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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05384626




Registration number
NCT05384626
Ethics application status
Date submitted
17/05/2022
Date registered
20/05/2022
Date last updated
10/06/2024

Titles & IDs
Public title
A Study of NVL-655 in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Scientific 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)
Secondary ID [1] 0 0
NVL-655-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced Solid Tumor 0 0
Metastatic Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NVL-655

Experimental: Phase 1 dose escalation - NVL-655 oral daily dosing

Experimental: 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.

Experimental: 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.

Experimental: 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.

Experimental: 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.

Experimental: Cohort 2e - Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts.

Experimental: 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.


Treatment: Drugs: NVL-655
Oral Tablet of NVL-655
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose limiting toxicities (DLTs) (Phase 1)
Timepoint [1] 0 0
Within the first 21 days of the first NVL-655 dose
Primary outcome [2] 0 0
Recommended Phase 2 Dose (RP2D) (Phase 1)
Timepoint [2] 0 0
Within 21 days of last patient dosed during escalation
Primary outcome [3] 0 0
Objective Response Rate (ORR) (Phase 2)
Timepoint [3] 0 0
2-3 years after first patient dosed.
Primary outcome [4] 0 0
Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 1)
Timepoint [4] 0 0
Approximately 3 years
Secondary outcome [1] 0 0
Maximum plasma concentration, (Cmax) of NVL-655
Timepoint [1] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [2] 0 0
Plasma concentration at the end of the dosing interval (Ctau) of NVL-655
Timepoint [2] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [3] 0 0
Average plasma concentration (Cavg) of NVL-655
Timepoint [3] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [4] 0 0
Time of maximum concentration (Tmax) of NVL-655
Timepoint [4] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [5] 0 0
Area under the curve at the end of the dosing interval (AUCtau) of NVL-655
Timepoint [5] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [6] 0 0
Area under the curve from time 0 to 24 (AUC0-24) of NVL-655
Timepoint [6] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [7] 0 0
Area under the curve from time 0 to infinity (AUCinf) of NVL-655
Timepoint [7] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [8] 0 0
Oral clearance (CL/F) of NVL-655
Timepoint [8] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [9] 0 0
Volume of distribution (Vz/F) of NVL-655
Timepoint [9] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [10] 0 0
Half-life (t1/2) of NVL-655
Timepoint [10] 0 0
Pre-dose and up to 24 hours post-dose
Secondary outcome [11] 0 0
Objective response rate (ORR) (Phase 1)
Timepoint [11] 0 0
2-3 years after first patient dosed
Secondary outcome [12] 0 0
Duration of response (DOR)
Timepoint [12] 0 0
2-3 years after first patient dosed
Secondary outcome [13] 0 0
Clinical benefit rate (CBR)
Timepoint [13] 0 0
2-3 years after first patient dosed
Secondary outcome [14] 0 0
Time to response
Timepoint [14] 0 0
Approximately 3 years
Secondary outcome [15] 0 0
Progression-free survival (PFS)
Timepoint [15] 0 0
2-3 years after first patient dosed
Secondary outcome [16] 0 0
Overall survival (OS) (Phase 2)
Timepoint [16] 0 0
Approximately 3 years
Secondary outcome [17] 0 0
Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 2)
Timepoint [17] 0 0
Approximately 3 years
Secondary outcome [18] 0 0
Quality of life assessment
Timepoint [18] 0 0
2-3 years after first patient dosed

Eligibility
Key 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
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/06/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2026
Actual
Sample size
Target
470
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
France
State/province [18] 0 0
Lyon
Country [19] 0 0
France
State/province [19] 0 0
Saint-Herblain
Country [20] 0 0
France
State/province [20] 0 0
Toulouse Cedex
Country [21] 0 0
France
State/province [21] 0 0
Villejuif
Country [22] 0 0
Italy
State/province [22] 0 0
Bari
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Gyeonggi-do
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Seoul Capital
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Seoul
Country [26] 0 0
Netherlands
State/province [26] 0 0
Groningen
Country [27] 0 0
Singapore
State/province [27] 0 0
Singapore
Country [28] 0 0
Spain
State/province [28] 0 0
A Coruña
Country [29] 0 0
Spain
State/province [29] 0 0
Barcelona
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
Taiwan
State/province [31] 0 0
Tainan
Country [32] 0 0
Taiwan
State/province [32] 0 0
Taipei
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Surrey
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Edinburgh
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Nuvalent Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05384626
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Viola Zhu, MD, PHD
Address 0 0
Nuvalent Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Tina Kehrig
Address 0 0
Country 0 0
Phone 0 0
857-357-7000
Fax 0 0
Email 0 0
clinicaltrials@nuvalent.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05384626