A Study in TKI-naive Patients With Advanced ALK-Positive NSCLC ( ALKAZAR )

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Nuvalent Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Nov 2025 → ongoing

Decision date (initial)

2025-06-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Nuvalent, Inc

External identifiers

EU CT number

2024-517553-26-00

ClinicalTrials.gov

NCT06765109

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others

To evaluate the efficacy of NVL-655 compared to alectinib in patients with treatment-naïve ALK-positive advanced NSCLC

Secondary objectives 3

1. To assess additional measures of efficacy of NVL-655 compared to alectinib in patients with treatment-naïve ALK-positive advanced NSCLC
2. To evaluate the safety and tolerability of NVL-655 compared to alectinib
3. To evaluate and compare patient-reported measures of health-related quality of life (QoL), lung cancer symptoms, patient functioning, and side effects of treatment

Conditions and MedDRA coding

Advanced ALK-positive non-small cell lung cancer (NSCLC)

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

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 1

1. Patients must meet all of the following criteria to be eligible to enroll in the study: 1. Histologically or cytologically confirmed locally advanced (not amenable for multimodality treatment) or metastatic Non-small Cell Lung Cancer (NSCLC) 2. Documented Anaplastic Lymphoma Kinase (ALK) rearrangement via testing of tissue or blood 3. No prior systemic anticancer treatment for NSCLC (adjuvant/neoadjuvant chemotherapy allowed if 12 months prior to randomization; prior ALK tyrosine kinase inhibitor [TKI] such as alectinib is not allowed in any setting) 4. Measurable disease (1 or more target lesions per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) 5. Pretreatment tumor tissue (archived or a fresh biopsy)

Exclusion criteria 1

1. 1. Patient’s cancer has a known oncogenic driver alteration other than ALK. 2. Known allergy/hypersensitivity to excipients of NVL-655 or alectinib. 3. Major surgery within 4 weeks prior to randomization 4. Ongoing or recent radiotherapy as per protocol-specified timeframes prior to randomization 5. Uncontrolled clinically relevant infection requiring systemic therapy 6. Known active tuberculosis, known active Hepatitis B or C 7. QT corrected for heart rate by Fridericia’s formula (QTcF) > 470 msec on repeated assessments 8. Clinically significant cardiovascular disease 9. Brain metastases associated with progressive neurological symptoms or requiring increasing doses of corticosteroids to control CNS disease 10. Active malignancy requiring therapy within 2 years prior to randomization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS)

Secondary endpoints 3

1. 1) - Overall survival (OS) - Progression-free survival (PFS) per investigator assessment - Time to intracranial progression per blinded independent central review (BICR) - Intracranial objective response rate (IC-ORR) - Intracranial duration of response (IC-DOR) - Objective response rate (ORR) - Duration of response (DOR) - Time to intracranial progression, IC-ORR, IC-DOR, ORR, and DOR
2. 2) Incidence and severity of treatment-emergent adverse events (TEAEs) and changes in clinically relevant laboratory parameters
3. 3) Changes in patient-reported outcomes (PROs)

Investigational products

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

Test 2

Comparator 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 13

Locations

13 EU/EEA countries · 71 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 167 files

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

Application history

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