Thoracic Cancer S1900B

A Phase II Study of LOXO-292 in Patients With RET Fusion-Positive Stage IV or Recurrent Non-Small Cell Lung Cancer (LUNG-MAP Sub-Study)

This phase II LUNG-MAP treatment trial studies how well selpercatinib works in treating patients with RET fusion-positive non-small cell lung cancer that is stage IV or has come back (recurrent). Selpercatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Eligibility Criteria:

• Patients must have been assigned to S1900B based on biomarker analysis of tissue and/or blood and determined to have RET fusion-positive NSCLC as defined here:

• Patients must have RET fusion-positive NSCLC as determined by the Foundation Medicine (FMI) tissue-assay, other tumor-based assays such as next-generation sequencing (NGS), polymerase chain reaction (PCR), or follicular in situ hybridization (FISH), or by cfDNA blood assay. Patients with RET fusions detected by immunohistochemistry (IHC) alone are not eligible. The testing must be done within a laboratory with Clinical Laboratory Improvement Act (CLIA), International Organization for Standardization (ISO/International Electrotechnical Commission (IEC), College of American Pathologists (CAP), or similar certification. Presence of RET fusions detected on tests performed outside of LUNGMAP must have been confirmed by the study biomarker review panel

• For patients whose prior therapy was for stage IV or recurrent disease, the patient must have received at least one line of a platinum-based chemotherapy regimen. For patients whose prior systemic therapy was for stage I-III disease only (i.e. patient has not received any treatment for stage IV or recurrent disease), disease progression on platinum-based chemotherapy must have occurred within one year from the last date that the patient received that therapy. Prior anti-PD-1/PD-L1 therapy, alone or in combination (e.g. nivolumab, pembrolizumab, or durvalumab) is allowed

• Patients must be negative for all additional validated oncogenic drivers that could cause resistance to LOXO-292 treatment. This includes EGFR sensitizing mutations, EGFR T790M, ALK gene fusion, ROS1 gene fusion, KRAS activating mutation, BRAF V600E mutation and MET exon 14 skipping mutation or high-level amplification and expression

• • Note: EGFR, ALK, ROS, KRAS, and BRAF testing is performed as part of the LUNGMAP screening/pre-screening FoundationOne test. If prior data is not available, results from the FMI testing must be obtained prior to sub-study registration

Available at: Hartford HealthCare, Hospital of Central Connecticut, Midstate Medical Center, William Backus Hospital