Advanced NSCLC and Other Solid Tumors
Conditions
Interventions
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'
Sponsors
Zhu Viola
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion 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.
Exclusion criteria
Exclusion 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) | — |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Japan, Korea, Netherlands, Singapore, Spain, Switzerland, Taiwan, UK, USA
Contacts
Public ContactKazushige Takai
A2 Healthcare Corporation
Outcome results
None listed