Trial record 1 of 1 for:
NVL-655-01
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 |
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Recruitment Status :
Recruiting
First Posted : May 20, 2022
Last Update Posted : September 28, 2023
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Sponsor:
Nuvalent Inc.
Information provided by (Responsible Party):
Nuvalent Inc.
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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 |
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
| 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 |
|---|---|
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Experimental: Phase 1 dose escalation
NVL-655 oral daily dosing
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Drug: NVL-655
Oral Tablet of NVL-655 |
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Experimental: Cohort 2a
ALK+ NSCLC treated with 1 prior 2nd-generation ALK TKI therapy
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Drug: NVL-655
Oral Tablet of NVL-655 |
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Experimental: Cohort 2b
ALK+ NSCLC treated with 2-3 prior 1st or 2nd-generation ALK TKIs
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Drug: NVL-655
Oral Tablet of NVL-655 |
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Experimental: Cohort 2c
ALK+ NSCLC treated with 2-3 prior ALK TKIs, with lorlatinib in the 2nd or 3rd line
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Drug: NVL-655
Oral Tablet of NVL-655 |
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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
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Drug: NVL-655
Oral Tablet of NVL-655 |
Primary Outcome Measures :
- 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)
- Recommended Phase 2 Dose (RP2D) [ Time Frame: Within 21 days of last patient dosed during escalation ]To determine the RP2D
- 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 :
- 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)
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Objective response rate (ORR) (Phase 1) [ Time Frame: 2-3 years after first patient dosed ]Determine ORR as assessed by BICR
- Duration of response (DOR) [ Time Frame: 2-3 years after first patient dosed ]Determine DOR of NVL-655 until radiographic disease progression or death
- Clinical benefit rate (CBR) [ Time Frame: 2-3 years after first patient dosed ]Determine CBR of NVL-655
- Time to response [ Time Frame: Approximately 3 years ]Determine time to response of NVL-655
- Progression-free survival (PFS) [ Time Frame: 2-3 years after first patient dosed ]Determine PFS of NVL-520 until radiographic disease progression or death
- 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:
- Age ≥18 years Phase 2 Cohort 2d only: Age ≥12 years and weighing >40 kg.
- Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation.
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Phase 2
- Cohorts 2a, 2b, and 2c: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with a documented ALK rearrangement
- Cohort 2d: histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation
- 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
- Adequate organ function and bone marrow reserve
Exclusion criteria:
- Patient's cancer has a known oncogenic driver alteration other than ALK.
- Known allergy/hypersensitivity to excipients of NVL-655.
- Major surgery within 4 weeks of the study entry
- Ongoing or anticancer therapy
- 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
| Contact: Tina Kehrig | 857-357-7000 | clinicaltrials@nuvalent.com |
Locations
Show 25 study locations
Sponsors and Collaborators
Nuvalent Inc.
Investigators
| Study Director: | Viola Zhu, MD, PHD | Nuvalent Inc. |
| 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: | September 28, 2023 |
| Last Verified: | May 2023 |
| 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 |