Clinical trial NCT05139082: 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
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Digestive System Tumors
Keywords: PD-1/PD-L1 resistance
abnormal cell cycle
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2021-12-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: PD-1/PD-L1 monoclonal antibody resistance, abnormal cell cycle, digestive system tumors
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: up to 48 weeks
Secondary outcomes:
measure: Disease control rate（DCR）
timeFrame: up to 48 weeks
measure: Overall survival (OS)
timeFrame: up to 48 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: lin shen, master
role: STUDY_CHAIR
References: