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

Part of paid clinical trials in Orange, California.

Sponsor
Nuvalent Inc.
Study ID
NCT05384626
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Locally Advanced Solid Tumor
  • Metastatic Solid Tumor

Eligibility Criteria

Sex
ALL
Age
12 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Neladalkib (NVL-655) — DRUG
    Oral Tablet of Neladalkib (NVL-655)
  • Midazolam — DRUG
    Oral Solution of Midazolam
  • Repaglinide — DRUG
    Oral Tablet of Repaglinide
  • Itraconazole — DRUG
    Oral Solution of Itraconazole

Study Details

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

Key Dates

Start date
Jun 9, 2022
Status verified
May 2026
Primary completion
Dec 31, 2027
Completion
Jan 31, 2028

Study Design

Enrollment
840 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

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

Primary Outcome Measure

Dose limiting toxicities (DLTs) (Phase 1) [ Time Frame: Within the first 21 days of the first neladalkib (NVL-655) dose ]

Central Contacts

Locations (21)

FacilityCityStateZIPSite coordinators
University of California Irvine Medical CenterOrangeCalifornia92868
Misako Nagasaka, MD (PRINCIPAL_INVESTIGATOR)
University of California, Davis Comprehensive Cancer CenterSacramentoCalifornia95817
Jonathan Riess, MD (PRINCIPAL_INVESTIGATOR)
Stanford Cancer InstituteStanfordCalifornia94305
Joel Neal, MD, PhD (PRINCIPAL_INVESTIGATOR)
University of Colorado Cancer CenterAuroraColorado80045
Ross Camidge, MD, PhD (PRINCIPAL_INVESTIGATOR)
Georgetown University Medical CenterWashington D.C.District of Columbia20007
Joshua Reuss, MD (PRINCIPAL_INVESTIGATOR)
University of Miami; Sylvester Cancer CenterMiamiFlorida33136
Gilberto de Lima Lopes, MD (PRINCIPAL_INVESTIGATOR)
Winship Cancer Institute, Emory UniversityAtlantaGeorgia30322
Ticiana Leal, MD (PRINCIPAL_INVESTIGATOR)
University of Chicago Medical CenterChicagoIllinois60637
Marina Garassino, MD (PRINCIPAL_INVESTIGATOR)
John Hopkins UniversityBaltimoreMaryland21224
Vincent Lam, MD (PRINCIPAL_INVESTIGATOR)
Dana Farber Cancer InstituteBostonMassachusetts02215
Alice Shaw, MD (PRINCIPAL_INVESTIGATOR)
Massachusetts General HospitalBostonMassachusetts02114
Jessica Lin, MD (PRINCIPAL_INVESTIGATOR)
Henry Ford Cancer InstituteDetroitMichigan48202
Bindu Potugari, MD (PRINCIPAL_INVESTIGATOR)
Washington University School of Medicine Siteman Cancer CenterSt LouisMissouri63310
Saiama Waqar, MD (PRINCIPAL_INVESTIGATOR)
Laura & Isaac Perlmutter Cancer Center at NYU Langone HealthNew YorkNew York10016
Elaine Shum, MD (PRINCIPAL_INVESTIGATOR)
Memorial Sloan Kettering Cancer CenterNew YorkNew York10065
Alexander Drilon, MD (PRINCIPAL_INVESTIGATOR)
Duke University Medical CenterDurhamNorth Carolina27705
Thomas Stinchcombe, MD (PRINCIPAL_INVESTIGATOR)
OSU Brain & Spine HospitalColumbusOhio43210
Logan Roof, MD, MSCR (PRINCIPAL_INVESTIGATOR)
University of Pennsylvania, Abramson Cancer CenterPhiladelphiaPennsylvania19104
Charu Aggarwal, MD (PRINCIPAL_INVESTIGATOR)
Sarah CannonNashvilleTennessee37203
Melissa Johnson, MD (PRINCIPAL_INVESTIGATOR)
MD Anderson Cancer CenterHoustonTexas77030-
Fred Hutchinson Cancer CenterSeattleWashington98109
Christina Baik, MD, MPH (PRINCIPAL_INVESTIGATOR)

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By research site
University of California Irvine Medical Center· Orange, CAUniversity of California, Davis Comprehensive Cancer Center· Sacramento, CAStanford Cancer Institute· Stanford, CAUniversity of Colorado Cancer Center· Aurora, COGeorgetown University Medical Center· Washington D.C., DCUniversity of Miami; Sylvester Cancer Center· Miami, FL

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