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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Nuvalent Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Nov 2022 → ongoing

Decision date (initial)

2024-11-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Nuvalent, Inc.

External identifiers

EU CT number

2024-514266-39-00

EudraCT number

2022-000122-21

ClinicalTrials.gov

NCT05384626

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Dose response, Pharmacodynamic, Pharmacokinetic, Therapy

Phase 1 - To evaluate the overall safety and tolerability of NVL-655
Phase 1 - To determine the RP2D and, if applicable, the MTD of NVL-655 in patients with advanced ALK-positive solid tumors
Phase 2 - To evaluate the efficacy of NVL-655 at the RP2D in patients with advanced ALK-positive NSCLC, including those with ALK resistance mutations, and other solid tumors

Secondary objectives 7

1. Phase 1 - To characterize the PK profile of NVL-655
2. Phase 1 - To evaluate preliminary antitumor activity of NVL-655 in patients with advanced ALK-positive solid tumors
3. Phase 2 - To assess additional measures of clinical efficacy in patients with ALK-positive NSCLC, including those with ALK resistance mutations, and other solid tumors
4. Phase 2 - To evaluate the intracranial antitumor activity of NVL-655 at the RP2D in patients with advanced ALK-positive NSCLC and other solid tumors
5. Phase 2 - To characterize the safety and tolerability of NVL-655 at the RP2D
6. Phase 2 - To confirm the PK profile of NVL-655 at the RP2D
7. Phase 2 - To assess treatment-related symptoms and general health status using validated instruments of patient-reported outcomes (PROs) in patients treated with NVL-655

Conditions and MedDRA coding

Advanced Non-Small Cell Lung Cancer (NSCLC) and Other Solid Tumors with ALK rearrangement or activating ALK mutation

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003648-PIP01-24

Plan to share IPD

No

IPD plan description

There is currently no IPD sharing plan in place. If needed the plan will be developed ahead of any manuscript preparation.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Age ≥ 18 years
2. Phase 2 Cohort 2f only: Age ≥ 12 years and weight > 40 kg.
3. Disease criteria: Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation.
4. Disease criteria: Cohorts 2a, 2b, 2c, 2d, and 2e: Histologically or cytologically confirmed locally advanced or metastatic ALK rearrangement or activating ALK mutation
5. Disease criteria: Cohort 2f: Histologically or cytologically confirmed locally advanced or metastatic solid tumor (including NSCLC not eligible for Cohorts 2a-2e) with a documented ALK rearrangement or activating ALK mutation.
6. Prior anticancer treatment: Phase 1: Must have evaluable disease (target or nontarget) according to RECIST 1.1
7. Prior anticancer treatment: Phase 2: Must have measurable disease, defined as ≥1 radiologically measurable target lesion according to RECIST 1.1
8. Pre-treatment tumor tissue
9. Please refer to the protocol for further criteria

Exclusion criteria 6

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 first dose of study drug
4. Ongoing or recent anticancer therapy
5. Ongoing or recent radiation therapy
6. Please refer to the protocol for further criteria

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Phase 1 - Incidence and severity of TEAEs and changes in clinically relevant laboratory parameters
2. Phase 1 - RP2D and, if applicable, the MTD
3. Phase 2 - ORR according to RECIST 1.1

Secondary endpoints 7

1. Phase 1 - PK parameters of NVL-655
2. Phase 1 - ORR according to RECIST 1.1 assessment
3. Phase 2 - DOR
4. Phase 2 - IC-ORR
5. Phase 2 - Incidence and severity of TEAEs and changes in clinically relevant laboratory parameters
6. Phase 2 - PK parameters of NVL-655
7. Phase 2 - Changes in PROs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Nuvalent Inc.

Sponsor organisation

Nuvalent Inc.

Address

1 Broadway Floor 14th

City

Cambridge

Postcode

02142-1187

Country

United States

Scientific contact point

Organisation

Nuvalent Inc.

Contact name

Medical

Public contact point

Organisation

Nuvalent Inc.

Contact name

Medical

Third parties 14

Locations

6 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 116 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications