IV non-small cell lung cancer not eligible for local treatment
  • No EGFR-sensitive mutation, ALK fusion, or ROS1 fusion in non-squamous carcinoma
  • Previous first-line standard treatment with immunotherapy plus platinum-containing chemotherapy
  • Non-progressive disease with progression-free survival of 11 to 15 months at screening
  • At least one measurable lesion or documented disease progression by RECIST 1.1 criteria
  • Asymptomatic or stable brain metastases after local treatment with specific conditions
  • Adequate laboratory values for blood counts, liver, kidney, coagulation, and cardiac function
  • Negative pregnancy test for women of childbearing potential and use of contraception during and after treatment
  • Male participants must use effective contraception during and after treatment
Not Eligible

You will not qualify if you...

  • Participation in another interventional clinical trial or investigational drug use recently
  • Use of systemic anti-tumor proprietary Chinese medicines or immunomodulators within 2 weeks
  • No measurable lesions due to prior radical treatments
  • Prior systemic antiangiogenic therapy
  • Tumors with high risk of bleeding or invading vital organs increasing risk
  • Active autoimmune disease requiring recent systemic treatment
  • Major cardiovascular, liver, pulmonary, or metabolic diseases within the past year
  • Recent gastrointestinal perforation, obstruction, or major surgery
  • Recent radiotherapy with unresolved toxicity
  • Recent live vaccines or severe infections
  • History of bleeding disorders or recent significant bleeding
  • Immunodeficiency or positive HIV test
  • Active hepatitis B or C infection
  • Active tuberculosis or syphilis infection
  • Allergy to study drugs or severe hypersensitivity to monoclonal antibodies
  • Use of long-term systemic corticosteroids or immunosuppressants
  • History of mental illness, substance abuse, or uncontrolled toxicity from previous cancer treatments
  • Symptomatic central nervous system metastases or carcinomatous meningitis
  • Other active malignancies unless in complete remission
  • Pregnancy or breastfeeding
  • Other illnesses or laboratory abnormalities increasing risks or interfering with study participation

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 20 locations

1

Hunan Cancer Hospital

Changsha, China, 410011

Not Yet Recruiting

2

The Second Xiangya Hospital of Central South University

Changsha, China, 410011

Actively Recruiting

3

The Third Hospital of Changsha

Changsha, China, 410011

Not Yet Recruiting

4

Xiangya Hospital of Central South University

Changsha, China, 410011

Not Yet Recruiting

5

Changsha Central Hospital

Changsha, China

Not Yet Recruiting

6

The First Hospital of Changsha

Changsha, China

Not Yet Recruiting

7

The Third Xiangya Hospital of Central South University

Changsha, China

Not Yet Recruiting

8

Army Medical Center (Daping Hospital)

Chongqing, China

Not Yet Recruiting

9

Guiyang Public Health Clinical Center

Guiyang, China

Not Yet Recruiting

10

Faculty of Medicine, The Chinese University of Hong Kong

Hong Kong, China

Not Yet Recruiting

11

Kiang Wu Hospital, Macao

Macao, China

Not Yet Recruiting

12

The First Affiliated Hospital of Nanchang University

Nanchang, China

Not Yet Recruiting

13

The First Affiliated Hospital of Guangxi Medical University

Nanning, China

Not Yet Recruiting

14

Liaoning Cancer Hospital and Institute

Shenyang, China

Not Yet Recruiting

15

Shanxi Bethune Hospital

Taiyuan, China

Not Yet Recruiting

16

Hubei Cancer Hospital

Wuhan, China

Not Yet Recruiting

17

Renmin Hospital of Wuhan University

Wuhan, China

Not Yet Recruiting

18

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, China

Not Yet Recruiting

19

The First Affiliated Hospital of Xinxiang Medical University

Xinxiang, China

Not Yet Recruiting

20

Zhuzhou Central Hospital

Zhuzhou, China

Not Yet Recruiting

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Research Team

F

Fang Wu, MD, PhD

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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