Safety and Tolerability Evaluation of Low-dose Radiation in Combination With CS1001 in Relapsed SCLC Patients

Study Overview
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Brief Summary
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A Phase Ia/Ib Safety and Tolerability Evaluation of Low-dose Radiation in Combination with CS1001 in relapsed SCLC patients

Detailed Description
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This is a dose-escalation study of Low-dose Radiation in combination with CS1001 in relapsed SCLC patients. Patients are assigned to 3 treatment groups received from 3 Gy to 15Gy, to determine the safety, tolerability and the maximal tolerant dose. Biomarkers and immunological markers are collected and analyzed as well.

Official Title
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A Phase Ia/Ib, Open-Label, Multiple-Dose, Dose-Escalation and Expansion Study of the Anti-PD-L1 Monoclonal Antibody CS1001 in Subjects With Advanced Solid Tumors

Conditions
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Relapsed Small Cell Lung Cancer

Intervention / Treatment
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* Drug: CS1001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically or cytologically confirmed LS-SCLC or ES-SCLC and experienced progression since first-line standard platinum containing dual-drug chemotherapy. Patients whose initial diagnosis was limited must undergo radical chest radiotherapy and the time of tumor progression is not less than 3 months from the end of radiotherapy, or cannot receive radical chest radiotherapy due to specific reasons At least one extracranial measurable lesion (RECIST v1.1), and for a lesion that has received radiotherapy, progression of the lesion after radiotherapy must be confirmed. Patients with brain metastases are allowed to receive previous radiotherapy and their condition is stable, but the time to the end of radiotherapy must not be less than 3 months. No radiotherapy contraindications were judged by the radiologist ECOG performance status of 0 or 1. Patients with life expectancy ≥ 3 months. Patients must have adequate organ function. Fertile men and women of childbearing potential must agree to use an effective method of birth control from providing signed consent and for 6 months after last study drug administration. Exclusion Criteria: Subjects known to have primary CNS tumors or meningeal metastases or unstable CNS metastases. Patients with active autoimmune diseases or history of autoimmune diseases should be excluded. Patients who have received immune checkpoint proteins/antibody/medicine (including PD-1, PD-L1, etc) for treatment. Known history of HIV infection. Subjects with active chronic hepatitis B or active hepatitis C . Patients who have serious hypersensitive reaction to monoclonal antibodies, and have history of uncontrolled allergic asthma. Known history of alcoholism or drugs abuse. Subjects with history of radiation pneumonitis of grade 3 or above, regardless of recovered or not.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: low-dose radiation+CS1001<br>low-dose radiation+CS1001 | Drug: CS1001<br>* low-dose radiation+CS1001 1200mg Q3W. In the dose escalation part, the dose levels will be escalated following a modified 3+3 dose escalation scheme. Dose A: 3Gy/1f; Dose B: 9Gy/3f; Dose C: 15Gy/5f; In the dose expansion part, more SCLC patients will be assigned.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the recommended radiation dose and preliminarily evaluate the anti-tumor efficacy of CS1001 in combination with low-dose radiotherapy in subjects with limited or extensive stage SCLC who failed the firstline treatment |  | From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AE) and Dose-Limiting Toxicity (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) V4.03 |  | From first dose to 30 days after last dose of CS1001, up to 2 years. | 
| Cmax: Peak concentration, the maximum drug concentration measured during one dosing cycle |  | From first dose to 30 days after last dose of CS1001, up to 2 years. | 
| The number and percentage of subjects with detectable Anti-drug Antibody (ADA) |  | From first dose to 30 days after last dose of CS1001, up to 2 years. |