CRC, HCC, NSCLC
Conditions
Brief summary
This is a Phase Ib/II , Open-label , Investigator-initiated Trail of SHR-1210 (an Anti-PD-1 Inhibitor) in Combination With SHR6390 (a CDK4/6 Inhibitor) in Patients With Advanced Colorectal Cancer, Non-small Cell Lung Cancer and Hepatocellular Carcinoma. The study was designed in two stages, the first stage was the tolerance observation stage, and the second stage was the curative effect expansion stage. The first part of the study is the Dose-finding Phase designed to establish the safety of SHR-1210 Combination With SHR6390 at different dose Levels(150mg QD or 100mg QD ). The second part of the study is the Expansion Phase designed to generate additional clinical data at specified doses . This study aims to evaluate the safety and efficacy of SHR-1210 combination with SHR6390 in the treatment of advanced CRC,NSCLC and HCC.
Interventions
DRUGSHR-1210
SHR-1210 was administered 200mg iv every 2 weeks
DRUGSHR6390
SHR6390 was administered 150mg or 100mg oral daily with 3 weeks on and 1 week off
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Harbin Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects voluntarily participate in this study and sign informed consent . * Men or women aged 18-75 years * Has confirmed by histology and cytology advanced and/or metastatic colorectal cancer patients, the advanced (Ⅲ B/Ⅳ period) in non-small cell lung cancer，Or patients with advanced hepatocellular carcinoma confirmed histologically or cytologically or clinically，At least one measurable lesion that meets the RECIST v1.1 criteria without local treatment. * The patients can swallow pills normally. * ECOG score was 0 or 1. * Have a life expectancy of at least 12 weeks. * The functions of vital organs meet the following requirements (excluding the use of any blood components and cytokines during screening) : Neutrophils≥1.5 x 109/L, Hb≥9g/dL; Plt≥90 x 109/L, ALB≥3g/dL, TSH≤ULN(Upper Limit Of Norma), TBIL ≤ 1.25 x ULN, ALT and AST ≤ 1.5 x ULN, AKP≤ 2.5 x ULN, CR≤ 1.5 x ULN * Female Subjects of childbearing potential must have a negative serum pregnancy test within 72 hours before the first dose and must be willing to use very efficient barrier methods of contraception for the course of the study through 3 months after the last dose of study treatment.
Exclusion criteria
* Subjects had any active autoimmune disease or history of autoimmune disease. * Subjects are using immunosuppressive agents, or systemic, or absorptive,local hormone therapy to achieve immunosuppression. It is still in use within 2 weeks before enrollment. * Subjects with severe allergic reactions to other monoclonal antibodies. * The subjects had a central nervous system metastases of clinical symptoms. * Central lung squamous cell carcinoma, or NSCLC with large vascular invasion confirmed by imaging. * A heart condition or disease that is not well controlled. * Subjects had active infections. * Other clinical trials of drugs were used within 4 weeks prior to the first administration. * The subjects have received other PD-1 antibody therapy or other immunotherapy for PD-1 / PD-L1 or CDK4/6 inhibitor treatment in the past. * There are other factors lead to patients can not participate in this clinical study by the judgment of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MTD /DLT (phase Ib) | Within four weeks after dosing | Maximum Tolerated Dose/Dose Limiting Toxicity |
| ORR(phase II) | from the first drug administration up to two years | Overall Response Rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CBR (phase Ib/II) | from the first drug administration up to last patients treatment for 6 months. | Clinical Benefit Rate |
| DoR (phase Ib/II) | from the first drug administration up to two years | Duration of response |
| ORR(phase Ib) | from the first drug administration up to two years | Overall Response Rate |
| TTR(phase Ib/II) | from the first drug administration up to one year | Time to Response |
| 12m-OS | 12 months after the first drug administration | 12 months Overall survival |
| PFS(phase Ib/II) | from the first drug administration up to two years | Progression-Free-Survival |
| Incidence of Treatment-Emergent Adverse Events (phase Ib/II) | from the first drug administration to within 90 days for the last SHR-1210 dose | adverse events/serious adverse events |
Contacts
Primary ContactYanqiao Zhang, PhD
Backup ContactGuangyu Wang, PhD
Outcome results
None listed