Phase 1/2 larotrectinib plus pembrolizumab tests TRK inhibition after checkpoint failure in lung adenocarcinoma and melanoma

MD Anderson Cancer Center is running a single-center, open-label Phase 1/2 study of larotrectinib plus pembrolizumab in advanced or metastatic lung adenocarcinoma or melanoma that progressed after checkpoint-inhibitor monotherapy. Larotrectinib inhibits TRKA, TRKB, and TRKC, while pembrolizumab blocks PD-1. Treatment is given in repeated outpatient cycles, with an initial safety and dose-selection component followed by assessment of preliminary antitumor activity.

The study includes both lung adenocarcinoma and melanoma and does not require an NTRK fusion, distinguishing its biological question from larotrectinib’s established fusion-selected use. The combination tests whether TRK inhibition can alter response to renewed PD-1 blockade, but benefit beyond classic NTRK-fusion biology is unproven. Subsequent treatment choices differ markedly between melanoma and lung adenocarcinoma and depend on prior chemotherapy, molecular drivers, and available approved therapies.