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

• ClinicalTrials.gov Identifier: NCT03711305
• Recruitment Status: Unknown
• First Posted: October 18, 2018
• Last Update Posted: April 18, 2022
• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Information provided by (Responsible Party): Jiangsu HengRui Medicine Co., Ltd.

Tracking Information

• First Submitted Date: October 16, 2018
• First Posted Date: October 18, 2018
• Last Update Posted Date: April 18, 2022
• Actual Study Start Date: December 30, 2018
• Estimated Primary Completion Date: October 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 14, 2022)

Duration of Overall Survival (OS) [ Time Frame: up to approximately 31 months ]

Baseline until death from any cause

Original Primary Outcome Measures (submitted: October 16, 2018)

• Duration of Progression-Free Survival (PFS) as Assessed by the Independent Review Committee Using RECIST v1.1 [ Time Frame: up to approximately 31 months ]
  Time Frame: Baseline until PD or death, whichever occurs first
• Duration of Overall Survival (OS) [ Time Frame: up to approximately 31 months ]
  Baseline until death from any cause

Current Secondary Outcome Measures (submitted: April 14, 2022)

• Duration of Progression-Free Survival (PFS) as Assessed Using RECIST v1.1 [ Time Frame: up to approximately 6 months ]
• Percentage of Participants With Objective Response (OR) as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: up to approximately 31 months ]
  Baseline until partial response (PR) or complete response (CR), whichever occurs first
• Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: up to approximately 31 months ]
  First occurrence of PR or CR until PD or death, whichever occurs first
• Percentage of Participants Alive and Without PD, as Assessed by the Investigator Using RECIST v1.1, at 6 Months and 1 Year [ Time Frame: 6 months, 1 year ]
• Percentage of Participants Alive at 1 Year and 2 Years [ Time Frame: 1 year, 2 years ]
• Percentage of Participants with Adverse Events Or Serious Adverse Events. [ Time Frame: up to approximately 31 months ]

Original Secondary Outcome Measures (submitted: October 16, 2018)

• Percentage of Participants With Objective Response (OR) as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: up to approximately 31 months ]
  Baseline until partial response (PR) or complete response (CR), whichever occurs first
• Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 [ Time Frame: up to approximately 31 months ]
  First occurrence of PR or CR until PD or death, whichever occurs first
• Percentage of Participants Alive and Without PD, as Assessed by the Investigator Using RECIST v1.1, at 6 Months and 1 Year [ Time Frame: 6 months, 1 year ]
• Percentage of Participants Alive at 1 Year and 2 Years [ Time Frame: 1 year, 2 years ]
• Percentage of Participants with Adverse Events Or Serious Adverse Events. [ Time Frame: up to approximately 31 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Carboplatin Plus Etoposide With or Without SHR-1316 in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)
• Official Title: Randomized, Double-blinded, Placebo Controlled, Multicenter, Phase III Study of Carboplatin Plus Etoposide With or Without SHR-1316 in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Extensive-stage Small Cell Lung Cancer

Intervention

• Drug: SHR-1316
  SHR-1316 intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6) and maintenance phase.
• Drug: Carboplatin
  Carboplatin intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6).
• Drug: Etoposide
  Etoposide intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6).
• Drug: Placebo
  Placebo intravenous infusion will be administered during the induction phase (Cycles 1-4 or 6) and maintenance phase.

Study Arms

• Experimental: 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.
  Interventions:

  • Drug: SHR-1316
  • Drug: Carboplatin
  • Drug: Etoposide
• Active Comparator: 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.
  Interventions:

  • Drug: Carboplatin
  • Drug: Etoposide
  • Drug: Placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: April 14, 2022): 462
• Original Estimated Enrollment (submitted: October 16, 2018): 396
• Estimated Study Completion Date: December 2023
• Estimated Primary Completion Date: October 2022 (Final data collection date for primary outcome measure)

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:• Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation

• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03711305
• Other Study ID Numbers: SHR-1316-III-301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Wei Shi; Jiangsu HengRui Medicine Co., Ltd.

• PRS Account: Jiangsu HengRui Medicine Co., Ltd.
• Verification Date: April 2022