A Study of NVL-655 in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)

Sponsor: Nuvalent Inc.

Sponsor score: 60
Inactive

ClinicalTrials ID:NCT05384626

Patient View

This Phase 1/2 study evaluates NVL-655, an oral tablet, in patients with advanced ALK+ NSCLC and other solid tumors. It includes dose escalation and expansion to assess safety, tolerability, and antitumor activity. Eligible participants must have ALK rearrangement/mutation, measurable disease, and adequate organ function. Exclusions include other oncogenic drivers and recent major surgery.

Patient Parameters

Program Overview

Phase 1/2, dose escalation and expansion study designed to evaluate the safety and tolerability of NVL-655, determine the recommended phase 2 dose (RP2D), and evaluate the antitumor activity in patients with advanced ALK- positive (ALK+) NSCLC and other solid tumors.

Phase 1 will evaluate the overall safety and tolerability of NVL-655 and will determine the RP2D and, if applicable, the MTD of NVL-655 in patients with advanced ALK+ solid tumors.

Phase 2 will determine the objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR) of NVL-655 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-655 in patients with advanced ALK-positive NSCLC and other solid tumors.

Description

In Phase 2, study patients will be enrolled into 6 distinct cohorts:

  • Cohort 2a: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received 1 prior 2nd-generation ALK TKI (ceritinib, alectinib, or brigatinib). Up to 2 prior lines of chemotherapy and/or immunotherapy are allowed.
  • Cohort 2b: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received 2-3 prior ALK TKIs (crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib). Up to 2 prior lines of chemotherapy and/or immunotherapy are allowed.
  • Cohort 2c: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received lorlatinib as the only prior ALK TKI therapy. Up to one prior line of chemotherapy and/or immunotherapy received prior to lorlatinib is allowed.
  • Cohort 2d: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who are naïve to ALK TKI therapy. Up to one prior line of chemotherapy and/or immunotherapy is allowed.
  • Cohort 2e: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts.
  • Cohort 2f: Patients with other solid tumors harboring an ALK rearrangement or activating ALK mutation, who have received ≥1 prior systemic anticancer therapy, or for whom no satisfactory standard therapy exists.

Eligibility Criteria

Inclusion Criteria

  1. Age ≥18 years, Phase 2 Cohort 2f only: Age ≥12 years and weighing >40 kg.

  2. Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation.

  3. Phase 2

    1. Phase 2 Cohorts except 2f: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with a documented ALK rearrangement
    2. Phase 2 Cohort 2f: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation detected by certified assay.

  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 organ function and bone marrow reserve

Exclusion Criteria

  1. Patient's cancer has a known oncogenic driver alteration other than ALK.
  2. Known allergy/hypersensitivity to excipients of NVL-655.
  3. Major surgery within 4 weeks of the study entry
  4. Ongoing or anticancer therapy
  5. Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.

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