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

A Phase I/II Phase Evaluating 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.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Digestive System Tumors
• Intervention / Treatment: Drug: TQB3616 capsules＋ TQB2450 injection

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lin Shen, Master; Phone Number: 13911219511; Email: doctorshenlin@sina.cn
• Study Contact Backup: Name: shen; Email: doctorshenlin@sina.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
      • Contact: Shen Lin, Professor; Phone Number: 010-88196561; Email: doctorshenlin@sina.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: 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)

Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	Objective response rate refers to the percentage of complete (CR) or partial response (PR) subjects determined by the investigator based on RECIST 1.1 or iRECIST (CR under iRECIST criteria, PR can occur after imaging disease progression).	up to 48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate（DCR）	Disease control rate refers to the percentage of subjects with complete remission, partial remission, or stable disease (SD) of 6 weeks or more as determined by RECIST 1.1 or iRECIST (CR, PR, SD under iRECIST criteria can occur after imaging disease progression).	up to 48 weeks
Overall survival (OS)	Overall survival defined as the time from enrollment to death from any cause.	up to 48 weeks

Collaborators and Investigators

• Sponsor: Peking University
• Investigators: Study Chair: lin shen, master, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): November 24, 2021
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: November 11, 2021
• First Submitted That Met QC Criteria: November 24, 2021
• First Posted (Actual): December 1, 2021

Study Record Updates

• Last Update Posted (Actual): December 1, 2021
• Last Update Submitted That Met QC Criteria: November 24, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: PD-1/PD-L1 resistance; abnormal cell cycle
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms
• Other Study ID Numbers: TQB3616-TQB2450-I/II-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No