First line, stage IV non small-cell lung cancer (NSCLC) with PD L1 expression on =50 % of tumor cells MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: KEYTRUDA
Product Name: Pemrolizumab
Pharmaceutical Form: Powder and solvent for solution for injection
Trade Name: carboplatine
Product Name: carboplatine
Pharmaceutical Form: Solution f
Sponsors
CHRU de Brest
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 years or older at diagnosis. 2. Histologically or cytologically confirmed NSCLC. 3. Stage IV NSCLC. Unresectable and non-eligible to radiotherapy stage III NSCLC are permitted. 4. For non-squamous NSCLCs and non-smoking squamous NSCLCs, no known activating mutations of EGFR and no ALK or ROS1 rearrangements. 5. PD L1 expression on =50 % of tumor cells, which will be determined locally*. 6. No prior systemic treatment for lung cancer. Patients who received adjuvant therapy are eligible if the adjuvant therapy was completed at least 12 months prior to the development of metastatic disease. 7. Palliative radiotherapy completed within one day before randomization (stereotaxic or not) is authorized. 8. At least 1 target lesion in a non-irradiated area, measurable according to RECIST v1.1. 9. An Eastern Cooperative Oncology Group (ECOG) performance status (PS) =1. 10. Life expectancy >12 weeks. 11. Patients with brain metastases at inclusion are accepted, provided that these metastases are asymptomatic, or symptomatic but treated (surgery or radiotherapy without or with corticosteroids =10 mg/day), and that they are stable on the day of inclusion. 12. No history of other malignant tumor during the previous 5 years, except for adequately treated carcinomas (in situ cervical carcinoma, basal cell carcinoma, squamous cell skin carcinoma) and low grade localized prostate cancer (Gleason =65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: 1. NSCLC with expression of PD-L1 30 Gy within 6 months of the first dose of study treatment. 6. Uncontrolled and untreated superior cava syndrome. 7. Untreated and unstable symptomatic brain metastases. 8. Leptomeningeal disease. 9. Serious concurrent conditions during the previous 6 months (severe or unstable angina pectoris, coronary or peripheral artery bypass graft of 5 years prior to the study, with no signs of relapse. 13. Psychological, family, social, or geographical factors that may interfere with the monitoring of the patient as defined by the protocol. 14. Any protected person (legal person protected by legal protection [guardianship, tutorship], person deprived of liberty, pregnant woman, breastfeeding woman, and minor). 15. Patients who participated in other concomitant studies unless observational and received study therapy or used an investigational device within 4 weeks prior to start of study treatment. 16. Known or suspected active autoimmune disease requiring an immunosuppressive therapy during the previous 2 years (corticosteroids or other immunosuppressive treatment). Any hormone replacement therapy (i.e. thyroxine [T4], insulin, or replacement systemic corticosteroids for adrenal or pituitary insufficiency, etc.) is not considered an immunosuppressive treatment and is authorized. Patients with hyperthyroidism or hypothyroidism who are stable under hormone replacement therapy may also be included. 17. Chronic use of immunosuppressive drugs and/or corticosteroids (>10 mg of prednisone daily). However, during the 14 days prior to randomization the use of the following is authorized: a. Corticosteroids as pre treatment for the administration of chemotherapy and/or for allergies or type IV hypersensitivity responses b. Daily prednisone (5 mg to 7.5 mg) as replacement therapy c. Inhaled or topical steroids. 18. Live-virus vaccination within 30 days of planned start of study treatment (seasonal flu vaccines that do not contain live virus are permitted). 19. Patients who are receiving denosumab prior to inclusion must be willing and eligible to discontinue its use and replace it with a bisphosphonate instead. 20. Previ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the superiority of the chemotherapy-pembrolizumab combination versus pembrolizumab monotherapy in the first line treatment of NSCLC patients with PD L1 expression on =50 % of tumor cells, by evaluating PFS (defined as the time from randomization until tumor progression or death from any cause) per the Response Evaluation Criteria in Solid Tumors version v1.1 (RECIST v1.1) centrally reviewed by an expert panel of clinicians;Secondary Objective: •To assess PFS, defined as the time from randomization until tumor progression or death from any cause according to RECIST v1.1, evaluated by the investigators. •To assess PFS, defined as the time from randomization until tumor progression or death from any cause according to iRECIST, and centrally reviewed by an expert panel of clinicians (iPFS). •To assess objective response to treatment by evaluating the objective response rate (ORR) and duration of response (DOR) per RECIST v1.1, and duration of treatment. •To assess OS. •To assess safety and tolerability profile of study treatments. •To assess the efficacy and toxicity according to different subgroups ;Primary end point(s): PFS, defined as the time from randomization until tumor progression or death from any cause according to RECIST v1.1, and centrally reviewed by an expert panel of clinicians.;Timepoint(s) of evaluation of this end point: Disease progression or death | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • PFS, defined as the time from randomization until tumor progression or death from any cause according to RECIST v1.1, evaluated by the investigators. • PFS, defined as the time from randomization until tumor progression or death from any cause according to iRECIST, and centrally reviewed by an expert panel of clinicians (iPFS). • ORR, defined as the proportion of patients who achieved a complete response (CR) or partial response (PR) according to RECIST v1.1 • OS, defined as the time from randomization until death from any cause. • Duration of treatment, defined as the time from the first treatment administration until the date of last treatment administration. • DOR, defined as the time from the first documented objective response (CR or PR) until disease progression or death, whichever occurs first. • Subgroup analyses: PFS, OS, ORR, DOR, duration of treatment and toxicity according to different subgroups: • Proportion (%) of patients with any AE and number of events per treatment arm for all AEs, all SAEs and all AEs of grade =3 according to the National Cancer Institute (NCI) Common terminology criteria for adverse events (CTCAE) v5.0 criteria • Proportion (%) of patients with any adverse event of special interest (AESI), defined as immune-related AE (IrAE). ;Timepoint(s) of evaluation of this end point: Disease progression or death | — |
Countries
France
Outcome results
None listed