A Phase II Study of Pembrolizumab Plus Platinum and Pemetrexed as First Line Therapy in Advanced Non-squamous Non-small Cell Lung Cancer Patients With EGFR Exon 21 Point Mutation and Programmed Cell Death Ligand 1 Expression
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab, pemetrexed, platinum
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- Peking Union Medical College Hospital
- Enrollment
- 37
- Locations
- 1
- Primary Endpoint
- progression free survival 1 (PFS1)
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
A phase II, single-arm, open-label study evaluating efficacy, safety and feasibility of combined chemotherapy and pembrolizumab as first line therapy and Osimertinib as second line therapy in advanced non squamous NSCLC adult patients with epidermal growth factor receptor (EGFR) exon 21 point mutation and programmed cell death receptor ligand 1 (PD-L1) positive.
Detailed Description
Four cycles of platinum and pemetrexed in combination with pembrolizumab will be administered as first line therapy and up to 31 cycles pemetrexed and pembrolizumab maintenance therapy every 3 weeks. Osimertinib will be the sequential treatment strategy at progression.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female, ≥18 years old
- •Primary non-squamous non-small cell lung cancer(NSCLC) with stage IV (AJCC stage,8th Edition) confirmed by cytology or histology
- •Patients who have not used any anti-tumor therapy drugs such as targeted drugs, chemotherapy or immunotherapy and patients after surgery are acceptable
- •EGFR exon 21 point mutation confirmed by gene test of tissue or blood and PD-L1 (22C3) TPS≥1% confirmed by immunohistochemical method
- •At least one evaluable focus judged according to RECIST 1.1 standard
- •Eastern Cooperative Oncology Group performance score (PS) 0 or 1
- •Adequate blood function: absolute neutrophil count (ANC) ≥ 2 × 109 / L, platelet count ≥ 100 × 109 / L and hemoglobin 110 ≥ 9 g / dl. Adequate renal function: serum creatinine ≤ upper limit of normal value. Adequate liver function: total bilirubin ≤ upper limit of normal value(ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ upper limit of normal value (ULN); alkaline phosphatase ≤ upper limit of normal value (ULN)
- •Life expectancy is not less than 6 months
- •Male participants: Male participants must take effective contraception and do not donate sperm during the study and 180 days at least after the last dose
- •Female participants can not be pregnant, breastfeeding, and meet at least one of the following conditions:
Exclusion Criteria
- •patients who have active autoimmune disease which needs systemic treatment like disease relievers, corticosteroids, or immunosuppressants) in the last 2 years e. Alternative therapies ( such as thyroxine, insulin, and physiologic corticosteroid replacement therapy of adrenal or pituitary function insufficiency) are permitted)
- •History of pneumonia (non-infectious)/interstitial lung disease which require s steroid treatment or a current pneumonia/interstitial lung disease
- •Previously diagnosed immunodeficiency diseases, such as immunoglobulin deficiency, aplastic anemia
- •Known history of human immunodeficiency virus (HIV) infection
- •Patients who have hepatitis B (defined as hepatitis B virus (HBV) DNA \> 1000 copy number) and hepatitis C virus (HCV) (defined as HCV RNA (+) infection
- •Known history of active tuberculosis infection
- •Patients who received live or attenuated vaccine within 30 days prior to the first study intervention and inactivated vaccines are allowed.
- •Patients who have other known malignancies within the past 1 year and needs treatment. Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that has undergone potentially curative treatment, and bladder carcinoma in situ are not included.
- •Patients who have symptomatic central nervous system metastases and/or meningitis
- •History of hypersensitivity ( ≥ Level 3) to pembrolizumab/pemetrexed/platinum/osimertinib and/or any of its excipients
Arms & Interventions
experimental group
Four cycles of platinum and pemetrexed in combination with pembrolizumab will be administered as first line therapy and up to 31 cycles pemetrexed and pembrolizumab maintenance therapy every 3 weeks. Osimertinib will be the sequential treatment strategy at progression until resistance develops.
Intervention: Pembrolizumab, pemetrexed, platinum
experimental group
Four cycles of platinum and pemetrexed in combination with pembrolizumab will be administered as first line therapy and up to 31 cycles pemetrexed and pembrolizumab maintenance therapy every 3 weeks. Osimertinib will be the sequential treatment strategy at progression until resistance develops.
Intervention: Osimertinib
Outcomes
Primary Outcomes
progression free survival 1 (PFS1)
Time Frame: up to 8 weeks
the time length from enrollment to any of the following events: disease progression with first line therapy or death from any cause. Disease progression will be assessed according to RECIST 1.1
Secondary Outcomes
- progression free survival 2 (PFS2)(up to 8weeks)
- Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0(up to 8 weeks)
- objective response rate (ORR)(up to 8 weeks)
- Life quality score(up to 8 weeks)