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A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)

ConditionsLocally Advanced Solid TumorMetastatic Solid Tumor
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age12+
SponsorNuvalent Inc.

About this trial

Phase 1/2, dose escalation and expansion study designed to evaluate the safety and tolerability of neladalkib (NVL-655), determine the recommended phase 2 dose (RP2D), and evaluate the antitumor activity in patients with advanced ALK- positive (ALK+) NSCLC and other solid tumors.

Phase 1 will evaluate the overall safety and tolerability of neladalkib and will determine the RP2D and, if applicable, the maximum tolerated dose (MTD) of neladalkib in patients with advanced ALK+ solid tumors.

Phase 2 will determine the objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR) of neladalkib at the RP2D. Secondary objectives will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and clinical benefit rate (CBR) of neladalkib in patients with advanced ALK-positive NSCLC and other solid tumors.

A drug-drug interaction (DDI) sub-study will determine the effect of neladalkib on the pharmacokinetics of midazolam and repaglinide, as well as the effect of itraconazole on the pharmacokinetics of neladalkib, in patients with advanced ALK-positive NSCLC

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥18 years, Phase 2 Cohort 2f only: Age ≥12 years and weighing >40 kg. DDI sub-study Cohorts G and H only: age 18-60 years, inclusive

Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation.

Phase 2

Phase 2 Cohorts except 2f: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with a documented ALK rearrangement

Disqualifiers

Patient's cancer has a known oncogenic driver alteration other than ALK.

Known allergy/hypersensitivity to excipients of NVL-655.

Major surgery within 4 weeks of the study entry

Ongoing or anticancer therapy

Trial design

Design model

Sequential

Treatments tested in this trial

  • Neladalkib (NVL-655)

    Drug

    Oral Tablet of Neladalkib (NVL-655)

  • Midazolam

    Drug

    Oral Solution of Midazolam

  • Repaglinide

    Drug

    Oral Tablet of Repaglinide

  • Itraconazole

    Drug

    Oral Solution of Itraconazole

Treatment groups

840 Participants
are divided into 9 treatment groups

9

Treatment groups

See each treatment group below.

Group A: Phase 1 dose escalationExperimental treatment 1 intervention
Group B: Cohort 2aExperimental treatment 1 intervention
Group C: Cohort 2bExperimental treatment 1 intervention
Group D: Cohort 2cExperimental treatment 1 intervention
Group E: Cohort 2dExperimental treatment 1 intervention
Group F: Cohort 2eExperimental treatment 1 intervention
Group G: Cohort 2fExperimental treatment 1 intervention
Group H: Cohort G (DDI sub-study)Experimental treatment 3 interventions
Group I: Cohort H (DDI sub-study)Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Dose limiting toxicities (DLTs) (Phase 1)

Define the dose limiting toxicities (DLTs)

Time frame
Within the first 21 days of the first neladalkib (NVL-655) dose
2

Recommended Phase 2 Dose (RP2D) (Phase 1)

To determine the RP2D

Time frame
Within 21 days of last patient dosed during escalation
3

Objective Response Rate (ORR) (Phase 2)

To determine ORR as assessed by BICR

Time frame
2-3 years after first patient dosed.
4

Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 1)

Incidence and severity of treatment-emergent adverse events (TEAEs)

Time frame
Approximately 3 years

Secondary outcomes

1

Maximum plasma concentration, (Cmax) of neladalkib (NVL-655)

To determine the maximum plasma concentration (Cmax) of neladalkib (NVL-655)

Time frame
Pre-dose and up to 24 hours post-dose
2

Plasma concentration at the end of the dosing interval (Ctau) of neladalkib (NVL-655)

To determine the plasma concentration at the end of the dosing interval (Ctau) of neladalkib (NVL-655)

Time frame
Pre-dose and up to 24 hours post-dose
3

Average plasma concentration (Cavg) of neladalkib (NVL-655)

To determine the average plasma concentration (Cavg) of neladalkib (NVL-655)

Time frame
Pre-dose and up to 24 hours post-dose
4

Time of maximum concentration (Tmax) of neladalkib (NVL-655)

To determine the time of maximum concentration (Tmax) of neladalkib (NVL-655)

Time frame
Pre-dose and up to 24 hours post-dose

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Nuvalent Inc.

Lead sponsor

Source ClinicalTrials.gov
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