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

Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNuvalent Inc.

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥ 18 years

Histologically or cytologically confirmed locally advanced or metastatic NSCLC

Phase 1a: Documented oncogenic HER2 mutation such as HER2 exon20 insertion mutations or single nucleotide variants or HER2 amplification.

Phase 1b: Documented oncogenic HER2 mutation.

Disqualifiers

Participant's cancer has known oncogenic driver alteration other than HER2

Known allergy/hypersensitivity to excipients of NVL-330

Major surgery within 4 weeks of the first dose of study drug

Ongoing or recent anticancer therapy

Trial design

Design model

Sequential

Treatments tested in this trial

  • NVL-330

    Drug

    Oral Tablet of NVL-330

Treatment groups

200 Participants
are divided into 2 treatment groups
Group A: Phase 1a dose escalationExperimental treatment 1 intervention
Group B: Phase 1b dose expansionExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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)
2

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)
3

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

Secondary outcomes

1

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
2

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
3

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
4

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

Other outcomes

Sponsors and contacts

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