Overview Study details Eligibility Things to know Research Study plan

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Overview Study details Eligibility Things to know Research Study plan

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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)

PHASE1PHASE2RECRUITING

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.

Study details:

In Phase 2, study patients will be enrolled into 6 distinct cohorts:. * Cohort 2a: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received 1 prior 2nd-generation ALK TKI (ceritinib, alectinib, or brigatinib). Up to 2 prior lines of chemotherapy and/or immunotherapy are allowed.

* Cohort 2b: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received 2-3 prior ALK TKIs (crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib). Up to 2 prior lines of chemotherapy and/or immunotherapy are allowed. * Cohort 2c: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received lorlatinib as the only prior ALK TKI therapy.

Up to one prior line of chemotherapy and/or immunotherapy received prior to lorlatinib is allowed. * Cohort 2d: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who are naïve to ALK TKI therapy. Up to one prior line of chemotherapy and/or immunotherapy is allowed.

* Cohort 2e: Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts. * Cohort 2f: Patients with other solid tumors harboring an ALK rearrangement or activating ALK mutation, who have received ≥1 prior systemic anticancer therapy, or for whom no satisfactory standard therapy exists.

Eligibility criteria

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

Inclusion criteria

Age ≥18 years, Phase 2 Cohort 2f only: Age ≥12 years and weighing >40 kg.
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.
Phase 2 Cohort 2f: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented ALK rearrangement or activating ALK mutation detected by certified assay.
Phase 1: Must have evaluable disease (target or nontarget) according to RECIST 1.1 Phase 2: Must have measurable disease according to RECIST 1.1.
Adequate organ function and bone marrow reserve.

Exclusion criteria

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.
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

TREATMENT

Phase

PHASE1PHASE2

Study ID

NCT05384626

Intervention or treatment

DRUG: Neladalkib (NVL-655)

Conditions

Locally Advanced Solid Tumor
Metastatic Solid Tumor

Condition: Locally Advanced Solid Tumor, Metastatic Solid Tumor
DRUG: Neladalkib (NVL-655)
Sydney, New South Wales, Australia and more
Sponsor: Nuvalent Inc.

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Research sites nearby

Closest Location:

Royal North Shore Hospital

Select from list below to view details:

Royal North Shore Hospital
Sydney, New South Wales, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia

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Who is running the clinical trial?

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/Arm	Intervention/Treatment
EXPERIMENTAL: Phase 1 dose escalation Neladalkib (NVL-655) oral daily dosing	Drug: Neladalkib (NVL-655)
EXPERIMENTAL: Cohort 2a Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received 1 prior 2nd-generation ALK TKI (ceritinib, alectinib, or brigatinib). Up to 2 prior lines of chemotherapy and/or immunotherapy are allowed.	Drug: Neladalkib (NVL-655)
EXPERIMENTAL: Cohort 2b Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received 2-3 prior ALK TKIs (crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib). Up to 2 prior lines of chemotherapy and/or immunotherapy are allowed.	Drug: Neladalkib (NVL-655)
EXPERIMENTAL: Cohort 2c Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who have received lorlatinib as the only prior ALK TKI therapy. Up to one prior line of chemotherapy and/or immunotherapy received prior to lorlatinib is allowed.	Drug: Neladalkib (NVL-655)
EXPERIMENTAL: Cohort 2d Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, who are naïve to ALK TKI therapy. Up to one prior line of chemotherapy and/or immunotherapy is allowed.	Drug: Neladalkib (NVL-655)
EXPERIMENTAL: Cohort 2e Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts.	Drug: Neladalkib (NVL-655)
EXPERIMENTAL: Cohort 2f Patients with other solid tumors harboring an ALK rearrangement or activating ALK mutation, who have received ≥1 prior systemic anticancer therapy, or for whom no satisfactory standard therapy exists.	Drug: Neladalkib (NVL-655)
EXPERIMENTAL: Cohort G (DDI sub-study) Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI	Drug: Neladalkib (NVL-655), Drug: Midazolam, Drug: Repaglinide
EXPERIMENTAL: Cohort H (DDI sub-study) Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI	Drug: Neladalkib (NVL-655), Drug: Itraconazole

What is the study measuring?

Primary Outcome

Measure	Description	Time Frame
Dose limiting toxicities (DLTs) (Phase 1)	Define the dose limiting toxicities (DLTs)	Within the first 21 days of the first neladalkib (NVL-655) dose
Recommended Phase 2 Dose (RP2D) (Phase 1)	To determine the RP2D	Within 21 days of last patient dosed during escalation
Objective Response Rate (ORR) (Phase 2)	To determine ORR as assessed by BICR	2-3 years after first patient dosed.
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)	Approximately 3 years

Secondary Outcome

Measure	Description	Time Frame
Maximum plasma concentration, (Cmax) of neladalkib (NVL-655)	To determine the maximum plasma concentration (Cmax) of neladalkib (NVL-655)	Pre-dose and up to 24 hours post-dose
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)	Pre-dose and up to 24 hours post-dose
Average plasma concentration (Cavg) of neladalkib (NVL-655)	To determine the average plasma concentration (Cavg) of neladalkib (NVL-655)	Pre-dose and up to 24 hours post-dose
Time of maximum concentration (Tmax) of neladalkib (NVL-655)	To determine the time of maximum concentration (Tmax) of neladalkib (NVL-655)	Pre-dose and up to 24 hours post-dose
Area under the curve at the end of the dosing interval (AUCtau) of neladalkib (NVL-655)	To determine the area under the curve at the end of the dosing interval (AUCtau) of neladalkib (NVL-655)	Pre-dose and up to 24 hours post-dose
Area under the curve from time 0 to 24 (AUC0-24) of neladalkib (NVL-655)	To determine the area under the curve from time 0 to 24 (AUC0-24) of neladalkib (NVL-655)	Pre-dose and up to 24 hours post-dose
Area under the curve from time 0 to infinity (AUCinf) of neladalkib (NVL-655)	To determine the area under the curve from time 0 to infinity (AUCinf) of neladalkib (NVL-655)	Pre-dose and up to 24 hours post-dose
Oral clearance (CL/F) of neladalkib (NVL-655)	To determine the oral clearance (CL/F) of neladalkib (NVL-655)	Pre-dose and up to 24 hours post-dose
Volume of distribution (Vz/F) of neladalkib (NVL-655)	To determine the volume of distribution (Vz/F) of neladalkib (NVL-655)	Pre-dose and up to 24 hours post-dose
Half-life (t1/2) of neladalkib (NVL-655)	To determine the half-life (t1/2) of neladalkib (NVL-655)	Pre-dose and up to 24 hours post-dose
Objective response rate (ORR) (Phase 1)	Determine ORR as assessed by Investigator	2-3 years after first patient dosed
Duration of response (DOR)	Determine DOR of neladalkib (NVL-655) until radiographic disease progression or death	2-3 years after first patient dosed
Clinical benefit rate (CBR)	Determine CBR of neladalkib (NVL-655)	2-3 years after first patient dosed
Time to response	Determine time to response of neladalkib (NVL-655)	Approximately 3 years
Progression-free survival (PFS)	Determine PFS of neladalkib (NVL-655) until radiographic disease progression or death	2-3 years after first patient dosed
Overall survival (OS) (Phase 2)	Determine OS	Approximately 3 years
Number of participants with treatment-emergent adverse events, as assessed by CTCAE, V5.0 (Phase 2)	Incidence and severity of treatment-emergent adverse events (TEAEs)	Approximately 3 years
Quality of life assessment	Measure the quality of life in patients with cancer and/or lung cancer.	2-3 years after first patient dosed

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References

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

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