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

Metastatic Solid Tumor Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05384626
• Other study ID #: NVL-655-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 9, 2022
• Est. completion date: March 2026

Study information

• Verified date: May 2023
• Source: Nuvalent Inc.
• Contact: Tina Kehrig
• Phone: 857-357-7000
• Email: clinicaltrials[@]nuvalent.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 470
• Est. completion date: March 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Locally Advanced Solid Tumor
• Metastatic Solid Tumor
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Royal North Shore Hospital	Saint Leonards	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
France	Centre Leon Berard	Lyon
France	Chu De Nantes	Saint-Herblain
France	Institut Claudius Regaud	Toulouse Cedex
France	Institute Gustave Roussy	Villejuif
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul Capital
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul	Seoul Capital
Singapore	National Cancer Centre Singapore	Singapore
Spain	Complejo Hospitalario Universitario de A Coruna	A Coruña
Spain	UOMI Cancer Center	Barcelona
Spain	Vall d'Hebron	Barcelona
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Royal Marsden Hospital	Sutton	Surrey
United States	John Hopkins University	Baltimore	Maryland
United States	Mass General Hospital	Boston	Massachusetts
United States	OSU Brain & Spine Hospital	Columbus	Ohio
United States	University of Colorado Cancer Center	Denver	Colorado
United States	Henry Ford Cancer Institute	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Miami; Sylvester Cancer Center	Miami	Florida
United States	Sarah Cannon	Nashville	Tennessee
United States	Laura & Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of California Irvine Medical Center	Orange	California
United States	University of California, Davis Comprehensive Cancer Center	Sacramento	California
United States	Washington University School of Medicine Siteman Cancer Center	Saint Louis	Missouri
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Stanford Cancer Institute	Stanford	California
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Nuvalent Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Korea, Republic of,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicities (DLTs) (Phase 1)	Define the dose limiting toxicities (DLTs)	Within the first 21 days of the first NVL-655 dose
Primary	Recommended Phase 2 Dose (RP2D) (Phase 1)	To determine the RP2D	Within 21 days of last patient dosed during escalation
Primary	Objective Response Rate (ORR) (Phase 2)	To determine ORR as assessed by BICR	2-3 years after first patient dosed.
Primary	Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 1)	Incidence and severity of treatment-emergent adverse events (TEAEs)	Approximately 3 years
Secondary	Maximum plasma concentration, (Cmax) of NVL-655	To determine the maximum plasma concentration (Cmax) of NVL	Pre-dose and up to 24 hours post-dose
Secondary	Plasma concentration at the end of the dosing interval (Ctau) of NVL-655	To determine the plasma concentration at the end of the dosing interval (Ctau) of NVL-655	Pre-dose and up to 24 hours post-dose
Secondary	Average plasma concentration (Cavg) of NVL-655	To determine the average plasma concentration (Cavg) of NVL-655	Pre-dose and up to 24 hours post-dose
Secondary	Time of maximum concentration (Tmax) of NVL-655	To determine the time of maximum concentration (Tmax) of NVL-655	Pre-dose and up to 24 hours post-dose
Secondary	Area under the curve at the end of the dosing interval (AUCtau) of NVL-655	To determine the area under the curve at the end of the dosing interval (AUCtau) of NVL-655	Pre-dose and up to 24 hours post-dose
Secondary	Area under the curve from time 0 to 24 (AUC0-24) of NVL-655	To determine the area under the curve from time 0 to 24 (AUC0-24) of NVL-655	Pre-dose and up to 24 hours post-dose
Secondary	Area under the curve from time 0 to infinity (AUCinf) of NVL-655	To determine the area under the curve from time 0 to infinity (AUCinf) of NVL-655	Pre-dose and up to 24 hours post-dose
Secondary	Oral clearance (CL/F) of NVL-655	To determine the oral clearance (CL/F) of NVL-655	Pre-dose and up to 24 hours post-dose
Secondary	Volume of distribution (Vz/F) of NVL-655	To determine the volume of distribution (Vz/F) of NVL-655	Pre-dose and up to 24 hours post-dose
Secondary	Half-life (t1/2) of NVL-655	To determine the half-life (t1/2) of NVL-655	Pre-dose and up to 24 hours post-dose
Secondary	Objective response rate (ORR) (Phase 1)	Determine ORR as assessed by BICR	2-3 years after first patient dosed
Secondary	Duration of response (DOR)	Determine DOR of NVL-655 until radiographic disease progression or death	2-3 years after first patient dosed
Secondary	Clinical benefit rate (CBR)	Determine CBR of NVL-655	2-3 years after first patient dosed
Secondary	Time to response	Determine time to response of NVL-655	Approximately 3 years
Secondary	Progression-free survival (PFS)	Determine PFS of NVL-655 until radiographic disease progression or death	2-3 years after first patient dosed
Secondary	Overall survival (OS) (Phase 2)	Determine OS	Approximately 3 years
Secondary	Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 2)	Incidence and severity of treatment-emergent adverse events (TEAEs)	Approximately 3 years
Secondary	Quality of life assessment	Measure the quality of life in patients with cancer and/or lung cancer.	2-3 years after first patient dosed