A Study of NVL-520 in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1)
Purpose
Phase 1/2, dose escalation and expansion study designed to evaluate the safety and tolerability of NVL-520, determine the recommended phase 2 dose (RP2D), and evaluate the antitumor activity in patients with advanced ROS1-positive (ROS1+) NSCLC and other advanced ROS1-positive solid tumors. Phase 1 will determine the RP2D and, if applicable, the maximum tolerated dose (MTD) of NVL-520 in patients with advanced ROS1-positive solid tumors. Phase 2 will determine the objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR) of NVL-520 at the RP2D. Secondary objectives will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and clinical benefit rate (CBR) of NVL-520 in patients with advanced ROS1-positive NSCLC and other solid tumors.
Conditions
- Locally Advanced Solid Tumor
- Metastatic Solid Tumor
Eligibility
- Eligible Ages
- Over 12 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Age ≥18 years (Cohort 2e only: Age ≥12 years and weighing>40 kg). 2. Disease Criteria: 1. Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with documented ROS1 rearrangement. 2. Phase 2: Cohorts 2a, 2b, 2c and 2d: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangement. 3. Phase 2: Cohort 2e: Histologically or cytologically confirmed locally advanced or metastatic solid tumor (other than NSCLC) with ROS1 rearrangement. 3. Prior anticancer treatment (except cohort 2a). 4. 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. 5. Adequate baseline organ function and bone marrow reserve.
Exclusion Criteria
- Patient's cancer has a known oncogenic driver alteration other than ROS1. 2. Known allergy/hypersensitivity to excipients of NVL-520. 3. Major surgery within 4 weeks of first dose of study drug. 4. Ongoing anticancer therapy. 5. Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Phase 1 dose escalation |
NVL-520 oral daily dosing |
|
|
Experimental Cohort 2a |
ROS1+ NSCLC naïve to TKI therapy and up to 1 prior chemotherapy and/or immunotherapy |
|
|
Experimental Cohort 2b |
ROS1+ NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or immunotherapy |
|
|
Experimental Cohort 2c |
ROS1+ NSCLC treated with 1 prior ROS1 TKI and 1 prior platinum-based chemotherapy with or without immunotherapy |
|
|
Experimental Cohort 2d |
ROS1+ NSCLC treated with ≥2 prior ROS1 TKIs and up to 1 prior chemotherapy and/or immunotherapy |
|
|
Experimental Cohort 2e |
ROS1+ solid tumor and progressed on any prior therapy |
|
Recruiting Locations
Washington, District of Columbia 20007
More Details
- Status
- Recruiting
- Sponsor
- Nuvalent Inc.
Detailed Description
In Phase 2, study patients will be enrolled into 5 distinct expansion cohorts: - Cohort 2a: ROS1-positive NSCLC naïve to Tyrosine Kinase Inhibitor (TKI) therapy and up to 1 prior chemotherapy and/or immunotherapy. - Cohort 2b: ROS1-positive NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or immunotherapy. - Cohort 2c: ROS1-positive NSCLC treated with 1 prior ROS1 TKI and 1 prior platinum-based chemotherapy with or without immunotherapy. - Cohort 2d: ROS1-positive NSCLC treated with ≥2 prior ROS1 TKIs and up to 1 prior chemotherapy and/or immunotherapy. - Cohort 2e: ROS1-positive solid tumor and progressed on any prior therapy.