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

Nuvalent

Status and phase: Enrolling; Phase 1

Conditions: Locally Advanced Solid Tumor; Metastatic Solid Tumor

Treatments: Drug: NVL-330

Study type: Interventional

Funder types: Industry

Identifiers

NCT06521554

NVL-330-01

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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120 participants in 2 patient groups

Phase 1a dose escalation

Experimental group

Description:

NVL-330 oral daily dosing

Treatment:

Drug: NVL-330

Phase 1b dose expansion

Experimental group

Description:

NVL-330 oral daily dosing

Treatment:

Drug: NVL-330