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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05384626
Recruitment Status : Recruiting
First Posted : May 20, 2022
Last Update Posted : June 27, 2022
Sponsor:
Information provided by (Responsible Party):
Nuvalent Inc.

Brief Summary:

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 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.


Condition or disease Intervention/treatment Phase
Locally Advanced Solid Tumor Metastatic Solid Tumor Drug: NVL-655 Phase 1 Phase 2

Detailed Description:

In Phase 2, study patients will be enrolled into 4 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, brigatinib)
  • Cohort 2b: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received 2-3 prior 1st or 2nd-generation ALK TKIs (crizotinib, ceritinib, alectinib, brigatinib)
  • Cohort 2c: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received 2-3 prior ALK TKIs, with lorlatinib in the 2nd or 3rd line
  • Cohort 2d: Patients with other solid tumors harboring an ALK rearrangement or activating ALK mutation, including patients with NSCLC not eligible for cohorts 2a-c, who have received ≥1 prior systemic anticancer therapy, or for whom no satisfactory standard therapy exists

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 214 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of the Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor NVL-655 in Patients With Advanced NSCLC and Other Solid Tumors (ALKOVE-1)
Actual Study Start Date : June 9, 2022
Estimated Primary Completion Date : February 2026
Estimated Study Completion Date : March 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1 dose escalation
NVL-655 oral daily dosing
Drug: NVL-655
Oral Tablet of NVL-655

Experimental: Cohort 2a
ALK+ NSCLC treated with 1 prior 2nd-generation ALK TKI therapy
Drug: NVL-655
Oral Tablet of NVL-655

Experimental: Cohort 2b
ALK+ NSCLC treated with 2-3 prior 1st or 2nd-generation ALK TKIs
Drug: NVL-655
Oral Tablet of NVL-655

Experimental: Cohort 2c
ALK+ NSCLC treated with 2-3 prior ALK TKIs, with lorlatinib in the 2nd or 3rd line
Drug: NVL-655
Oral Tablet of NVL-655

Experimental: Cohort 2d
ALK+ solid tumors including patients with NSCLC not eligible for cohorts 2a-c, treated with ≥1 prior systemic anticancer therapy, or for whom no satisfactory standard therapy exists
Drug: NVL-655
Oral Tablet of NVL-655




Primary Outcome Measures :
  1. Dose limiting toxicities (DLTs) (Phase 1) [ Time Frame: Within the first 21 days of the first NVL-655 dose ]
    Define the dose limiting toxicities (DLTs)

  2. Recommended Phase 2 Dose (RP2D) [ Time Frame: Within 21 days of last patient dosed during escalation ]
    To determine the RP2D

  3. Objective Response Rate (ORR) (Phase 2) [ Time Frame: 2-3 years after first patient dosed. ]
    To determine ORR as assessed by BICR


Secondary Outcome Measures :
  1. Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 [ Time Frame: Approximately 3 years ]
    Incidence and severity of treatment-emergent adverse events (TEAEs)

  2. Maximum plasma concentration, (Cmax) of NVL-655 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
    To determine the maximum plasma concentration (Cmax) of NVL

  3. Plasma concentration at the end of the dosing interval (Ctau) of NVL-655 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
    To determine the plasma concentration at the end of the dosing interval (Ctau) of NVL-655

  4. Average plasma concentration (Cavg) of NVL-655 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
    To determine the average plasma concentration (Cavg) of NVL-655

  5. Time of maximum concentration (Tmax) of NVL-655 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
    To determine the time of maximum concentration (Tmax) of NVL-655

  6. Area under the curve at the end of the dosing interval (AUCtau) of NVL-655 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
    To determine the area under the curve at the end of the dosing interval (AUCtau) of NVL-655

  7. Area under the curve from time 0 to 24 (AUC0-24) of NVL-655 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
    To determine the area under the curve from time 0 to 24 (AUC0-24) of NVL-655

  8. Area under the curve from time 0 to infinity (AUCinf) of NVL-655 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
    To determine the area under the curve from time 0 to infinity (AUCinf) of NVL-655

  9. Oral clearance (CL/F) of NVL-655 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
    To determine the oral clearance (CL/F) of NVL-655

  10. Volume of distribution (Vz/F) of NVL-655 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
    To determine the volume of distribution (Vz/F) of NVL-655

  11. Half-life (t1/2) of NVL-655 [ Time Frame: Pre-dose and up to 24 hours post-dose ]
    To determine the half-life (t1/2) of NVL-655

  12. Objective response rate (ORR) (Phase 1) [ Time Frame: 2-3 years after first patient dosed ]
    Determine ORR as assessed by BICR

  13. Duration of response (DOR) [ Time Frame: 2-3 years after first patient dosed ]
    Determine DOR of NVL-655 until radiographic disease progression or death

  14. Clinical benefit rate (CBR) [ Time Frame: 2-3 years after first patient dosed ]
    Determine CBR of NVL-655

  15. Time to response [ Time Frame: Approximately 3 years ]
    Determine time to response of NVL-655

  16. Progression-free survival (PFS) [ Time Frame: 2-3 years after first patient dosed ]
    Determine PFS of NVL-520 until radiographic disease progression or death

  17. Overall survival (OS) [ Time Frame: Approximately 3 years ]
    Determine OS



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥18 years Phase 2 Cohort 2d 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. Cohorts 2a, 2b, and 2c: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with a documented ALK rearrangement
    2. Cohort 2d: histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05384626


Contacts
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Contact: Tina Kehrig 857-357-7000 medical@nuvalent.com

Locations
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United States, California
University of California Irvine Medical Center Not yet recruiting
Orange, California, United States, 92868
United States, Colorado
University of Colorado Cancer Center Not yet recruiting
Denver, Colorado, United States, 80045
United States, Massachusetts
Mass General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
United States, Michigan
Henry Ford Cancer Institute Not yet recruiting
Detroit, Michigan, United States, 48202
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
United States, Tennessee
Sarah Cannon Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Nuvalent Inc.
Investigators
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Study Director: Viola Zhu, MD, PHD Nuvalent Inc.
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Responsible Party: Nuvalent Inc.
ClinicalTrials.gov Identifier: NCT05384626    
Other Study ID Numbers: NVL-655-01
First Posted: May 20, 2022    Key Record Dates
Last Update Posted: June 27, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms