Phase II Single-arm Clinical Study of Camrelizumab Combined With Apatinib Mesylate and Standard Chemotherapy (Pemetrixed +Carboplatin) in Patients With Tyrosine Kinase Inhibitor Failure in ALK-positive Advanced NSCLC

The First Affiliated Hospital of Xiamen University0 sites59 target enrollmentJuly 2020

ConditionsLung Neoplasms

InterventionsCamrelizumab Apatinib Pemetrixed Carboplatin

DrugsCamrelizumab Apatinib Pemetrixed Carboplatin

Overview

Phase: Phase 2
Intervention: Camrelizumab
Conditions: Lung Neoplasms
Sponsor: The First Affiliated Hospital of Xiamen University
Enrollment: 59
Primary Endpoint: Objective response rate (ORR)
Status: Not yet recruiting
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

This study is a phase II single-arm clinical study.The purpose of this study was to evaluate the efficacy and safety of carrelizumab combined with apatinib mesylate and standard chemotherapy (pemetrexed plus carboplatin) in patients with advanced non-squamous and non-small cell lung cancer who have failed tyrosine kinase inhibitor therapy and are ALK-positive.

Registry

clinicaltrials.gov

Start Date

July 2020

End Date

January 2025

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

The First Affiliated Hospital of Xiamen University

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age 18 - 75 year，male or female；
•Subjects with histologically or cytologically confirmed advanced non-squamous non-small cell lung cancer, imaging stage IIIb\~IV；
•ALK fusion gene is positive and meets the following conditions:
•First-line treatment failure after previous second-generation ALK-TKI (including but not limited to Aletinib, Ceritinib, Brigatinib, and x-396);
•Previous first-generation AlK-TKI (crizotinib) and second-generation ALK-TKI (including but not limited to Aletinib, Ceritinib, Brigatinib, and x-396) failed.
•Patients with at least one evaluable or measurable lesions as per RECIST version 1.1；
•Patients who have not previously received systematic chemotherapy for advanced lung cancer .Can also be enrolled if you have previously received Neoadjuvant or adjuvant therapy；
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1；
•Survival expectation ≥ 3 months;
•Women of childbearing age must have a serum pregnancy study within 2 weeks prior to the first dose and the results are negative. Female subjects of childbearing age and partners who are women of childbearing age must be contraceptive during the study period and within 180 days after the last administration of the study drug;

Exclusion Criteria

•Tumor histology or cytology pathology confirmed that the components of small cell lung cancer or squamous cell carcinoma were more than 10%；
•Previously received any T cell costimulation or immunological checkpoint treatment, including but not limited to CTLA-4 inhibitors, PD-1 inhibitors, PD-L1/2 inhibitors or other T cell-targeting drugs；
•An active autoimmune disease requiring systemic treatment (such as the use of disease-alleviating drugs, corticosteroids or immunosuppressants) occurred within 2 years prior to the first administration.Alternative therapies (such as thyroxine, insulin or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic;
•Interstitial lung disease, drug-induced pneumonia, radiation pneumonitis requiring steroid therapy or active pneumonia with clinical symptoms or severe pulmonary dysfunction；
•Previous or current history of cancer other than NSCLC, except for non-melanoma skin cancer, in-situ cervical cancer or other cancers that have received curable treatment and have shown no signs of recurrence for at least 5 years；
•Has not fully recovered from toxicity and/or complications from any intervention prior to initiation of treatment (i.e., ≤ grade 1 or level required at baseline, excluding fatigue or hair loss);
•Have a tendency to hereditary bleeding or coagulopathy. Clinically significant bleeding symptoms or clear bleeding tendency within 3 months prior to enrollment, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood++ and above；
•Patients with clear or suspected brain metastases. Patients with a history of brain metastases （must be completed and patients who are no longer in need of corticosteroid therapy） can be enrolled; for patients with asymptomatic, lesions ≤ 3 and single less than 10 mm, who is determined by the investigator whether or not to enroll ;
•There are clinical symptoms or diseases of the heart that are not well controlled, such as: (1) heart failure of NYHA class 2 or higher (2) unstable angina (3) myocardial infarction within 24 weeks (4) clinical need for treatment or Interventional supraventricular or ventricular arrhythmia；
•Uncontrolled hypertension after treatment (systolic blood pressure \> 140 mmHg and/or diastolic blood pressure \> 90mmHg), with a history of hypertensive crisis or hypertensive encephalopathy;Uncontrolled hyperglycemia after treatment (fasting glucose \>8.9mmol/L);

Arms & Interventions

Camrelizumab +apatinib mesylate+Pemetrixed + Carboplatin

Camrelizumab combined with apatinib mesylate,Pemetrixed and Carboplatin in the treatment（4-6 cycle）of effective (CR, PR, SD) patients continued to be treated with Camrelizumab combined with apadine mesylate until PD, toxicity intolerance, and other reasons that the researcher thinks need to stop the research treatment.

Intervention: Camrelizumab

Camrelizumab +apatinib mesylate+Pemetrixed + Carboplatin

Intervention: Apatinib

Camrelizumab +apatinib mesylate+Pemetrixed + Carboplatin

Intervention: Pemetrixed

Camrelizumab +apatinib mesylate+Pemetrixed + Carboplatin

Intervention: Carboplatin

Outcomes

Primary Outcomes

Objective response rate (ORR)

Time Frame: up to approximately 1 year

ORR, determined using RECIST v1.1, defined as best overall response (CR or PR) across all assessment time points during the period from enrolment to termination of trial treatment.