Nuvalent, Inc. NUVL on Tuesday announced in a press release pivotal data for zidesamtinib, a novel ROS1-selective inhibitor, in TKI (tyrosine kinase inhibitor) pre-treated patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) from the global ARROS-1 Phase 1/2 trial.
Global enrollment in the study is ongoing.
As of the data cut-off date of March 21, 2025, 514 patients with ROS1-positive solid tumors received zidesamtinib at any starting dose across the Phase 1 and Phase 2 portions of the ARROS-1 clinical trial.
Of these, 432 patients with advanced ROS1-positive NSCLC were treated with zidesamtinib at the recommended Phase 2 dose (RP2D).
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Activity was observed across subsets of TKI-pretreated patients, and the durability of response was assessed. The median duration of response (mDOR) continues to mature.
In 117 ROS1 TKI pre-treated patients, the objective response rate (ORR) was 44%, with an initially estimated durability of response of 78% at the 12-month landmark and 62% at the 18-month landmark.
In the subset of 55 patients treated with one prior ROS1 TKI (crizotinib or entrectinib) ± chemotherapy, ORR was 51%, with an initial estimated durability of response of 93% at the 12- and 18-month landmarks.
In patients with measurable CNS lesions at baseline (n = 56), the intracranial objective response rate (IC-ORR) was 48%, with 20% (11/56) intracranial complete responses (CR) and two unconfirmed partial responses (PR), and IC-DOR ≥ 12 months of 71%.
In patients that had only received prior crizotinib, which has limited brain penetrance, ± chemotherapy (n = 13), the IC-ORR was 85% with 54% (7/13) intracranial CRs. There was only one CNS progression event among CNS responders.
Intracranial responses were also observed in patients previously treated with the brain-penetrant TKIs entrectinib, lorlatinib, repotrectinib or taletrectinib.
Zidesamtinib demonstrated a well-tolerated safety profile consistent with its ROS1-selective, TRK-sparing design.
In addition, Nuvalent announced progress on the advancement of clinical startup activities to support the global initiation of the ALKAZAR Phase 3 trial, which will evaluate neladalkib versus alectinib, a front-line standard of care, for patients with TKI-naïve ALK-positive NSCLC.
The company expects to begin enrollment in the early second half of 2025.
The company completed a pre-New Drug Application meeting with the U.S. Food and Drug Administration. It aligned with its plans to move forward with an NDA submission seeking an indication for the treatment of zidesamtinib in TKI-pretreated patients with locally advanced or metastatic ROS1-positive NSCLC.
The company plans to initiate a rolling NDA submission in July 2025, with completion targeted for the third quarter of 2025.
NUVL Price Action: Nuvalent stock is up 1.35% at $77.01 at publication on Tuesday
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