Clinical trial NCT05384626: A Study of NVL-655 in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Locally Advanced Solid Tumor
Metastatic Solid Tumor
Lead sponsor: Nuvalent Inc.
Sponsor class: INDUSTRY
First posted: 2022-05-20
Enrollment: 470
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Dose limiting toxicities (DLTs) (Phase 1)
timeFrame: Within the first 21 days of the first NVL-655 dose
measure: Recommended Phase 2 Dose (RP2D) (Phase 1)
timeFrame: Within 21 days of last patient dosed during escalation
measure: Objective Response Rate (ORR) (Phase 2)
timeFrame: 2-3 years after first patient dosed.
measure: Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 1)
timeFrame: Approximately 3 years
Secondary outcomes:
measure: Maximum plasma concentration, (Cmax) of NVL-655
timeFrame: Pre-dose and up to 24 hours post-dose
measure: Plasma concentration at the end of the dosing interval (Ctau) of NVL-655
timeFrame: Pre-dose and up to 24 hours post-dose
measure: Average plasma concentration (Cavg) of NVL-655
timeFrame: Pre-dose and up to 24 hours post-dose
measure: Time of maximum concentration (Tmax) of NVL-655
timeFrame: Pre-dose and up to 24 hours post-dose
measure: Area under the curve at the end of the dosing interval (AUCtau) of NVL-655
timeFrame: Pre-dose and up to 24 hours post-dose
measure: Area under the curve from time 0 to 24 (AUC0-24) of NVL-655
timeFrame: Pre-dose and up to 24 hours post-dose
measure: Area under the curve from time 0 to infinity (AUCinf) of NVL-655
timeFrame: Pre-dose and up to 24 hours post-dose
measure: Oral clearance (CL/F) of NVL-655
timeFrame: Pre-dose and up to 24 hours post-dose
measure: Volume of distribution (Vz/F) of NVL-655
timeFrame: Pre-dose and up to 24 hours post-dose
measure: Half-life (t1/2) of NVL-655
timeFrame: Pre-dose and up to 24 hours post-dose
measure: Objective response rate (ORR) (Phase 1)
timeFrame: 2-3 years after first patient dosed
measure: Duration of response (DOR)
timeFrame: 2-3 years after first patient dosed
measure: Clinical benefit rate (CBR)
timeFrame: 2-3 years after first patient dosed
measure: Time to response
timeFrame: Approximately 3 years
measure: Progression-free survival (PFS)
timeFrame: 2-3 years after first patient dosed
measure: Overall survival (OS) (Phase 2)
timeFrame: Approximately 3 years
measure: Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 2)
timeFrame: Approximately 3 years
measure: Quality of life assessment
timeFrame: 2-3 years after first patient dosed
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Sacramento
country: United States
facility: University of California, Davis Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute
state: California
city: Denver
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Miami
country: United States
facility: University of Miami; Sylvester Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Boston
country: United States
facility: Mass General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine Siteman Cancer Center
state: Missouri
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: OSU Brain & Spine Hospital
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania, Abramson Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven Campus Gastthuisberg
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Center
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Vancouver
country: Canada
facility: BC Cancer
city: Lyon
country: France
facility: Centre Leon Berard
city: Saint-Herblain
country: France
facility: Chu De Nantes
city: Toulouse Cedex
country: France
facility: Institut Claudius Regaud
city: Villejuif
country: France
facility: Institute Gustave Roussy
city: Cologne
country: Germany
facility: Universitatsklinikum Koln - University Hospital Cologne
city: Grosshansdorf
country: Germany
facility: LungenClinic Grosshansdorf GmbH
city: Heidelberg
country: Germany
facility: Universkitatsklinikum Heidelberg - University Hospital Heidelberg
city: Ancona
country: Italy
facility: Azienda Ospedaliera Universitaria Ospedali Riuniti Umberto
city: Bari
country: Italy
facility: IRCCS Istituto Tumori "G. Paolo II"
city: Milano
country: Italy
facility: Instituto Europeo di Oncologia
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Rome
country: Italy
facility: Regina Elena Institute for Cancer Research
city: Veneto
country: Italy
facility: Instituto Oncologico Veneto
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: Center Institute Hospital of JFCR
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Capital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Capital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute
city: Groningen
country: Netherlands
facility: University Medical Center Groningen (UMCG)
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario de A Coruna
city: Barcelona
country: Spain
facility: UOMI Cancer Center
city: Barcelona
country: Spain
facility: Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico Svizzera Italiana
city: Spitalstrasse
country: Switzerland
facility: Luzerner Kantonsspital
city: Taichung City
country: Taiwan
facility: Chung-Shan Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: Surrey
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre
city: London
country: United Kingdom
facility: The Royal Marsden - Chelsea
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: Nuvalent Inc.
name: Viola Zhu, MD, PHD
role: STUDY_DIRECTOR
References: