Camrelizumab Combined With Apatinib ,Carboplatin and Etoposide in Participants With ES-SCLC

A Single -Arm, Open-label, Multicenter Phase II Study of Camrelizumab Combined With Apatinib ,Carboplatin and Etoposide in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC)

This single-arm, Phase II, multicenter study was designed to evaluate the safety and efficacy of Camrelizumab (anti-programmed death-receptor 1 [PD-1] antibody) in combination with Apatinib+carboplatin plus (+) etoposide in chemotherapy-naive participants with ES-SCLC. Participants will be receive camrelizumab +apatinib+ carboplatin + etoposide on 21-day cycles for four -six cycles in the induction phase followed by maintenance with camrelizuab +apatinib 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 symptomatic deterioration.

Study Overview

• Status: Not yet recruiting
• Conditions: Small-cell Lung Cancer
• Intervention / Treatment: Drug: camrelizumab; Drug: Apatinib Mesylate; Drug: Carboplatin; Drug: Etoposide

• Study Type: Interventional
• Enrollment (Anticipated): 69
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 and 70 years old
• Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system);
• No prior systemic treatment for ES-SCLC；
• Has received radiotherapy and chemotherapy for limited stage SCLC must have received definitive treatment, and has at least 6 months of no treatment interval from the last treatment to the diagnosis of extensive SCLC
• Eastern Cooperative Oncology Group performance status of 0 or 1；
• life expectancy≥ 12 weeks
• Adequate hematologic and organ function
• Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 90 days after the last dose of study (such as intrauterine devices , contraceptives or condoms) ; No pregnant or breastfeeding women, and a negative pregnancy test are received within 72h before the first dose of the study.

Exclusion Criteria:

• Has prior therapy with apatinib,anlotinib, anti-programmed cell death (PD)-1, anti-PD-L1 or other immunotherapy against PD-1/PD-L1;
• Has active or untreated central nervous system (CNS) metastases and/or cancerous meningitis;
• Has spinal cord compression which was not cured or relieved through surgery and/or radiotherapy, or diagnosed spinal cord compression after treatment showed no clinical evidence of disease stabilization prior to allocation ≥1 week;
• Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with blood vessels is unclear;
• Active autoimmune diseases requiring systemic treatment occurred within 2 years prior to first administration ;
• Immunosuppressive therapy with immunosuppressive agents or systemic or absorbable local hormones (dosage > 10 mg/day prednisone or other therapeutic hormones) is required for the purpose of immunosuppression, and is still in use for 2 weeks after the first administration;
• Has arterial or venous thromboembolic events occurred within 6 months, such as cerebrovascular accident including transient ischemic attack, deep vein thrombosis and pulmonary embolism;
• Within 3 months prior to initial administration, subjects with evidence of bleeding had clinical significance or history of bleeding tendency, regardless of severity;
• Has vaccinated with vaccines or attenuated vaccines within 4 weeks prior to first administration
• Has major surgical procedure、biopsy or obvious traumatic injury within 28 days before allocation;
• Has participated in other anticancer drug clinical trials within 4 weeks;
• Has diagnosed and/or treated additional malignancy within 5 years prior to allocation. Exceptions include cured basal cell carcinoma of skin and carcinoma in situ of cervix;
• Has any severe and/or uncontrolled disease;
• Has adverse events caused by previous therapy except alopecia that did not recover to ≤ grade 1;
• Has drug abuse history that unable to abstain from or mental disorders; 13. Has any severe and/or uncontrolled disease;
• Severe hypersensitivity occurs after administration of other monoclonal antibodies;
• According to the judgement of the researchers, there are other factors that may lead to the termination of the study.

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: Experimental: camrelizumab +apatinib+ Carboplatin + Etoposide; Induced stage：camrelizumab 200 mg administered intravenously (IV) on Day 1 of each 21-day cycle plus Apatinib capsules 250 mg given orally +Etoposide (100mg/m2 IV continuously on Day 1, 2 and 3）+Carboplatin（AUC 5 mg/mL/min IV on Day 1 ; maintenance stage：Camrelizumab 200 mg administered intravenously (IV) on Day 1 of each 21-day cycle plus Apatinib capsules 250 mg given orally, once daily in 21-day cycle .

Drug: camrelizumab; Camrelizumab intravenous infusion was administered at a dose of 200 mg on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4/6) and maintenance phase ,until PD.; Other Names: SHR-1210; Drug: Apatinib Mesylate; Apatinib capsules 250 mg given orally , once daily in 21-day cycle and maintenance phase,until PD.; Drug: Carboplatin; Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4/6).; Drug: Etoposide; Etoposide intravenous infusion was administered at a dose of 100 mg/m^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4/6).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least 20% increase in the sum of the longest diameter of target lesions compared to baseline, or unequivocal progression in non-target lesion(s), or the appearance of new lesion(s).	Baseline until PD or death, whichever occurs first (up to approximately 13 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) .	up to 12 months
Disease control rate (DCR)	Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD).	up to 12 months
Overall survival (OS)	Baseline until death from any cause	up to approximately 20 months
Duration of response（DOR）	For participants who demonstrate CR or PR, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first	up to 12 months
PFS rate of 6 months progression-free survival	PFS rate of progression-free survival at 6 months: the percentage of subjects who did not develop disease progression or die of any cause at 6 months after beganing.	up to 6 months

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2021
• Primary Completion (Anticipated): October 30, 2023
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: December 17, 2020
• First Submitted That Met QC Criteria: December 23, 2020
• First Posted (Actual): December 24, 2020

Study Record Updates

• Last Update Posted (Actual): December 24, 2020
• Last Update Submitted That Met QC Criteria: December 23, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Protein Kinase Inhibitors; Carboplatin; Etoposide; Apatinib
• Other Study ID Numbers: MA-SCLC-II-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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