A Study of NVL-520 in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1)

Nuvalent

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Locally Advanced Solid Tumor; Metastatic Solid Tumor

Treatments: Drug: NVL-520

Study type: Interventional

Funder types: Industry

Identifiers

NCT05118789

NVL-520-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 359 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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

1. 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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359 participants in 6 patient groups

Phase 1 dose escalation

Experimental group

Description:

NVL-520 oral daily dosing

Treatment:

Drug: NVL-520

Cohort 2a

Experimental group

Description:

ROS1+ NSCLC naïve to TKI therapy and up to 1 prior chemotherapy and/or immunotherapy

Treatment:

Drug: NVL-520

Cohort 2b

Experimental group

Description:

ROS1+ NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or immunotherapy

Treatment:

Drug: NVL-520

Cohort 2c

Experimental group

Description:

ROS1+ NSCLC treated with 1 prior ROS1 TKI and 1 prior platinum-based chemotherapy with or without immunotherapy

Treatment:

Drug: NVL-520

Cohort 2d

Experimental group

Description:

ROS1+ NSCLC treated with ≥2 prior ROS1 TKIs and up to 1 prior chemotherapy and/or immunotherapy

Treatment:

Drug: NVL-520

Cohort 2e

Experimental group

Description:

ROS1+ solid tumor and progressed on any prior therapy

Treatment:

Drug: NVL-520