A Study of NVL-655 in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
- Conditions
- Locally Advanced Solid TumorMetastatic Solid Tumor
- Interventions
- Registration Number
- NCT05384626
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 470
-
Age ≥18 years, Phase 2 Cohort 2f 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.
-
Phase 2
- Phase 2 Cohorts except 2f: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with a documented ALK rearrangement
- 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.
-
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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 2d NVL-655 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. Phase 1 dose escalation NVL-655 NVL-655 oral daily dosing Cohort 2c NVL-655 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 2a NVL-655 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 NVL-655 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 2e NVL-655 Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts. Cohort 2f NVL-655 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.
- Primary Outcome Measures
Name Time Method 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) (Phase 1) 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
Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 1) Approximately 3 years Incidence and severity of treatment-emergent adverse events (TEAEs)
- Secondary Outcome Measures
Name Time Method 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-655 until radiographic disease progression or death
Overall survival (OS) (Phase 2) Approximately 3 years Determine OS
Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 2) Approximately 3 years Incidence and severity of treatment-emergent adverse events (TEAEs)
Quality of life assessment 2-3 years after first patient dosed Measure the quality of life in patients with cancer and/or lung cancer.
Trial Locations
- Locations (70)
Universitatsklinikum Koln - University Hospital Cologne
🇩🇪Cologne, Germany
Universkitatsklinikum Heidelberg - University Hospital Heidelberg
🇩🇪Heidelberg, Germany
Okayama University Hospital
🇯🇵Okayama, Japan
Wakayama Medical University Hospital
🇯🇵Wakayama, Japan
University of California Irvine Medical Center
🇺🇸Orange, California, United States
University of California, Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Henry Ford Cancer Institute
🇺🇸Detroit, Michigan, United States
Stanford Cancer Institute
🇺🇸Stanford, California, United States
University of Colorado Cancer Center
🇺🇸Denver, Colorado, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
University of Miami; Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
John Hopkins University
🇺🇸Baltimore, Maryland, United States
Mass General Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine Siteman Cancer Center
🇺🇸Saint Louis, Missouri, 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
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
OSU Brain & Spine Hospital
🇺🇸Columbus, Ohio, United States
University of Pennsylvania, Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Sarah Cannon
🇺🇸Nashville, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Royal North Shore Hospital
🇦🇺Saint Leonards, New South Wales, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Universitaire Ziekenhuizen Leuven Campus Gastthuisberg
🇧🇪Leuven, Belgium
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
The Ottawa Hospital Cancer Center
🇨🇦Ottawa, Ontario, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
BC Cancer
🇨🇦Vancouver, Canada
Centre Leon Berard
🇫🇷Lyon, France
Chu De Nantes
🇫🇷Saint-Herblain, France
Institut Claudius Regaud
🇫🇷Toulouse Cedex, France
Institute Gustave Roussy
🇫🇷Villejuif, France
LungenClinic Grosshansdorf GmbH
🇩🇪Grosshansdorf, Germany
Azienda Ospedaliera Universitaria Ospedali Riuniti Umberto
🇮🇹Ancona, Italy
IRCCS Istituto Tumori "G. Paolo II"
🇮🇹Bari, Italy
Instituto Europeo di Oncologia
🇮🇹Milano, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milan, Italy
Ospedale Santa Maria delle Croci
🇮🇹Ravenna, Italy
Regina Elena Institute for Cancer Research
🇮🇹Rome, Italy
Instituto Oncologico Veneto
🇮🇹Veneto, Italy
Kindai University Hospital
🇯🇵Osaka, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
Center Institute Hospital of JFCR
🇯🇵Tokyo, Japan
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, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
The Netherlands Cancer Institute
🇳🇱Amsterdam, Netherlands
University Medical Center Groningen (UMCG)
🇳🇱Groningen, Netherlands
National University Hospital
🇸🇬Singapore, Singapore
National Cancer Centre Singapore
🇸🇬Singapore, Singapore
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, Spain
Istituto Oncologico Svizzera Italiana
🇨🇭Bellinzona, Switzerland
Luzerner Kantonsspital
🇨🇭Spitalstrasse, Switzerland
Chung-Shan Medical University Hospital
🇨🇳Taichung City, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Royal Marsden Hospital
🇬🇧Sutton, Surrey, United Kingdom
Edinburgh Cancer Centre
🇬🇧Edinburgh, United Kingdom
The Royal Marsden - Chelsea
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom