A Study of NVL-655 in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Purpose
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.
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, 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
- 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.
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-655 oral daily dosing |
|
|
Experimental 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. |
|
|
Experimental 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. |
|
|
Experimental 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. |
|
|
Experimental 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. |
|
|
Experimental Cohort 2e |
Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts. |
|
|
Experimental 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. |
|
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 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.