Study of CDK4/6 Inhibitor Combined With PD-L1 Monoclonal Antibody in the Treatment of PD-1/PD-L1 Resistance and Abnormal Cell Cycle Digestive System Tumors

NCT ID: NCT05139082

Last Updated: 2021-12-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-24
• Study Completion Date: 2023-10-01

Brief Summary

This study intends to explore the effectiveness and safety of CDK4/6 inhibitor (TQB3616) combined with PD-L1 monoclonal antibody (TQB2450) in the treatment of PD-1/PD-L1 monoclonal antibody resistance and abnormal cell cycle digestive system tumors, through prospective Explore to provide more evidence-based medical evidence for precision immunotherapy for patients with digestive system tumors.

Conditions

Digestive System Tumors

Keywords

PD-1/PD-L1 resistance; abnormal cell cycle

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CDK4/6 inhibitor (TQB3616) + PD-L1 monoclonal antibody (TQB2450)

TQB3616 capsules (120/150/180mg p.o. qd, d1-d21) combined with TQB2450 injection (1200mg ivgtt, d1)

Group Type: OTHER

TQB3616 capsules＋ TQB2450 injection

Intervention Type: DRUG

TQB3616 is a highly active CDK4/6 inhibitor. Preclinical studies have shown that it has a strong inhibitory effect on the kinase activity of CDK4/6.

TQB2450 is a humanized monoclonal antibody targeting PD-L1, which prevents PD-L1 from binding to the PD-1 and B7.1 receptors on the surface of T cells, so as to restore the activity of T cells and thereby enhance the immune response, and has the potential to treat various types of tumors.

Interventions

TQB3616 capsules＋ TQB2450 injection

TQB3616 is a highly active CDK4/6 inhibitor. Preclinical studies have shown that it has a strong inhibitory effect on the kinase activity of CDK4/6.

TQB2450 is a humanized monoclonal antibody targeting PD-L1, which prevents PD-L1 from binding to the PD-1 and B7.1 receptors on the surface of T cells, so as to restore the activity of T cells and thereby enhance the immune response, and has the potential to treat various types of tumors.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Voluntary participation and written informed consent;

2. Age ≥ 18 years old;

3. No gender limitation;

4. Digestive system malignant tumor diagnosed by pathology;

5. Digestive system tumor patients who have failed standard treatment;

6. Patients with PD-1 monoclonal antibody or PD-L1 monoclonal antibody treatment failure;

7. Abnormal cell cycle signaling pathways

8. Patients with unresectable digestive system tumors confirmed by imaging;

9. There is at least one measurable lesion (according to the RECIST1.1 standard) or an unmeasurable lesion that can be evaluated, and the imaging diagnosis is ≤21 days from the selection time；

10. The expected survival period is ≥3 months;

11. General physical status (ECOG) 0-2;

12. Sufficient bone marrow hematopoietic function (within 7 days);

13. Heart, lung, kidney, and liver functions are generally normal.

14. Women of childbearing age should agree to use effective contraceptive measures during the study period and 6 months after the end of the study, and have a negative serum or urine pregnancy test within 7 days before enrollment in the study; men should agree to use effective contraception during the study period and after the end of the study period 6 Effective contraceptive measures must be used within one month.

Exclusion Criteria

1. People who are currently receiving other effective treatments;

2. Patients who are using immunosuppressive agents or systemic or absorptive local hormone therapy to achieve immunosuppression within 2 weeks before the first medication;

3. Patients who have participated in other clinical trials within 4 weeks before enrollment;

4. Allergic to study drugs; 5 . Those without measurable tumor lesions, such as body cavity effusion or diffuse infiltration of organs;

6. Those with measurable lesions that have received radiotherapy. 7. Patients with other primary malignant tumors other than digestive system tumors at the same time, except for early solid tumors that have been cured for more than 1 year; 8. Clinically significant cardiovascular diseases, such as heart failure (NYHAIII-IV), are not controlled A history of coronary heart disease, cardiomyopathy, arrhythmia, uncontrolled hypertension or myocardial infarction within the past 1 year; 9. Neurological or mental disorders that affect cognitive ability, including central nervous system metastasis; 10. Existed within 14 days before enrollment Active severe clinical infections (>grade 2 NCI-CTCAE version 5.0), including active tuberculosis; 11. Known or self-reported HIV infection or active hepatitis B or C; 12. Uncontrolled Systemic diseases, such as poorly controlled diabetes; 13. A history of interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or evidence of interstitial lung disease on baseline chest X-ray/CT; 14. Keratitis , Ulcerative keratitis or severe dry eye; 15. Known hypersensitivity or allergic reaction to any component of the study drug; 16. Pregnancy (determined by serum β-chorionic gonadotropin test) or breast-feeding.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University

OTHER

Sponsor Role: lead

Responsible Party

Shen Lin

Beijing Cancer Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

lin shen, master

Role: STUDY_CHAIR

Peking University Cancer Hospital & Institute

Locations

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Countries

China

Central Contacts

Lin Shen, master

Role: CONTACT

Phone: 13911219511

Email: doctorshenlin@sina.cn

shen

Role: CONTACT

Email: doctorshenlin@sina.cn

Facility Contacts

Shen Lin, Professor

Role: primary

Other Identifiers

TQB3616-TQB2450-I/II-01

Identifier Type: -

Identifier Source: org_study_id