Forty percent objective response rate across ten distinct solid tumor histologies — in a 15-patient cohort with no discontinuations due to treatment-related adverse events — is a genuinely unusual early signal for a basket trial population this heavily pre-treated. That number comes from ARROS-1, Nuvalent’s Phase 1/2 study of zidesamtinib in ROS1-positive solid tumors outside NSCLC, where 60% of patients were refractory to standard-of-care chemotherapy and 40% had already failed a prior ROS1 TKI. The durability cases are the real story: a patient with inflammatory myofibroblastic tumor on treatment for approximately 42 months, and two others — metastatic colorectal cancer and cholangiocarcinoma — with ongoing partial responses past the one-year mark. These are diseases where ROS1 fusion prevalence is low and molecularly-matched options are essentially nonexistent.
The design logic matters here. Zidesamtinib’s ROS1-selective, TRK-sparing profile is doing real work — one dose reduction across 15 patients is a tolerability signal that will matter enormously as Nuvalent tries to enroll the Phase 2 expansion in tumor types where oncologists rarely think to order ROS1 testing. A clean safety readout at this stage reduces the friction of physician adoption in unfamiliar settings. The Phase 2 portion is enrolling both TKI-naïve and TKI pre-treated adult and adolescent patients, which means the regulatory path being constructed here is deliberately broad across age and prior-treatment strata.
Simultaneously, the ALKOVE-1 pivotal data for neladalkib in ALK-positive NSCLC — already the foundation of an NDA filed in April 2026 — will get an oral presentation on May 29. The oral slot matters. ASCO’s lung cancer metastatic session carries weight with the community that will prescribe against alectinib, lorlatinib, and brigatinib. The Phase 3 ALKAZAR trial comparing neladalkib to alectinib in TKI-naïve patients is Nuvalent’s shot at the front line, but the NDA for pre-treated patients is the nearer commercial event — and the ASCO presentation is effectively the last major data moment before FDA review unfolds.
The single marker to track from ASCO is the intracranial response rate for neladalkib in ALKOVE-1. CNS activity is the functional discriminator in the late-line ALK space, and how that number compares to lorlatinib’s benchmark will determine how aggressively oncologists reach for neladalkib before ALKAZAR reads out.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
