Overview
This is an international, randomized, open-label, Phase 3 study designed to evaluate whether the potent and selective RET inhibitor, pralsetinib, improves outcome when compared to a platinum chemotherapy-based regimen chosen by the Investigator from a list of standard of care treatments, as measured primarily by progression free survival (PFS), for patients with RET fusion-positive metastatic NSCLC who have not previously received systemic anticancer therapy for metastatic disease. Patients who have centrally confirmed progressive disease on the control arm have the option to crossover to pralsetinib.
Eligibility
Main inclusion criteria:
- Patient is 18 years of age
- Patient has pathologically confirmed, definitively diagnosed, advanced (not able to be treated with surgery or radiotherapy) or metastatic NSCLC and has not been treated with systemic anticancer therapy for metastatic disease.
- Patient must have a documented RET-fusion
- Patient has measurable disease based on RECIST 1.1 as determined by the local site Investigator/radiology assessment.
- Patient has an ECOG PS of 0-1.
- Patient should not have received any prior anticancer therapy for metastatic disease.
- 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.
- Patients that received previous immune checkpoint inhibitors in the adjuvant or consolidation following chemoradiation are not allowed to receive pembrolizumab if randomized in Arm B
- Patient is an appropriate candidate for and agrees to receive 1 of the Investigator choice platinum-based chemotherapy regimens if randomized to Arm B.
- Patient provides signed informed consent to participate in the study.
Main exclusion criteria:
- Patient'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 with Sponsor designee regarding co-mutations.
- Patient previously received treatment with a selective RET inhibitor.
- Patient 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.
- Patient has a presence of Grade 2 or worse interstitial lung disease or interstitial pneumonitis, including radiation pneumonitis within 28 days before randomization.
- Patient 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 patient requires corticosteroids for management of CNS disease, the dose must have been stable for the 2 weeks before Cycle 1 Day 1.