A Study of NVL-655 in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Study Details
Study Description
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 |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
In Phase 2, study patients will be enrolled into 4 distinct cohorts:
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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)
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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)
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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
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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 Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Dose limiting toxicities (DLTs) (Phase 1) [Within the first 21 days of the first NVL-655 dose]
Define the dose limiting toxicities (DLTs)
- Recommended Phase 2 Dose (RP2D) [Within 21 days of last patient dosed during escalation]
To determine the RP2D
- Objective Response Rate (ORR) (Phase 2) [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 [Approximately 3 years]
Incidence and severity of treatment-emergent adverse events (TEAEs)
- Maximum plasma concentration, (Cmax) of NVL-655 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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) [2-3 years after first patient dosed]
Determine ORR as assessed by BICR
- Duration of response (DOR) [2-3 years after first patient dosed]
Determine DOR of NVL-655 until radiographic disease progression or death
- Clinical benefit rate (CBR) [2-3 years after first patient dosed]
Determine CBR of NVL-655
- Time to response [Approximately 3 years]
Determine time to response of NVL-655
- Progression-free survival (PFS) [2-3 years after first patient dosed]
Determine PFS of NVL-520 until radiographic disease progression or death
- Overall survival (OS) [Approximately 3 years]
Determine OS
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥18 years Phase 2 Cohort 2d only: Age ≥12 years and weighing >40 kg.
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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
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Cohorts 2a, 2b, and 2c: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with a documented ALK rearrangement
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Cohort 2d: histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation
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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
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Adequate organ function and bone marrow reserve
Exclusion criteria:
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Patient's cancer has a known oncogenic driver alteration other than ALK.
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Known allergy/hypersensitivity to excipients of NVL-655.
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Major surgery within 4 weeks of the study entry
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Ongoing or anticancer therapy
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Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California Irvine Medical Center | Orange | California | United States | 92868 |
| 2 | University of Colorado Cancer Center | Denver | Colorado | United States | 80045 |
| 3 | Mass General Hospital | Boston | Massachusetts | United States | 02114 |
| 4 | Henry Ford Cancer Institute | Detroit | Michigan | United States | 48202 |
| 5 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 6 | Sarah Cannon | Nashville | Tennessee | United States | 37203 |
| 7 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Nuvalent Inc.
Investigators
- Study Director: Viola Zhu, MD, PHD, Nuvalent Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NVL-655-01