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 participants with advanced or metastatic human epidermal growth factor receptor 2 (HER2) -altered non-small lung cancer (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 participants with advanced or metastatic HER2 mutant NSCLC.
The planned Phase 1a/1b first-in-human study is designed as a two-part clinical trial to investigate NVL-330 in pre-treated participants with advanced or metastatic HER2-altered NSCLC. The dose escalation phase of the trial is designed to enroll a set number of participants per cohort at protocol defined dose levels. After the initial participants are treated at a given dose level and monitored for at least 28 days, available data will be reviewed, and initiation of the next dosing group will proceed with consideration given to the overall safety profile. The expansion phase of the trial is designed to further evaluate safety and activity and to confirm the RP2D(s).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
200
Oral Tablet of NVL-330
City of Hope - Lennar
Irvine, California, United States
RECRUITINGUniversity of California, Davis Comprehensive Cancer Center
Sacramento, California, United States
RECRUITINGStanford Cancer Institute
Stanford, California, United States
RECRUITINGSarah Cannon Research Institute at HealthONE
Denver, Colorado, United States
RECRUITINGGeorgetown University Medical Center
Washington D.C., District of Columbia, United States
RECRUITINGSibley Memorial Hospital
Washington D.C., District of Columbia, United States
RECRUITINGSylvester Comprehensive Cancer Center
Miami, Florida, United States
RECRUITINGJohns Hopkins Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Bayview Medical Center
Baltimore, Maryland, United States
RECRUITINGMassachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGHenry Ford Cancer Center
Detroit, Michigan, United States
RECRUITING...and 11 more locations
Recommended Phase 2 Dose (RP2D)
To determine up to 2 RP2D Candidates
Time frame: 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
Time frame: 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
Time frame: First dose of study drug through 30 days after the last dose of study drug
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Pre-dose and up to 24 hours post-dose
Accumulation Ratio of NVL-330
To determine the ratio of accumulation of NVL-330
Time frame: 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
Time frame: Pre-dose and up to 24 hours post-dose
Objective Response Rate (ORR)
Objective Response Rate (ORR) as determined by RECIST 1.1 criteria
Time frame: 2 -3 years after first participant dosed
Duration of Response (DOR)
Time from first investigator-assessed response to radiographic disease progression or death
Time frame: 2 to 3 years after first participant dosed
Intracranial Objective Response Rate (IC-ORR)
The proportion of participants with a confirmed intracranial response (IC-CR or IC-PR)
Time frame: 2 to 3 years after first participant dosed
Intracranial Duration of Response (IC-DOR)
The time from first investigator-assessed intracranial response to radiographic intracranial disease progression or death
Time frame: 2 to 3 years after first participant dosed
Time to Response (TTR)
The time from first dose to first confirmed radiographic response
Time frame: Approximately 3 years
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