A Phase I/II Study of the Highly Selective ROS1 Inhibitor NVL-520 in Patients With Advanced NSCLC and Other Solid Tumors (ARROS-1)
Considering participating in a START clinical trial?
Study Summary
To evaluate NUV-520 in ROS1-positive non-small cell lung cancer
To study NVL-520, an inhibitor of ROS1 protein, in patients with advanced Non-Small Cell Lung Cancer and other solid tumors that are ROS1-positive
To evaluate the safety and tolerability of NVL-520, determine the recommended phase 2 dose (RP2D), characterization of the pharmacokinetic profile, and evaluate the antitumor activity in patients with advanced ROS1-positive (ROS1+) NSCLC and other advanced ROS1-positive solid tumors
To evaluate the safety and activity of NVL-520 in patients with solid tumors harboring ROS1 fusions, including those with ROS1 resistance mutations and CNS metastases
The Phase 1 portion of the trial was designed to evaluate the overall safety and tolerability of zidesamtinib, with additional objectives including determination of the recommended Phase 2 dose, characterization of the pharmacokinetic profile, and evaluation of preliminary anti-tumor activity. The ongoing global, single arm, open label Phase 2 portion is designed with registrational intent for TKI-naïve and TKI pre-treated patients with ROS1-positive NSCLC.
To present the pivotal data for TKI pre-treated ROS1+ NSCLC (including post-repotrectinib and -taletrectinib) and the first report of preliminary data for TKI-naïve ROS1+ NSCLC.
The pivotal efficacy analysis included TKI pre-treated patients with measurable disease by BICR who started zidesamtinib at 100 mg QD by 31 May 2024. A preliminary analysis evaluated TKI-naïve patients treated by 31 Aug 2024.
The Phase 1 portion of the trial was designed to evaluate the overall safety and tolerability of zidesamtinib, with additional objectives including determination of the recommended Phase 2 dose (RP2D), characterization of the pharmacokinetic profile, and evaluation of preliminary anti-tumor activity.
- Age ≥18 years (Cohort 2e only: Age ≥12 years and weighing>40 kg).
- Disease Criteria:
- Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with documented ROS1 rearrangement.
- Phase 2: Cohorts 2a, 2b, 2c and 2d: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangement.
- Phase 2: Cohort 2e: Histologically or cytologically confirmed locally advanced or metastatic solid tumor (other than NSCLC) with ROS1 rearrangement.
- Prior anticancer treatment (except cohort 2a).
- Phase 1: Must have evaluable disease (target or nontarget) according to RECIST 1.1. Phase 2: Must have measurable disease according to RECIST 1.1.
- Adequate baseline organ function and bone marrow reserve.
- Phase 1 includes adult patients with any solid tumor type harboring a ROS1 gene fusion (by local testing), with evaluable disease, who have received > or = 1 prior ROS1 TKI. Prior platinum-based chemotherapies and/or immunotherapies, as well as stable CNS disease, are allowed.
- Patient’s cancer has a known primary driver alteration other than ROS1.
- Known allergy/hypersensitivity to excipients of NVL-520.
- Major surgery within 4 weeks of study entry.
- Ongoing anticancer therapy
- Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study
- Exclusion Criterion #11. 5. Adequate underlying organ function and bone marrow reserve Must have evaluable disease (objective or not) per RECIST 1.1. (Eisenhauer et al, 2009; Appendix 3). Stage 2: Must have measurable disease, defined as > or = 1 radiologically measurable target lesion per RECIST 1.1. Note: Patients with CNS-only disease are eligible as long as the disease is evaluable (Phase 1) or measurable (Phase 2) and does not meet Exclusion Criterion #11. 5. Adequate underlying organ function and bone marrow reserve Must have evaluable disease (objective or not) per RECIST 1.1. (Eisenhauer et al, 2009; Appendix 3). Stage 2: Must have measurable disease, defined as > or = 1 radiologically measurable target lesion per RECIST 1.1. Note: Patients with CNS-only disease are eligible as long as the disease is evaluable (Phase 1) or measurable (Phase 2) and does not meet Exclusion Criterion #11. 5. Adequate underlying organ function and bone marrow reserve patients with CNS-only disease are eligible as long as the disease is evaluable (Phase 1) or measurable (Phase 2) and does not meet Exclusion Criterion #11. 5. Adequate underlying organ function and bone marrow reserve patients with CNS-only disease are eligible as long as the disease is evaluable (Phase 1) or measurable (Phase 2) and does not meet Exclusion Criterion #11. 5. Adequate underlying organ function and bone marrow reserve
Clinical Study Information for Healthcare Providers
By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.