OverviewStudy detailsEligibilityThings to knowResearchStudy plan
info
Simplify with AI

A Study of NVL-330 in Patients With Advanced or Metastatic HER2-altered NSCLC (HEROEX-1)

PHASE1RECRUITING

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.

Study details:

The planned Phase 1a/1b first-in-human study is designed as a two-part clinical trial to investigate NVL-330 in pre-treated patients with advanced or metastatic HER2-altered NSCLC. The dose escalation phase of the trial is designed to enroll a set number of patients per cohort at protocol defined dose levels. After the initial patients 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).

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Age ≥ 18 years
  2. Histologically or cytologically confirmed locally advanced or metastatic NSCLC
  3. Documented HER2 status as follows: 1. Phase 1a: Documented oncogenic HER2 mutation such as HER2 exon20 insertion mutations or single nucleotide variants or HER2 amplification. 2. Phase 1b: Documented oncogenic HER2 mutation.
  4. Identification of lesions as follows: 1. Phase 1a: Must have evaluable disease (target or nontarget) according to RECIST 1.1. 2. Phase 1b: Must have measurable disease, defined as ≥ 1 radiologically measurable target lesion according to RECIST 1.1.
  5. Adequate organ function and bone marrow reserve

Exclusion criteria

  1. Patient's cancer has known oncogenic driver alteration other than HER2
  2. Known allergy/hypersensitivity to excipients of NVL-330
  3. Major surgery within 4 weeks of the first dose of study drug
  4. Ongoing or recent anticancer therapy
  5. Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE1

trial

Study ID

NCT06521554

Intervention or treatment

DRUG: NVL-330

Conditions

  • Locally Advanced Solid Tumor
  • Metastatic Solid Tumor

  • Condition: Locally Advanced Solid Tumor, Metastatic Solid Tumor

  • DRUG: NVL-330

  • Camperdown, New South Wales, Australia and more

  • Sponsor: Nuvalent Inc.

Save

Share

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Chris O'Brien Lifehouse

Select from list below to view details:

  • Chris O'Brien Lifehouse

    Camperdown, New South Wales, Australia

  • North Shore Health Hub

    Saint Leonards, New South Wales, Australia

Loading map...

Who is running the clinical trial?

NI

Nuvalent Inc.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Phase 1a dose escalation
  • NVL-330 oral daily dosing
Drug: NVL-330
    EXPERIMENTAL: Phase 1b dose expansion
    • NVL-330 oral daily dosing
    Drug: NVL-330

      What is the study measuring?

      Primary Outcome

      MeasureDescriptionTime Frame
      Recommended Phase 2 Dose (RP2D)To determine up to 2 RP2D CandidatesAs determined by incidence of DLTs during the first 28 days of treatment (ie, Cycle 1)
      Maximum Tolerated Dose (MTD)If applicable, to determine the MTDAs 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, v5.0First dose of study drug through 30 days after the last dose of study drug

      Secondary Outcome

      MeasureDescriptionTime Frame
      Effect of Food on Maximum Plasma Concentration (Cmax) of NVL-330To determine the effect of food on maximum plasma concentration (Cmax) of NVL-330Pre-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-330To determine the effect of food on area under the curve from time 0 to 24 of NVL-330Pre-dose and up to 24 hours post-dose
      Effect of Food on Area Under the Curve from Time 0 to Infinity (AUCinf) of NVL-330To determine the effect of food on area under the curve from time 0 to infinity of NVL-330Pre-dose and up to 24 hours post-dose
      Effect of Food on Time of Maximum Concentration (Tmax) of NVL-330To determine the effect of food on time of maximum concentration of NVL-330Pre-dose and up to 24 hours post-dose
      Maximum plasma concentration (Cmax) of NVL-330To determine the maximum plasma concentration (Cmax) of NVL-330Pre-dose and up to 24 hours post-dose
      Maximum plasma concentration (Cmax- dose normalized) of NVL-330To determine the maximum plasma concentration (Cmax-dose normalized) of NVL-330Pre-dose and up to 24 hours post-dose
      Plasma concentration at the end of the dosing interval (Ctau) of NVL-330To determine the plasma concentration at the end of the dosing interval (Ctau) of NVL-330Pre-dose and up to 24 hours post-dose
      Plasma concentration 24 hours post-dose (C24) of NVL-330To determine the plasma concentration 24 hours post-dose (C24) of NVL-330Pre-dose and up to 24 hours post-dose
      Average plasma concentration (Cavg) of NVL-330To determine the average plasma concentration (Cavg) of NVL-330Pre-dose and up to 24 hours post-dose
      Time of maximum concentration (Tmax) of NVL-330To determine the time of maximum concentration (Tmax) of NVL-330Pre-dose and up to 24 hours post-dose
      Area Under the Curve at the End of the Dosing Interval (AUCtau) of NVL-330To determine the area under the curve at the end of the dosing interval (AUCtau) of NVL-330Pre-dose and up to 24 hours post-dose
      Area Under the Curve at the End of the Dosing Interval (AUCtau - dose normalized) of NVL-330To determine the area under the curve at the end of the dosing interval (AUCtau - dose normalized) of NVL-330Pre-dose and up to 24 hours post-dose
      Area Under the Curve From Time 0 to 24 (AUC0-24) of NVL-330To determine the area under the curve from time 0 to 24 (AUC0-24) of NVL-330Pre-dose and up to 24 hours post-dose
      Area Under the Curve From Time 0 to 24 (AUC0-24 - dose normalized) of NVL-330To determine the area under the curve from time 0 to 24 (AUC0-24 - dose normalized) of NVL-330Pre-dose and up to 24 hours post-dose
      Area Under the Curve From Time 0 to Infinity (AUCinf) of NVL-330To determine the area under the curve from time 0 to infinity (AUCinf) of NVL-330Pre-dose and up to 24 hours post-dose
      Area Under the Curve From Time 0 to Infinity (AUCinf - dose normalized) of NVL-330To determine the area under the curve from time 0 to infinity (AUCinf - dose normalized) of NVL-330Pre-dose and up to 24 hours post-dose
      Oral clearance (CL/F) of NVL-330To determine the oral clearance (CL/F) of NVL-330Pre-dose and up to 24 hours post-dose
      Volume of Distribution (Vz/F) of NVL-330To determine the volume of distribution (Vz/F) of NVL-330Pre-dose and up to 24 hours post-dose
      Accumulation Ratio of NVL-330To determine the ratio of accumulation of NVL-330Pre-dose and up to 24 hours post-dose
      Half-life (t1/2) of NVL-330To determine the half-life (t1/2) of NVL-330Pre-dose and up to 24 hours post-dose
      Objective Response Rate (ORR)Objective Response Rate (ORR) as determined by RECIST 1.1 criteria2 -3 years after first patient dosed
      Duration of Response (DOR)Time from first investigator-assessed response to radiographic disease progression or death2 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 death2 to 3 years after first patient dosed
      Time to Response (TTR)The time from first dose to first confirmed radiographic responseApproximately 3 years
      Are you running this trial?If you're a clinic or sponsor, you can claim this study.
      Claim this trial

      References

      Clinical Trials Gov: A Study of NVL-330 in Patients With Advanced or Metastatic HER2-altered NSCLC (HEROEX-1)

      Other trials to consider

      Loading suggested trials...

      Top searched conditions

      Breast CancerLung CancerType 2 DiabetesDermatitisAlzheimersParkinsonsLupusCrohn’s DiseaseAsthmaHypertensionCOPDMultiple SclerosisOsteoarthritisHIV/AIDSPsoriasisStrokeObesityProstate CancerDepressionCardiovascular