IBI310 (Anti-CTLA-4) in Combination With Sintilimab in Patients With Non-small-cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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This is an open label, multicenter, phase Ib study evaluating IBI310 (anti-CTLA-4) in combination with Sintilimab in patients with advanced, recurrent or metastatic non-small-cell lung cancer (NSCLC)

Official Title
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An Open Label, Multicenter, Phase Ib Study Evaluating IBI310 (Anti-CTLA-4) in Combination With Sintilimab in Patients With Advanced, Recurrent or Metastatic Non-small-cell Lung Cancer (NSCLC)

Conditions
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NSCLC (Non-small-cell Lung Cancer)

Intervention / Treatment
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* Drug: Sintilimab
* Drug: IBI310


Participation Criteria
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Eligibility Criteria
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Eligibility Criteria: Aged ≥18 years; ECOG 0   1; Histologically /cytologically confirmed R/M NSCLC; Adequate organ and bone marrow function; Expected survival ≥12 weeks; Female subjects of childbearing age or male patients whose sex partners are women of childbearing age should take effective contraceptive measures throughout the treatment period and within 6 months after the last administration; Subjects who sign the written informed consent form, and can abide by the visits and related procedures specified in the protocol. At least 1 measurable lesion according to the Response Evaluation Criteria in Solid Tumors Version 1.1(RECIST V1.1). Exclusion Criteria: Had tumors other than NSCLC within the past 5 years. Had allogeneic organ or stem cell transplantation. The presence of uncontrolled life-threatening illness Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Patients who have used large doses of glucocorticoids, anti-cancer monoclonal antibodies, and other immunosuppressive agents within 4 weeks. HIV positive. Patients with significantly lower heart, liver, lung, kidney and bone marrow function. Severe, uncontrolled medical conditions and infections. At the same time using other test drugs or in other clinical trials. Refusal or inability to sign informed consent to participate in the trial. Other treatment contraindications. Emotional disturbance or mental illness, no civil capacity or limited capacity for civil conduct. Hepatitis B surface antigen (HBsAg) positive and HBVDNA ≥1000cps/ml. Patients with positive HCV antibody test results can only be included in the study when the polymerase chain reaction of HCV RNA is negative.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBI310 (anti-CTLA-4) 1mg/kg(Q3W until progressive disease)in combination with Sintilimab<br>The test group will be treated with IBI310 1mg/kg IV, Q3W+ Sintilimab 200 mg IV, Q3W until progressive disease,intolerable toxicity, start of a new antitumor treatment, withdrawal of informed consent, loss to follow-up, death or other situations requiring termination of treatment specified in the protocol, whichever occurs first. | Drug: Sintilimab<br>* (IBI310 1mg/kg IV, Q3W+ Sintilimab 200 mg IV, Q3W)until progressive disease,intolerable toxicity, start of a new antitumor treatment, withdrawal of informed consent, loss to follow-up, death or other situations requiring termination of treatment specified in the protocol, whichever occurs first.<br>Drug: IBI310<br>* (IBI310 1mg/kg IV, Q3W+ Sintilimab 200 mg IV, Q3W) until progressive disease,intolerable toxicity, start of a new antitumor treatment, withdrawal of informed consent, loss to follow-up, death or other situations requiring termination of treatment specified in the protocol, whichever occurs first.<br>|
| Experimental: IBI310 (anti-CTLA-4) 1mg/kg(Q3W*4cycles)in combination with Sintilimab<br>The test group will be treated with IBI310 1mg/kg IV, Q3W+ Sintilimab 200 mg IV, Q3W*4cycles,and then Sintilimab 200 mg IV, Q3W single until progressive disease,intolerable toxicity, start of a new antitumor treatment, withdrawal of informed consent, loss to follow-up, death or other situations requiring termination of treatment specified in the protocol, whichever occurs first. | Drug: Sintilimab<br>* (IBI310 1mg/kg IV, Q3W+ Sintilimab 200 mg IV, Q3W)until progressive disease,intolerable toxicity, start of a new antitumor treatment, withdrawal of informed consent, loss to follow-up, death or other situations requiring termination of treatment specified in the protocol, whichever occurs first.<br>Drug: IBI310<br>* (IBI310 1mg/kg IV, Q3W+ Sintilimab 200 mg IV, Q3W) until progressive disease,intolerable toxicity, start of a new antitumor treatment, withdrawal of informed consent, loss to follow-up, death or other situations requiring termination of treatment specified in the protocol, whichever occurs first.<br>|
| Experimental: IBI310 (anti-CTLA-4) 1mg/kg(Q6W)in combination with Sintilimab<br>The test group will be treated with IBI310 1mg/kg IV, Q6W+ Sintilimab 200 mg IV, Q3Wuntil progressive disease,intolerable toxicity, start of a new antitumor treatment, withdrawal of informed consent, loss to follow-up, death or other situations requiring termination of treatment specified in the protocol, whichever occurs first. | Drug: Sintilimab<br>* (IBI310 1mg/kg IV, Q3W+ Sintilimab 200 mg IV, Q3W)until progressive disease,intolerable toxicity, start of a new antitumor treatment, withdrawal of informed consent, loss to follow-up, death or other situations requiring termination of treatment specified in the protocol, whichever occurs first.<br>Drug: IBI310<br>* (IBI310 1mg/kg IV, Q3W+ Sintilimab 200 mg IV, Q3W) until progressive disease,intolerable toxicity, start of a new antitumor treatment, withdrawal of informed consent, loss to follow-up, death or other situations requiring termination of treatment specified in the protocol, whichever occurs first.<br>|
| Experimental: IBI310 (anti-CTLA-4) 0.5mg/kg in combination with Sintilimab<br>The test group will be treated with IBI310 0.5mg/kg IV, Q3W+ Sintilimab 200 mg IV, Q3W until progressive disease,intolerable toxicity, start of a new antitumor treatment, withdrawal of informed consent, loss to follow-up, death or other situations requiring termination of treatment specified in the protocol, whichever occurs first. | Drug: Sintilimab<br>* (IBI310 1mg/kg IV, Q3W+ Sintilimab 200 mg IV, Q3W)until progressive disease,intolerable toxicity, start of a new antitumor treatment, withdrawal of informed consent, loss to follow-up, death or other situations requiring termination of treatment specified in the protocol, whichever occurs first.<br>Drug: IBI310<br>* (IBI310 1mg/kg IV, Q3W+ Sintilimab 200 mg IV, Q3W) until progressive disease,intolerable toxicity, start of a new antitumor treatment, withdrawal of informed consent, loss to follow-up, death or other situations requiring termination of treatment specified in the protocol, whichever occurs first.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate(ORR) | Investigator evaluated ORR per RECIST V1.1 | Up to 2 years | 
| Treatment Emergent Adverse Event (TEAE) | Incidence and severity of treatment-emergent: which is evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, v5.0) grade; | Up to 2 years | 
| Severe Adverse Event (SAE) | Incidence and severity of treatment-emergent: which is evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, v5.0) grade; | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DOR | Defined as the time from the first documented objective response to the first documented progressive disease or death of any cause, whichever occurs first; | Up to 2 years | 
| Progression Free Survival (PFS) | Defined as the time from randomization to the first documented progressive disease or death of any cause, whichever occurs first; | Up to 2 years | 
| Overall Survival (OS) | Defined as the time from randomization to death of any cause in subjects without receiving any immunotherapy outside the study protocol for first-line treatment of advanced NSCLC | Up to 2 years | 
| Disease Control Rate (DCR) | Defined as the proportion of patients whose best response is CR, PR, and stable disease (SD) non-CR/non-PD | Up to 2 years | 
| Time to Response (TTR) | Defined as the time from randomization to the first documented and confirmed objective response (CR or PR) | Up to 2 years | 
| HRQoL | According to EORTC QLQ-C30 | Up to 2 years |