Efficacy and Safety of Toripalimab (JS001) Combined With Pemetrexed and Anlotinib for Patients With T790M Positive Non-Small Cell Lung Cancer After Osimertinib Resistance：a Phase II,Muti-center, Single Arm Study

Guangzhou Institute of Respiratory Disease1 site in 1 country60 target enrollmentApril 1, 2020

ConditionsIIIb/IV NSCLC With T790M Positive Mutations Failed to Osimertinib Therapy

InterventionsToripalimab + Pemetrexed + Anlotinib

DrugsToripalimab + Pemetrexed + Anlotinib

Overview

Phase: Phase 2
Intervention: Toripalimab + Pemetrexed + Anlotinib
Conditions: IIIb/IV NSCLC With T790M Positive Mutations Failed to Osimertinib Therapy
Sponsor: Guangzhou Institute of Respiratory Disease
Enrollment: 60
Locations: 1
Primary Endpoint: Overall response rate （ORR）
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open-label, single-arm, multi-center, phase II exploratory study that evaluates the efficacy and safety of Toripalimab injection (JS001) combined with Pemetrexed and Anlotinib as a second-line treatment for patients with T790M positive Non-Small Cell Lung Cancer (IIIb / IV ) after Osimertinib resistance.

Registry

clinicaltrials.gov

Start Date

April 1, 2020

End Date

April 1, 2022

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Guangzhou Institute of Respiratory Disease

Responsible Party

Principal Investigator

Zhou Chengzhi

Chief Physician

Guangzhou Institute of Respiratory Disease

Eligibility Criteria

Inclusion Criteria

•Fully understand this study and voluntarily sign the informed consent form (ICF);
•Histologically and/or cytologically confirmed Stage IIIb / IV NSCLC (according to the seventh edition of AJCC); patients with T790M-positive mutations who were resistant to Osimertinib treatment;
•At least one measurable lesion (according to RECIST 1.1); Note: Lesions that have previously received radiotherapy cannot be regarded as target lesions, unless the lesions clearly progress after radiotherapy;
•Agree to provide formalin-fixed tumor specimens or biopsy specimens after the subject is diagnosed with metastatic cancer, at least 15 sections; if the recent biopsy is not feasible, allow to receive biopsy specimens before adjuvant/neo-adjuvant chemotherapy (archived specimens);
•ECOG PS 0-2
•Life expectancy ≥3 months.
•The laboratory examination results within 7 days before enrollment must meet the following standards:
•Neutrophils ≥1.5 × 109 / L;
•Platelets ≥100 × 109 / L;
•Hemoglobin ≥90g / L (no infusion of concentrated red blood cells within 4 weeks);

Exclusion Criteria

•Incorporate other driver gene mutations with known drug treatments, including but not limited to: ALK gene rearrangement, ROS1 mutation, BRAF600E mutation, etc .;
•Received systemic chemotherapy for advanced NSCLC within 4 weeks before enrollment;
•Have received EGFR-TKI treatment within 2 weeks before enrollment;
•Received radiotherapy within 4 weeks or radiopharmaceutical treatment within 8 weeks before enrollment, except for local palliative radiotherapy for bone metastases;
•Uncontrollable or symptomatic hypercalcemia (\> 1.5mmol / L ionized calcium or calcium\> 12 mg / dL or corrected serum calcium\> ULN);
•Have undergone major surgery or have not completely recovered from the previous operation within 4 weeks before enrollment ;
•The toxicity of previous antitumor treatment has not recovered to CTCAE 0-1, except for hair loss；
•Active or untreated CNS metastases detected by CT or MRI before screening and imaging evaluation: If a new asymptomatic CNS metastases is detected during the screening period , it must undergo radiation therapy and / or surgery . After treatment, if met all other criteria, no additional brain scan is required . Patients who have previously received brain or meningeal metastasis treatment and maintained clinical stability for at least 2 weeks, stopped systemic hormonal therapy (\> 10 mg / day of prednisone or other equivalent hormones) for more than 2 weeks can be included;
•Spinal cord compression that has not undergone radical surgery and / or radiation therapy, or previously diagnosed spinal cord compression with no clinical evidence showing that the disease is stable for ≥ 4 weeks before enrollment
•Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once a month or more frequently);

Arms & Interventions

Toripalimab + Pemetrexed + Anlotinib

Intervention: Toripalimab + Pemetrexed + Anlotinib

Outcomes

Primary Outcomes

Overall response rate （ORR）

Time Frame: two years

Defined as percentage of participants achieving complete response (CR) and partial response (PR) assessed by the Independent Review Committee (IRC) according to the RECIST 1.1