Metastatic Non-Small Cell Lung Cancer Metastatic Non-Small Cell Lung Cancer
Conditions
Interventions
It is anticipated that patients will receive at least 1 cycle of study
treatment (pralsetinib if randomized to Arm A and a platinum-containing
chemotherapy regimen from an Investigator's choice list
Sponsors
Roche Nederland B.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Participant must be >= 18 years at the time of signing Informed Consent Form • Participant has pathologically confirmed, definitively diagnosed, advanced unresectable NSCLC (i.e., Stage IIIB not eligible for definitive chemoradiotherapy) or metastatic NSCLC (i.e., Stage IV), per the Union Internationale Contre le Cancer/American Joint Committee on Cancer staging system (Amin et al. 2017) of either squamous or non-squamous histology based on the major histologic component that has not been treated with systemic anticancer therapy for metastatic disease • Participant has documented RET fusion that must meet 1 of the following 2 criteria: a. Documented RET fusion using either tissue or plasma as performed by a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalent accredited diagnostic laboratory. b. Documented RET fusion by a positive result from tumor tissue testing performed centrally by Foundation Medicine (FMI) clinical trial assay or an alternate, approved central laboratory for that region. • The participant agrees to provide adequate tumor tissue for central confirmation of RET fusion status using an NGS-based Assay. • Participant has measurable disease based on RECIST 1.1 as determined by the local site Investigator/radiology assessment. Lesions located in a previously irradiated area are considered measurable if progression has been demonstrated after irradiation • Participants has an ECOG PS of 0-1 • Participants who have a negative HIV test at screening. If HIV positive, participant should be stable on anti-retroviral therapy with a CD4 count >= 200/µL, and have an undetectable viral load. • Patient cannot have received any prior anticancer therapy for metastatic disease a. Patients can have received previous anticancer therapy (except a selective RET inhibitor) in the neoadjuvant or adjuvant setting but must have experienced an interval of at least >= 6 months from completion of therapy to recurrence b. Patients that received previous immune checkpoint inhibitors in the adjuvant or consolidation setting following chemoradiation are not allowed to receive pembrolizumab if randomized in Arm B • Participant is an appropriate candidate for and agrees to receive 1 of the Investigator choice platinum-based anticancer regimens if randomized to Arm B • For men and women of childbearing potential: must agree to remain abstinent or use a highly effective contraceptive method during treatment period for 7 and 14 days respectively after the final dose of pralsetinib. Men must refrain from donating sperm during this same period.
Exclusion criteria
Exclusion criteria: • Participant*s tumor has any additional known primary driver alterations other than RET, such as targetable mutations of EGFR, ALK, ROS1, MET, and BRAF. Investigators should discuss enrollment of participants with tumors having co-mutations • Participant previously received treatment with a selective RET inhibitor. • Participant received radiotherapy or radiosurgery to any site within 14 days before randomization or more than 30 Gy of radiotherapy to the lung in the 6 months before randomization. • Participants with a history of pneumonitis within the last 12 months • Participant with autoimmune disease that requires systemic therapy. Participants with autoimmune disease within 2 years of treatment are not eligible for the pembrolizumab-containing regimen. • Participants with a medical condition that requires immunosuppression • Participants has CNS metastases or a primary CNS tumor that is associated with progressive neurological symptoms or requires increasing doses of corticosteroids to control the CNS disease. If a participant requires corticosteroids for management of CNS disease, the dose must have been stable for the 2 weeks before C1D1 • Participant has a QT interval corrected using Fridericia's formula (QTcF) >480 msec. Patient has a history of prolonged QT syndrome or torsades de pointes. Participant has a familial history of prolonged QT syndrome. • Participant has clinically significant, uncontrolled, cardiovascular disease including congestive heart failure Grade III or IV according to the New York Heart Association (NYHA) classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension, or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation • Participant requires treatment with a prohibited medication or herbal remedy that cannot be discontinued at least 2 weeks before the start of study drug administration. Pralsetinib may be started within 14 days of stopping a prohibited medication if considered by the Investigator to be safe and within the best interest of the patient, with prior Sponsor approval. • Participant received treatment with hematopoietic growth factor support within 14 days of the first dose of study drug. • Patient has had a major surgical procedure within 14 days of the first dose of study drug or is planned to have such procedure during the study period • Participant has a history of another primary malignancy that has been diagnosed or required therapy within the past 3 years before randomization. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, curatively treated localized thyroid cancer, and completely resected carcinoma in situ of any site. • Participant with a serious infection requiring systemic antibiotic therapy within 7 days prior to initiation of study treatment, or any active infection that, in the opinion of the investigator, could impact patient's safety • Participant has an active, uncontrolled infection • Participant is pregnant, • Participant is breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary • PFS, defined as the time from randomization date to the first of documented progressive disease (PD), as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or death due to any cause, whichever occurs first | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Objective response rate (ORR) defined as the proportion of participants with a CR or a PR on two consecutive occasions = 4 weeks apart, as assessed by BICR according to RECIST v1.1 2. Overall survival (OS) , defined as the time to randomization date to death due to any cause. 3. Incidence and severity of adverse events, with severity, as determined according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 5.0 4. Change from baseline in ECOG performance status 5. Change from baseline in targeted vital signs 6. Change from baseline in targeted clinical laboratory test results 7. Duration of response (DOR), defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as assessed by BICR according to RECIST v1.1 8. Disease control rate (DCR), defined as the proportion of participants who experience a best response of CR, or PR, or SD, as assessed by BICR according to RECIST v1.1 9. Clinical benefit rate (CBR), defined as the proportion of participants who experience a best response of SD with a minimum duration of 6 months, a CR, or a PR, as assessed by BICR according to RECIST v1.1 10. Change from baseline in PROs of health-related quality-of-life, lung cancer-related symptoms, and their impact on functioning. 11. Time to confirmed deterioration of participant-reported physical functioning and Health | — |
Countries
Netherlands
Outcome results
None listed