Phase 2a TUB-040 NaPi2b-targeted topoisomerase 1 inhibitor ADC in nonsquamous NSCLC

Tubulis GmbH is running a randomized, open-label Phase 2a dose-optimization study of TUB-040, a NaPi2b (SLC34A2)–directed antibody-drug conjugate that delivers the topoisomerase 1 inhibitor payload exatecan into NaPi2b-expressing tumor cells. Participants with relapsed/refractory unresectable or metastatic nonsquamous NSCLC receive IV TUB-040 on Day 1 of each cycle and continue until progression or unacceptable toxicity, with two dose levels compared to define safety/tolerability, pharmacokinetics, preliminary antitumor activity, and the recommended Phase 2 dose. The core scientific angle is target-enabled delivery of a potent Topo1 payload in lung adenocarcinoma biology where NaPi2b is commonly expressed, aiming to widen the therapeutic window versus non-targeted chemotherapy. For this population today, care is sequential systemic therapy: platinum doublet chemo with or without immunotherapy in earlier lines (plus targeted therapy when an actionable driver is present), then later-line options such as docetaxel ± ramucirumab and approved ADCs depending on prior exposure and biomarkers—this trial tests whether a NaPi2b ADC can become a new post-progression option.