Phase 1b NXP900 SRC family kinase inhibitor plus lorlatinib ALK/ROS1 inhibitor in ALK+ NSCLC.

This multi-center, open-label Phase 1b trial from Nuvectis Pharma tests escalating oral doses of NXP900 (a small-molecule SRC family kinase inhibitor) combined with lorlatinib (a small-molecule ALK and ROS1 tyrosine kinase inhibitor) in unresectable locally advanced or metastatic ALK-positive non-small cell lung cancer. The goal is to characterize safety/tolerability and define a dose for continued evaluation, while also measuring preliminary antitumor activity (including objective response rate, duration of response, and disease control rate). Patients must have previously received lorlatinib as a first- or second-line ALK TKI and tolerated the lorlatinib dose level being explored; one prior line of systemic chemotherapy is allowed. The scientific angle is a resistance-focused combination: layering SRC-family signaling blockade onto a best-in-class ALK inhibitor to potentially deepen or re-sensitize responses after lorlatinib exposure. Today’s care for advanced ALK+ NSCLC typically uses sequential next-generation ALK TKIs (often culminating in lorlatinib) followed by platinum-based chemotherapy ± immunotherapy depending on clinical context, so this study explores a targeted combination strategy before defaulting to broader cytotoxic therapy.