A Study of SHR-1210 in Combination With Pemetrexed and Carboplatin in Subjects With Non-squamous NSCLC

NCT03134872 | Completed Phase 3

• 1 other identifier: SHR-1210-III-303-NSCLC
• Study Type: interventional
• Target: 419
• Locations: 1 country
• Sites: 1

Brief Summary

SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody. This is a randomized,Phase III, multicenter ,open-label study designed to evaluate the safety and efficacy of SHR-1210 with carboplatin and pemetrexed versus carboplatin-pemetrexed in subjects who are chemotherapy naive and have Stage IIIB/IV non-squamous NSCLC. The primary hypothesis is that SHR-1210 combined with carboplatin and pemetrexed prolongs Progression Free Survival (PFS) in per RECIST 1.1 by blinded independent central review (ITT population and population was indicated by high PD-L1 expression) compared to carboplatin and pemetrexed treatment .

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Disease; Neoplasms by Site; Neoplasm, Bronchial; Carcinoma, Bronchogenic

Keywords

PD-1; PD-L1; SHR-1210; Carboplatin; Pemetrexed

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival in the intent-to-treat (ITT) population

  PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first. Patients who have not experienced disease progression or death at the time of analysis will be censored at the time of last tumor assessment.

  up to 24 months

• Progression-Free Survival in the PD-L1-selected population

  PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first. Patients who have not experienced disease progression or death at the time of analysis will be censored at the time of last tumor assessment.

  up to 24 months

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  up to 24 months

• Duration of Response Rate(DoR)

  up to 24 months

• Time To Progression (TTP)

  up to 24 months

• Disease Control Rate (DCR)

  up to 24 months

• Overall Survival

  up to 24 months

Study Arms (2)

SHR-1210+Chemotherapy

EXPERIMENTAL

Subjects receive SHR-1210 200mg and pemetrexed 500 mg/m\^2 and carboplatin AUC 5, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional SHR-1210 200mg and pemetrexed 500 mg/m\^2 every three weeks (Q3W) maintenance for the remainder of the study or until documented PD.

Biological: SHR-1210; Drug: Carboplatin; Drug: Pemetrexed

Chemotherapy

ACTIVE COMPARATOR

Subjects receive pemetrexed 500 mg/m\^2 and carboplatin Area Under the Curve (AUC) 5, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m\^2 every three weeks (Q3W) maintenance for the remainder of the study or until documented PD. If PD occurs, Subjects may be able to receive SHR-1210 Q3W for the remainder of the study or until documented PD.

Drug: Carboplatin; Drug: Pemetrexed

Interventions

SHR-1210 BIOLOGICAL

SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody.

SHR-1210+Chemotherapy

Carboplatin DRUG

Carboplatin

Chemotherapy; SHR-1210+Chemotherapy

Pemetrexed DRUG

Pemetrexed

Chemotherapy; SHR-1210+Chemotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Subjects who are chemotherapy naive and have Stage IIIB-IV non-squamous NSCLC.
• \. Subjects should not have a previously detected sensitizing EGFR mutation or ALK fusion oncogene.
• \. Fresh cutting or ≤6 months preservation specimens must be provided.
• \. No prior systemic treatment. Subjects who have received prior neo-adjuvant, adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment free interval of at least 12 months from randomization since the last chemotherapy cycle.
• \. Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria;
• \. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
• \. Have a life expectancy of at least 3 months.
• \. All baseline laboratory requirements will be assessed and should be obtained within 14 days prior to the first administration of study treatment.
• \. Female Subjects of childbearing potential must have a negative serum pregnancy test within 3 days before the first dose and must be willing to use very efficient barrier methods of contraception for the course of the study through 180 days after the last dose of study treatment.
• \. Male Subjects with a female partner(s) of child-bearing potential must be willing to use very efficient barrier methods of contraception for the course of the study through 180 days after the last dose of study treatment.
• \. Subjects has voluntarily agreed to participate by giving written informed consent/assent for the trial. The subject may also provide consent/assent for Future Biomedical Research.

You may not qualify if:

• \. Target Disease Exceptions
• Subjects with predominantly squamous cell histology NSCLC, or SCLC.
• Subjects with epidermal growth factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) translocation.
• Subjects with no measurable disease by CT or MRI per RECIST 1.1 criteria.
• Subjects with carcinomatous meningitis, or symptoms of spinal cord compression.
• Subjects with active CNS metastases are excluded.
• Subjects who can receive surgical resection or radical radiotherapy.
• Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody (including any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• \. Medical History and Concurrent Diseases
• Subjects with active, known or suspected autoimmune disease. Subjects in conditions not expected to recur in the absence of an external trigger, or not requiring systemic treatment are permitted to enroll.
• 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 doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Prior therapy with systemic immunostimulatory agents within 1 months of the first dose of trial treatment.
• Subjects are currently participating and receiving study therapy or had participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks or 5 half-value period life of the agent, before the first dose of trial treatment.
• Subjects who expected to require any other form of antineoplastic therapy while on study (including maintenance therapy with another agent for NSCLC).
• Subjects received major surgery or radiation therapy of \> 30 Gy not to chest within 4 weeks of the first dose of study treatment, or radiation therapy of \> 30 Gy to chest within 24 weeks of the first dose of study treatment, or radiation therapy of \< 30 Gy to chest within 2 weeks of the first dose of study treatment, and had not recovered from the toxicity and/or complications of the most recent prior chemotherapy to Grade 1 or less (except alopecia or fatigue).

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Tongji University, Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

Related Publications (6)

• Zhou C, Chen G, Huang Y, Zhou J, Lin L, Feng J, Wang Z, Shu Y, Shi J, Hu Y, Wang Q, Cheng Y, Wu F, Chen J, Lin X, Wang Y, Huang J, Cui J, Cao L, Liu Y, Zhang Y, Pan Y, Zhao J, Wang L, Chang J, Chen Q, Ren X, Zhang W, Fan Y, He Z, Fang J, Gu K, Dong X, Jin F, Gao H, An G, Ding C, Jiang X, Xiong J, Zhou X, Hu S, Lu P, Liu A, Guo S, Huang J, Zhu C, Zhao J, Gao B, Chen Y, Hu C, Zhang J, Zhang H, Zhao H, Wang Z, Ma X, Shi W. Camrelizumab plus carboplatin and pemetrexed as first-line therapy for advanced non-squamous non-small-cell lung cancer: 5-year outcomes of the CameL randomized phase 3 study. J Immunother Cancer. 2024 Nov 27;12(11):e009240. doi: 10.1136/jitc-2024-009240.

  PMID: 39608979 DERIVED

• Zhou C, Chen G, Huang Y, Zhou J, Lin L, Feng J, Wang Z, Shu Y, Shi J, Hu Y, Wang Q, Cheng Y, Wu F, Chen J, Lin X, Wang Y, Huang J, Cui J, Cao L, Liu Y, Zhang Y, Pan Y, Zhao J, Wang L, Chang J, Chen Q, Ren X, Zhang W, Fan Y, He Z, Fang J, Gu K, Dong X, Jin F, Gao H, An G, Ding C, Jiang X, Xiong J, Zhou X, Hu S, Lu P, Liu A, Guo S, Huang J, Zhu C, Zhao J, Gao B, Chen Y, Hu C, Zhang J, Zhang H, Zhao H, Tai Y, Ma X, Shi W; CameL Study Group. Camrelizumab Plus Carboplatin and Pemetrexed as First-Line Treatment for Advanced Nonsquamous NSCLC: Extended Follow-Up of CameL Phase 3 Trial. J Thorac Oncol. 2023 May;18(5):628-639. doi: 10.1016/j.jtho.2022.12.017. Epub 2023 Jan 13.

  PMID: 36646210 DERIVED

• Wu F, Jiang T, Chen G, Huang Y, Zhou J, Lin L, Feng J, Wang Z, Shu Y, Shi J, Hu Y, Wang Q, Cheng Y, Chen J, Lin X, Wang Y, Huang J, Cui J, Cao L, Liu Y, Zhang Y, Pan Y, Zhao J, Wang L, Chang J, Chen Q, Ren X, Zhang W, Fan Y, He Z, Fang J, Gu K, Dong X, Zhang T, Shi W, Zou J, Bai X, Ren S, Zhou C; CameL Study Group. Multiplexed imaging of tumor immune microenvironmental markers in locally advanced or metastatic non-small-cell lung cancer characterizes the features of response to PD-1 blockade plus chemotherapy. Cancer Commun (Lond). 2022 Dec;42(12):1331-1346. doi: 10.1002/cac2.12383. Epub 2022 Nov 4.

  PMID: 36331328 DERIVED

• Xie Q, Zheng H, Su N, Li Q. Camrelizumab in patients with advanced non-squamous non-small cell lung cancer: a cost-effective analysis in China. BMJ Open. 2022 Aug 5;12(8):e061592. doi: 10.1136/bmjopen-2022-061592.

  PMID: 36194670 DERIVED

• Chen T, Xie R, Zhao Q, Cai H, Yang L. Cost-Utility Analysis of Camrelizumab Plus Chemotherapy Versus Chemotherapy Alone as a First-Line Treatment for Advanced Nonsquamous Non-Small Cell Lung Cancer in China. Front Oncol. 2022 Jul 22;12:746526. doi: 10.3389/fonc.2022.746526. eCollection 2022.

  PMID: 35936702 DERIVED

• Zhou C, Chen G, Huang Y, Zhou J, Lin L, Feng J, Wang Z, Shu Y, Shi J, Hu Y, Wang Q, Cheng Y, Wu F, Chen J, Lin X, Wang Y, Huang J, Cui J, Cao L, Liu Y, Zhang Y, Pan Y, Zhao J, Wang L, Chang J, Chen Q, Ren X, Zhang W, Fan Y, He Z, Fang J, Gu K, Dong X, Zhang T, Shi W, Zou J; CameL Study Group. Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): a randomised, open-label, multicentre, phase 3 trial. Lancet Respir Med. 2021 Mar;9(3):305-314. doi: 10.1016/S2213-2600(20)30365-9. Epub 2020 Dec 18.

  PMID: 33347829 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasms by Site; Bronchial Neoplasms; Carcinoma, Bronchogenic

Interventions

camrelizumab; Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Neoplasms; Bronchial Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Wei Shi, MD

  Jiangsu HengRui Medicine Co., Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2017
• First Posted: May 1, 2017
• Study Start: May 12, 2017
• Primary Completion: July 27, 2019
• Study Completion: August 29, 2019
• Last Updated: June 9, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)