A Phase 1/2 interventional study of Neladalkib (NVL-655) and Midazolam in Locally Advanced Solid Tumor and Metastatic Solid Tumor, sponsored by Nuvalent Inc.. Recruiting at 74 sites in 15 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2026-11-06.
Sponsored by Nuvalent Inc. · Phase 1/2, Interventional, and Treatment
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
In Phase 2, study patients will be enrolled into 6 distinct cohorts:
In the DDI sub-study, study patients will be enrolled into 2 distinct cohorts:
4,040 studies on the registry are indexed under Neoplasm Metastasis; 886 are open to participants now.
This study's planned enrollment of 840 is above the median of 50 across 3,268 interventional studies indexed under Neoplasm Metastasis.
Browse Neoplasm Metastasis studies →Nuvalent Inc. is the lead sponsor of 6 studies on the registry; 6 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Phase 2
Exclusion criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Neladalkib (NVL-655) oral daily dosing
Drug: Neladalkib (NVL-655)
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)
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)
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)
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)
Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement, not eligible for other Phase 2 cohorts.
Drug: Neladalkib (NVL-655)
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)
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
Patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement who have received ≥1 prior ALK TKI
Drug: Neladalkib (NVL-655) · Drug: Itraconazole
Oral Tablet of Neladalkib (NVL-655)
Oral Solution of Midazolam
Oral Tablet of Repaglinide
Oral Solution of Itraconazole
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
Recommended Phase 2 Dose (RP2D) (Phase 1)
To determine the RP2D
Time frame: Within 21 days of last patient dosed during escalation
Objective Response Rate (ORR) (Phase 2)
To determine ORR as assessed by BICR
Time frame: 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)
Time frame: Approximately 3 years
Area under the curve of repaglinide (Phase 2 DDI sub-study)
To determine the effect of multiple oral doses of neladalkib (NVL-655) on the PK of a single oral dose of repaglinide
Time frame: Pre-dose and up to 24 hours post-dose
Area under the curve of midazolam (Phase 2 DDI sub-study)
To determine the effect of multiple oral doses of neladalkib (NVL-655) on the PK of a single oral dose of midazolam
Time frame: Pre-dose and up to 24 hours post-dose
Area under the curve of neladalkib (NVL-655) (Phase 2 DDI sub-study)
To determine the effect of itraconazole on the single oral dose PK of neladalkib (NVL-655)
Time frame: Pre-dose and up to 24 hours post-dose
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
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
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
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
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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: Pre-dose and up to 24 hours post-dose
Objective response rate (ORR) (Phase 1)
Determine ORR as assessed by Investigator
Time frame: 2-3 years after first patient dosed
Duration of response (DOR)
Determine DOR of neladalkib (NVL-655) until radiographic disease progression or death
Time frame: 2-3 years after first patient dosed
Clinical benefit rate (CBR)
Determine CBR of neladalkib (NVL-655)
Time frame: 2-3 years after first patient dosed
Time to response
Determine time to response of neladalkib (NVL-655)
Time frame: Approximately 3 years
Progression-free survival (PFS)
Determine PFS of neladalkib (NVL-655) until radiographic disease progression or death
Time frame: 2-3 years after first patient dosed
Overall survival (OS) (Phase 2)
Determine OS
Time frame: 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)
Time frame: Approximately 3 years
Quality of life assessment
Measure the quality of life in patients with cancer and/or lung cancer.
Time frame: 2-3 years after first patient dosed
Incidence and severity of AEs and incidence of abnormalities across laboratory values, ECGs, vital signs, and physical examinations (Phase 2 DDI-sub-study)
Assess the safety and tolerability of neladalkib (NVL-655) when co-administered with repaglinide or midazolam
Time frame: Up to 3 months after last dose
Incidence and severity of AEs and incidence of abnormalities across laboratory values, ECGs, vital signs, and physical examinations (Phase 2 DDI-sub-study)
Assess the safety and tolerability of neladalkib (NVL-655) when co-administered with itraconazole
Time frame: Up to 3 months after last dose
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Started Jun 2022 (actual). Primary completion is estimated for Dec 2027, 66 months after the start.
Of 127 industry-sponsored phase 1/2 interventional studies under Neoplasm Metastasis, half reached primary completion within 56 months of starting (the median), counting those still running; a quarter within 41 and three quarters within 89. This study's planned 66 months is above that.
Counting every sponsor, half of 213 studies reached it within 62 months; a quarter within 41 and three quarters within 89.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Nuvalent Inc.