Recruiting

Phase 1

Phase 2

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

Sponsor:

Nuvalent Inc.

Code:

NCT05384626

Conditions

Locally Advanced Solid Tumor

Metastatic Solid Tumor

Eligibility Criteria

Sex: All

Age: 12+

Healthy Volunteers: Not accepted

Interventions

Neladalkib (NVL-655)

Midazolam

Repaglinide

Itraconazole

Study Details

Brief summary:

Phase 1/2, dose escalation and expansion study designed to evaluate the safety and tolerability of neladalkib (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 neladalkib and will determine the RP2D and, if applicable, the maximum tolerated dose (MTD) of neladalkib 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 neladalkib 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 neladalkib in patients with advanced ALK-positive NSCLC and other solid tumors.

A drug-drug interaction (DDI) sub-study will determine the effect of neladalkib on the pharmacokinetics of midazolam and repaglinide, as well as the effect of itraconazole on the pharmacokinetics of neladalkib, in patients with advanced ALK-positive NSCLC

Conditions

Locally Advanced Solid Tumor

Metastatic Solid Tumor

Study ID

NCT05384626

Start date

Jun 9, 2022

Status verified date

May, 2026

Completion date

Jan, 2028

Anticipated

Primary completion date

Dec, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 12+

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. Age ≥18 years, Phase 2 Cohort 2f only: Age ≥12 years and weighing >40 kg. DDI sub-study Cohorts G and H only: age 18-60 years, inclusive
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. DDI sub-study cohorts: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with a documented ALK rearrangement
5. DDI sub-study cohorts: Must have previously received ≥1 ALK TKI; no prior investigational agents targeting ALK; any number of prior chemotherapy and/or immunotherapy
6. 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
7. 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.

Study Design

Enrollment

840 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase 1 dose escalation

Neladalkib (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.

experimental: Cohort G (DDI sub-study)

Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI

experimental: Cohort H (DDI sub-study)

Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI

Interventions

Neladalkib (NVL-655)

Oral Tablet of Neladalkib (NVL-655)

Midazolam

Oral Solution of Midazolam

Repaglinide

Oral Tablet of Repaglinide

Itraconazole

Oral Solution of Itraconazole

Primary outcome measure

Dose limiting toxicities (DLTs) (Phase 1) [ Time Frame: Within the first 21 days of the first neladalkib (NVL-655) dose ]
Recommended Phase 2 Dose (RP2D) (Phase 1) [ Time Frame: Within 21 days of last patient dosed during escalation ]
Objective Response Rate (ORR) (Phase 2) [ Time Frame: 2-3 years after first patient dosed. ]
Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 1) [ Time Frame: Approximately 3 years ]
Area under the curve of repaglinide (Phase 2 DDI sub-study) [ Time Frame: Pre-dose and up to 24 hours post-dose ]
Area under the curve of midazolam (Phase 2 DDI sub-study) [ Time Frame: Pre-dose and up to 24 hours post-dose ]
Area under the curve of neladalkib (NVL-655) (Phase 2 DDI sub-study) [ Time Frame: Pre-dose and up to 24 hours post-dose ]

Central Contacts and Locations

Central contacts

Nuvalent Clinical Trial

857-357-7000 clinicaltrials@nuvalent.com

Locations

University of California Irvine Medical Center

Recruiting

Orange, California, United States, 92868

Principal Investigator:

Misako Nagasaka, MD

University of California, Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

Principal Investigator:

Jonathan Riess, MD

Stanford Cancer Institute

Recruiting

Stanford, California, United States, 94305

Principal Investigator:

Joel Neal, MD, PhD

University of Colorado Cancer Center

Recruiting

Aurora, Colorado, United States, 80045

Principal Investigator:

Ross Camidge, MD, PhD

Georgetown University Medical Center

Recruiting

Washington D.C., District of Columbia, United States, 20007

Principal Investigator:

Joshua Reuss, MD

University of Miami; Sylvester Cancer Center

Recruiting

Miami, Florida, United States, 33136

Principal Investigator:

Gilberto de Lima Lopes, MD

Winship Cancer Institute, Emory University

Recruiting

Atlanta, Georgia, United States, 30322

Principal Investigator:

Ticiana Leal, MD

University of Chicago Medical Center

Recruiting

Chicago, Illinois, United States, 60637

Principal Investigator:

Marina Garassino, MD

John Hopkins University

Recruiting

Baltimore, Maryland, United States, 21224

Principal Investigator:

Vincent Lam, MD

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Principal Investigator:

Jessica Lin, MD

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Principal Investigator:

Alice Shaw, MD

Henry Ford Cancer Institute

Recruiting

Detroit, Michigan, United States, 48202

Principal Investigator:

Bindu Potugari, MD

Washington University School of Medicine Siteman Cancer Center

Recruiting

St Louis, Missouri, United States, 63310

Principal Investigator:

Saiama Waqar, MD

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

Recruiting

New York, New York, United States, 10016

Principal Investigator:

Elaine Shum, MD

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Principal Investigator:

Alexander Drilon, MD

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27705

Principal Investigator:

Thomas Stinchcombe, MD

OSU Brain & Spine Hospital

Recruiting

Columbus, Ohio, United States, 43210

Principal Investigator:

Logan Roof, MD, MSCR

University of Pennsylvania, Abramson Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Principal Investigator:

Charu Aggarwal, MD

Sarah Cannon

Recruiting

Nashville, Tennessee, United States, 37203

Principal Investigator:

Melissa Johnson, MD

Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109

Principal Investigator:

Christina Baik, MD, MPH

Cross Cancer Institute

Recruiting

Edmonton, Alberta, Canada, T6G 1Z2

Principal Investigator:

Quincy Siu Chung Chu, MD

BC Cancer Center

Recruiting

Vancouver, British Columbia, Canada, VZ 4E6

Principal Investigator:

Barbara Melosky, MD

The Ottawa Hospital Cancer Center

Recruiting

Ottawa, Ontario, Canada, K1H 8L6

Principal Investigator:

Garth Nicholas, MD

Princess Margaret Cancer Centre

Recruiting

Toronto, Ontario, Canada, M5G 0A3

Principal Investigator:

Geoffrey Liu, M.D.

More Information

Sponsor

Nuvalent Inc.

Last update posted

May 27, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-16. This information was provided to ClinicalTrials.gov by Nuvalent Inc. on 2026-05-27. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.