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Trial record 1 of 1 for:    NVL-655-01
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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)

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ClinicalTrials.gov Identifier: NCT05384626
Recruitment Status : Recruiting
First Posted : May 20, 2022
Last Update Posted : April 15, 2024
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 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.


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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 470 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
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.
Drug: NVL-655
Oral Tablet of NVL-655

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.
Drug: NVL-655
Oral Tablet of NVL-655

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.
Drug: NVL-655
Oral Tablet of NVL-655

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.
Drug: NVL-655
Oral Tablet of NVL-655

Experimental: Cohort 2e
Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts.
Drug: NVL-655
Oral Tablet of NVL-655

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.
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) (Phase 1) [ 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

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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

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

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

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

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

  15. Progression-free survival (PFS) [ Time Frame: 2-3 years after first patient dosed ]
    Determine PFS of NVL-655 until radiographic disease progression or death

  16. Overall survival (OS) (Phase 2) [ Time Frame: Approximately 3 years ]
    Determine OS

  17. Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 2) [ Time Frame: Approximately 3 years ]
    Incidence and severity of treatment-emergent adverse events (TEAEs)

  18. Quality of life assessment [ Time Frame: 2-3 years after first patient dosed ]
    Measure the quality of life in patients with cancer and/or lung cancer.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 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.

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 clinicaltrials@nuvalent.com

Locations
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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: April 15, 2024
Last Verified: May 2023

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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