A Study of NVL-655 in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)

JRCT ID: jRCT2031240335

Registered date:17/09/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Advanced NSCLC and Other Solid Tumors
• Date of first enrollment: 17/09/2024
• Target sample size: 18
• Countries of recruitment: USA,Japan,UK,Japan,Italy,Japan,Australia,Japan,Belgium,Japan,Canada,Japan,France,Japan,Netherlands,Japan,Spain,Japan,Germany,Japan,Taiwan,Japan,Singapore,Japan,Korea,Japan,Switzerland,Japan
• Study type: Interventional

Intervention(s)

IMP: NVL-655
NVL-655 is a tablet taken by mouth.
Patients will receive study drug continuously from first dose until disease progression, unacceptable toxicity, withdrawal by patient, or Investigator's decision.
Patients who are deriving clinical benefit in the opinion of the Investigator may continue to receive NVL-655 following disease progression at the discretion of the Investigator in consultation with the Sponsor.

Outcome(s)

Primary Outcome

Dose limiting toxicities (DLTs) (Phase 1): Define the dose limiting toxicities (DLTs)
Recommended Phase 2 Dose (RP2D) (Phase 1): To determine the RP2D
Objective Response Rate (ORR) (Phase 2): To determine ORR as assessed by BICR
Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 1): Incidence and severity of treatment-emergent adverse events (TEAEs)

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

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 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.
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
Prior therapy requirements
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 naive 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.
Inclusion Criteria #3-h: J-SLIC: Patients with ALK fusion-positive NSCLC:>=1 prior ALK TKI therapy, which must include a 2nd or 3rd generation TKI (ceritinib, alectinib, brigatinib, or lorlatinib), and up to 2 prior lines of chemotherapy and/or immunotherapy are allowed.
Patients with other ALK-positive solid tumors: Must be refractory or intolerant to the standard of care.

Exclude 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.

Related Information

• Primary Sponsor: Zhu Viola