A Trial of SHR-1210 in Combination With SHR6390 in Patients With Advanced CRC, NSCLC and HCC

A Phase Ib/II , Open-label , Investigator-initiated Trail of An Anti-PD-1 Inhibitor SHR-1210 in Combination With A CDK4/6 Inhibitor SHR6390 in Patients With Advanced Colorectal Cancer, Non-small Cell Lung Cancer and Hepatocellular Carcinoma

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.

Study Overview

• Status: Unknown
• Conditions: HCC; NSCLC; CRC
• Intervention / Treatment: Drug: SHR-1210; Drug: SHR6390

• Study Type: Interventional
• Enrollment (Anticipated): 41
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yanqiao Zhang, PhD; Phone Number: 138 4512 0210; Email: yanqiaozhang@126.com
• Study Contact Backup: Name: Guangyu Wang, PhD; Phone Number: 18249038966; Email: 18249038966@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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
Experimental: SHR-1210 + SHR6390; SHR-1210 was administered 200mg iv every 2 weeks in combination with SHR6390 150mg or 100mg oral daily with 3 weeks on and 1 week off	Drug: SHR-1210; SHR-1210 was administered 200mg iv every 2 weeks; Drug: SHR6390; SHR6390 was administered 150mg or 100mg oral daily with 3 weeks on and 1 week off

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR(phase II)	Overall Response Rate	from the first drug administration up to two years
MTD /DLT (phase Ib)	Maximum Tolerated Dose/Dose Limiting Toxicity	Within four weeks after dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR(phase Ib)	Overall Response Rate	from the first drug administration up to two years
Incidence of Treatment-Emergent Adverse Events (phase Ib/II)	adverse events/serious adverse events	from the first drug administration to within 90 days for the last SHR-1210 dose
CBR (phase Ib/II)	Clinical Benefit Rate	from the first drug administration up to last patients treatment for 6 months.
DoR (phase Ib/II)	Duration of response	from the first drug administration up to two years
PFS(phase Ib/II)	Progression-Free-Survival	from the first drug administration up to two years
TTR(phase Ib/II)	Time to Response	from the first drug administration up to one year
12m-OS	12 months Overall survival	12 months after the first drug administration

Collaborators and Investigators

• Sponsor: Harbin Medical University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: yanqiao zhang, phD, Harbin Medical University Cancer Hosptital

Study record dates

Study Major Dates

• Study Start (Anticipated): July 30, 2018
• Primary Completion (Anticipated): July 30, 2019
• Study Completion (Anticipated): July 30, 2020

Study Registration Dates

• First Submitted: July 13, 2018
• First Submitted That Met QC Criteria: July 24, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): July 26, 2018
• Last Update Submitted That Met QC Criteria: July 24, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: SHR-1210-SHR6390-IIT

Drug and device information, study documents

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