Detail Article

Informations générales (source: ClinicalTrials.gov)

Numéro NCT

NCT05384626 En recrutement IDF

Titre

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)

Type

Interventional

Pathologie

Métastase tumorale
Tumeurs

Phase

Phase 1/Phase 2

Promoteur

Nuvalent Inc. (Voir sur ClinicalTrials)

Date de début

juin 2022

Date de fin

janvier 2028

Dernière mise à jour

08 novembre 2026

Résumé

Phase 1/2, dose escalation and expansion study designed to evaluate the safety and tolerability of neladalkib (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 neladalkib and will determine the RP2D and, if applicable, the maximum tolerated dose (MTD) of neladalkib 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 neladalkib 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 neladalkib in patients with advanced ALK-positive NSCLC and other solid tumors. A drug-drug interaction (DDI) sub-study will determine the effect of neladalkib on the pharmacokinetics of midazolam and repaglinide, as well as the effect of itraconazole on the pharmacokinetics of neladalkib, in patients with advanced ALK-positive NSCLC

Détail

Voir le détail 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. In the DDI sub-study, study patients will be enrolled into 2 distinct cohorts: - Cohort G (DDI sub-study with midazolam and repaglinide): Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI. - Cohort H (DDI sub-study with itraconazole): Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI. Fermer le détail

Etablissements

Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données
CLCC INSTITUT GUSTAVE ROUSSY	Benjamin BESSE	En recrutement IDF	10/11/2026 15:45:04	Contacter

Critères

Genre

Tous

Nombre d'inclusion

Critère d'inclusion

1. Age ≥18 years, Phase 2 Cohort 2f only: Age ≥12 years and weighing >40 kg. DDI
sub-study Cohorts G and H only: age 18-60 years, inclusive

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. DDI sub-study cohorts: Histologically or cytologically confirmed locally advanced or
metastatic NSCLC with a documented ALK rearrangement

5. DDI sub-study cohorts: Must have previously received ≥1 ALK TKI; no prior
investigational agents targeting ALK; any number of prior chemotherapy and/or
immunotherapy

6. 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

7. Adequate organ function and bone marrow reserve

Exclusion criteria:

Critère de non inclusion

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.

NCT05384626 - 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)

Informations générales
Etablissements
Critères
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