Study of Carboplatin Plus Etoposide With or Without SHR-1316 in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)

NCT ID: NCT03711305

Last Updated: 2022-04-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 462 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-30
• Study Completion Date: 2023-12-31

Brief Summary

This randomized, double-blinded, placebo-controlled phase III, multicenter study is designed to evaluate the safety and efficacy of SHR-1316 in combination with carboplatin plus (+) etoposide compared with treatment with placebo + carboplatin + etoposide in chemotherapy-naive participants with ES-SCLC.

Detailed Description

Participants will be randomized in a 1:1 ratio to receive either SHR-1316 + carboplatin + etoposide or placebo + carboplatin + etoposide for 4-6 cycles in the induction phase followed by maintenance with SHR-1316 or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Treatment can be continued until persistent radiographic PD or or unacceptable toxicity.

Conditions

Extensive-stage Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

SHR-1316 + carboplatin + etoposide

Participants will receive SHR-1316 intravenously in combination with carboplatin and etoposide during the induction phase (Cycles 1-4 or 6). Thereafter, participants will receive maintenance (after induction phase) SHR-1316 until persistent radiographic PD, intolerable toxicity or withdrawal of consent.

Group Type: EXPERIMENTAL

SHR-1316

Intervention Type: DRUG

SHR-1316 intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6) and maintenance phase.

Carboplatin

Intervention Type: DRUG

Carboplatin intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6).

Etoposide

Intervention Type: DRUG

Etoposide intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6).

Placebo + carboplatin + etoposide

Participants will receive placebo intravenously in combination with carboplatin and etoposide during the induction phase (Cycles 1-4 or 6). Thereafter, participants will receive maintenance (after induction phase) placebo until persistent radiographic PD, intolerable toxicity or withdrawal of consent.

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

Carboplatin intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6).

Etoposide

Intervention Type: DRUG

Etoposide intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6).

Placebo

Intervention Type: DRUG

Placebo intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6) and maintenance phase.

Interventions

SHR-1316

SHR-1316 intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6) and maintenance phase.

Intervention Type: DRUG

Carboplatin

Carboplatin intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6).

Intervention Type: DRUG

Etoposide

Etoposide intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6).

Intervention Type: DRUG

Placebo

Placebo intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6) and maintenance phase.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age >= 18 years and <= 75 years
• Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system)
• Eastern Cooperative Oncology Group performance status of 0 or 1
• No prior systemic treatment or immune checkpoint inhibitor treatment for ES-SCLC
• At least 6 months treatment-free period since last chemo/radiotherapy with curative intent for limited-stage SCLC
• Measurable disease, as defined by RECIST v1.1
• Adequate hematologic and end organ function
• Patients must submit a pre-treatment tumor tissue sample during the study.
• Signed inform consent form

Exclusion Criteria

• Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for ≥ 1 week prior to randomization
• Leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Uncontrolled or symptomatic hypercalcemia
• Malignancies other than SCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
• History of autoimmune disease, including but not limited to myasthenia gravis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease
• Prior treatment with immune checkpoint blockade therapies
• Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first administration of study treatment. Inhaled or topical steroids, and adrenal replacement steroid are permitted in the absence of active autoimmune disease.
• Significant cardiovascular disease
• Prior allogeneic bone marrow transplantation or solid organ transplant
• Treatment with systemic immunosuppressive medications within 2 weeks prior to randomization
• History of hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, carboplatin or etoposide
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu HengRui Medicine Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wei Shi

Role: STUDY_DIRECTOR

Jiangsu HengRui Medicine Co., Ltd.

Locations

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Jilin Cancer Hospital

Jilin, Changchun, China

Countries

China

References

Long Y, Wang H, Xie X, Li J, Xu Y, Zhou Y. Updated cost-effectiveness analysis of adebrelimab plus chemotherapy for extensive-stage small cell lung cancer in China. BMJ Open. 2024 Apr 5;14(4):e077090. doi: 10.1136/bmjopen-2023-077090.

Reference Type: DERIVED

PMID: 38582540 (View on PubMed)

Wang J, Zhou C, Yao W, Wang Q, Min X, Chen G, Xu X, Li X, Xu F, Fang Y, Yang R, Yu G, Gong Y, Zhao J, Fan Y, Liu Q, Cao L, Yao Y, Liu Y, Li X, Wu J, He Z, Lu K, Jiang L, Hu C, Zhao W, Zhang B, Shi W, Zhang X, Cheng Y; CAPSTONE-1 Study Group. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Jun;23(6):739-747. doi: 10.1016/S1470-2045(22)00224-8. Epub 2022 May 13.

Reference Type: DERIVED

PMID: 35576956 (View on PubMed)

Other Identifiers

SHR-1316-III-301

Identifier Type: -

Identifier Source: org_study_id