A Study of NVL-330 in Patients With Advanced or Metastatic HER2-altered NSCLC (HEROEX-1)
NCT Number: NCT06521554
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Locally Advanced Solid Tumor|Metastatic Solid Tumor
Interventions: DRUG: NVL-330
Sponsor: Nuvalent Inc.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 120
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-18
Completion Date: 2026-03
Locations: Sarah Cannon Research Institute at HealthONE, Denver, Colorado, 80218, United States|Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States|SCRI Oncology Partners, Nashville, Tennessee, 37203, United States|NEXT Virginia, Fairfax, Virginia, 22031, United States

Summary:
Phase 1a/1b dose escalation and expansion study designed to evaluate the safety and tolerability of NVL-330, determine the recommended Phase 2 dose (RP2D), and evaluate the antitumor activity in patients with advanced or metastatic HER2-altered NSCLC.

Phase 1a dose escalation is designed to assess the safety and tolerability of NVL-330 and to select the candidate RP2D(s) and, if applicable, the MTD.

Phase 1b expansion is designed to further evaluate the overall safety and tolerability of the candidate RP2D(s) of NVL-330 and to determine the RP2D of NVL 330 in patients with advanced or metastatic HER2 mutant NSCLC.

Primary Outcome Measures: Recommended Phase 2 Dose (RP2D), To determine up to 2 RP2D Candidates, As determined by incidence of DLTs during the first 28 days of treatment (ie, Cycle 1)|Maximum Tolerated Dose (MTD), If applicable, to determine the MTD, As determined by incidence of DLTs during the first 28 days of treatment (ie, Cycle 1)|Incidence and severity of Treatment Emergent Adverse Events (TEAEs), Number of participants with TEAEs as assessed by CTCAE, v5.0, First dose of study drug through 30 days after the last dose of study drug
Secondary Outcome Measures: Effect of Food on Maximum Plasma Concentration (Cmax) of NVL-330, To determine the effect of food on maximum plasma concentration (Cmax) of NVL-330, Pre-dose and up to 24 hours post-dose|Effect of Food on Area Under the Curve from Time 0 to 24 (AUC0-24) of NVL-330, To determine the effect of food on area under the curve from time 0 to 24 of NVL-330, Pre-dose and up to 24 hours post-dose|Effect of Food on Area Under the Curve from Time 0 to Infinity (AUCinf) of NVL-330, To determine the effect of food on area under the curve from time 0 to infinity of NVL-330, Pre-dose and up to 24 hours post-dose|Effect of Food on Time of Maximum Concentration (Tmax) of NVL-330, To determine the effect of food on time of maximum concentration of NVL-330, Pre-dose and up to 24 hours post-dose|Maximum plasma concentration (Cmax) of NVL-330, To determine the maximum plasma concentration (Cmax) of NVL-330, Pre-dose and up to 24 hours post-dose|Maximum plasma concentration (Cmax- dose normalized) of NVL-330, To determine the maximum plasma concentration (Cmax-dose normalized) of NVL-330, Pre-dose and up to 24 hours post-dose|Plasma concentration at the end of the dosing interval (Ctau) of NVL-330, To determine the plasma concentration at the end of the dosing interval (Ctau) of NVL-330, Pre-dose and up to 24 hours post-dose|Plasma concentration 24 hours post-dose (C24) of NVL-330, To determine the plasma concentration 24 hours post-dose (C24) of NVL-330, Pre-dose and up to 24 hours post-dose|Average plasma concentration (Cavg) of NVL-330, To determine the average plasma concentration (Cavg) of NVL-330, Pre-dose and up to 24 hours post-dose|Time of maximum concentration (Tmax) of NVL-330, To determine the time of maximum concentration (Tmax) of NVL-330, Pre-dose and up to 24 hours post-dose|Area Under the Curve at the End of the Dosing Interval (AUCtau) of NVL-330, To determine the area under the curve at the end of the dosing interval (AUCtau) of NVL-330, Pre-dose and up to 24 hours post-dose|Area Under the Curve at the End of the Dosing Interval (AUCtau - dose normalized) of NVL-330, To determine the area under the curve at the end of the dosing interval (AUCtau - dose normalized) of NVL-330, Pre-dose and up to 24 hours post-dose|Area Under the Curve From Time 0 to 24 (AUC0-24) of NVL-330, To determine the area under the curve from time 0 to 24 (AUC0-24) of NVL-330, Pre-dose and up to 24 hours post-dose|Area Under the Curve From Time 0 to 24 (AUC0-24 - dose normalized) of NVL-330, To determine the area under the curve from time 0 to 24 (AUC0-24 - dose normalized) of NVL-330, Pre-dose and up to 24 hours post-dose|Area Under the Curve From Time 0 to Infinity (AUCinf) of NVL-330, To determine the area under the curve from time 0 to infinity (AUCinf) of NVL-330, Pre-dose and up to 24 hours post-dose|Area Under the Curve From Time 0 to Infinity (AUCinf - dose normalized) of NVL-330, To determine the area under the curve from time 0 to infinity (AUCinf - dose normalized) of NVL-330, Pre-dose and up to 24 hours post-dose|Oral clearance (CL/F) of NVL-330, To determine the oral clearance (CL/F) of NVL-330, Pre-dose and up to 24 hours post-dose|Volume of Distribution (Vz/F) of NVL-330, To determine the volume of distribution (Vz/F) of NVL-330, Pre-dose and up to 24 hours post-dose|Accumulation Ratio of NVL-330, To determine the ratio of accumulation of NVL-330, Pre-dose and up to 24 hours post-dose|Half-life (t1/2) of NVL-330, To determine the half-life (t1/2) of NVL-330, Pre-dose and up to 24 hours post-dose|Objective Response Rate (ORR), Objective Response Rate (ORR) as determined by RECIST 1.1 criteria, 2 -3 years after first patient dosed|Duration of Response (DOR), Time from first investigator-assessed response to radiographic disease progression or death, 2 to 3 years after first patient dosed|Intracranial Objective Response Rate (IC-ORR), The proportion of patients with a confirmed intracranial response (IC-CR or IC-PR), 2 to 3 years after first patient dosed|Intracranial Duration of Response (IC-DOR), The time from first investigator-assessed intracranial response to radiographic intracranial disease progression or death, 2 to 3 years after first patient dosed|Time to Response (TTR), The time from first dose to first confirmed radiographic response, Approximately 3 years