Ulixertinib in People With Histiocytic Neoplasms

NCT06411821 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 23-282
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 8

Brief Summary

The researchers are doing this study is to find out whether ulixertinib is an effective and safe treatment for people with histiocytic neoplasms.

Conditions

Histiocytic Neoplasms

Keywords

Ulixertinib (BVD-523); 23-282; Mitogen-activated protein kinase

Outcome Measures

Primary Outcomes (1)

• overall response rate

  Best overall response by PET is defined as the best response, according to PRC, recorded from the first day of study treatment until disease progression, recurrence, or death. Complete response Normalization of all lesions' (target and nontarget) SUV to background SUVliver (or SUVbrain for brain lesions) Partial response ≥50% decrease from baseline in sum of SUVs of all target lesions relative to SUVliver (or SUVbrain for brain lesions only) Progressive disease ≥50% increase from nadir in sum of SUV of all target lesions relative to SUVliver (or SUVbrain for brain lesions only), with a minimal absolute increase of 3 units of SUV per target lesion (e.g., SUV 3 to SUV 6) New evaluable lesions deemed to represent unequivocal disease progression\* Stable disease Does not meet other criteria

  1 year

Study Arms (2)

Mitogen-activated protein kinase (MAPK) pathway mutation (primary cohort)

EXPERIMENTAL

Patients in this study will receive ulixertinib, starting at 300 mg twice daily, for every 28-day cycle.

Drug: Ulixertinib

No Mitogen-activated protein kinase (MAPK) pathway mutation identified (exploratory cohort)

EXPERIMENTAL

Patients in this study will receive ulixertinib, starting at 300 mg twice daily, for every 28-day cycle.

Drug: Ulixertinib

Interventions

Ulixertinib DRUG

300 mg twice daily, for every 28-day cycle.

Also known as: BVD-523

Mitogen-activated protein kinase (MAPK) pathway mutation (primary cohort); No Mitogen-activated protein kinase (MAPK) pathway mutation identified (exploratory cohort)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed histiocytic neoplasm or histologic findings consistent with histiocytic neoplasm with confirmatory radiologic or molecular findings. Pathologic examination can be performed at any of the enrolling institutions. This qualification is made because it is well known that biopsies of histiocytic neoplasms are variable and do not always demonstrate "typical" morphologic appearance with all of the classically described elements. As a result, histiocytic neoplasms are not exclusively pathologic diagnoses-rather, they are interpretations of histologic findings in a clinical and radiologic context. These criteria were applied in NCT02649972 and will be applied in this trial
• Identified mutation in MAPK pathway genes, including but not limited to ARAF, BRAF, RAF1, NRAS, KRAS, MAP2K1, MAP2K2, and NF1 (for primary cohort; no mutation needed for exploratory cohort). Tumor mutation may be identified by tumor sequencing or cfDNA-based sequencing. Concordance between cfDNA and tumor sequencing for BRAFV600E and non-BRAF mutations in histiocytic neoplasms has been documented by our group and others
• Measurable disease according to PRC, confirmed by an investigator radiologist
• Age (a) ≥18 years prior to interim safety and efficacy analyses or (b) ≥12 years following the interim safety and efficacy analyses
• The histiocytic neoplasm must be (a) disease that is recurrent/refractory/persistent despite local therapies, chemotherapy, immunosuppression, or BRAF/MEK inhibitors OR (b) multisystem disease OR (c) single-system disease that is causing end-organ dysfunction and is unlikely to benefit from local or conventional (chemotherapy or immunosuppressive) therapies on the basis of evidence-based guidelines (e.g. symptomatic neurologic-only LCH)
• Prior treatment (chemotherapy, immunosuppression, BRAF inhibitor, or MEK inhibitor) is required and the patient must have (a) progressive disease or persistent disease (i.e. having disease measurable by PRC) or (b) intolerance or contraindication to chemotherapy, immunosuppression, BRAF inhibition, or MEK inhibition.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (age ≥ 16) or Lansky 50-100 (age 12-15)
• Adequate renal function (according to the Cockcroft-Gault equation; creatinine ≤1.5 times upper limit of normal \[ULN\] or a glomerular filtration rate of ≥50 mL/min)
• Pediatric patients (\<18 years old) must have a creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m\^2 or serum creatinine based on age/gender as follows:
• \< 13 years- 1.2 (Male),1.2 (Female)
• to \< 16 years- 1.5 (Male), 1.4 (Female)
• °≥ 16 years- 1.7 (Male), 1.4 (Female)
• The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.
• Patients with renal impairment deemed the direct result of disease and therefore amenable to improvement with Ulixertinib treatment may be enrolled at the discretion of the treating investigator
• Adequate hepatic function (total bilirubin ≤1.5 times ULN, aspartate transaminase \[AST\] and- alanine transaminase \[ALT\] ≤3 times ULN or ≤5 times ULN if attributable to liver involvement by tumor). Patients with hepatic impairment deemed the direct result of disease and therefore amenable to improvement with Ulixertinib treatment may be enrolled at the discretion of the treating investigator.

You may not qualify if:

• Uncontrolled or severe intercurrent medical condition
• Receipt of any histiocytic neoplasm-directed therapy (chemotherapy, targeted therapy, biologic) within 28 days or 5 half-lives (whichever is shorter) before the first dose of ulixertinib. Patients previously treated with radiotherapy must have recovered from acute toxicities associated with such treatment
• Histiocytic neoplasm mandated for observation-only or first-line local therapy per established guidelines. Examples would include asymptomatic nodal RDD, asymptomatic osseous ECD, or limited cutaneous LCH
• Major surgery within 4 weeks of the first dose of ulixertinib
• Pregnant, lactating, or breast-feeding (for women)
• Any evidence of serious active infections. Patients are allowed to enroll if they have been fever free for at least 48 h
• History or current evidence of risk of retinal vein occlusion or central serous retinopathy. Examples of risk factors to be considered would include uncontrolled ocular hypertension or history of hyperviscosity.
• Concurrent therapy with drugs known to be strong inhibitors or inducers of CYP1A2, CYP2D6, and CYP3A4
• Concurrent therapy with p-glycoprotein inhibitors and sensitive substrates of CYP1A2, CYP2B6, CYP2C8, and CYP3A4/5 with narrow therapeutic indices
• Inability to swallow oral medications
• Concurrent therapy with any investigational agent
• Any use of an investigational drug within 28 days or 5 half-lives (whichever is shorter). In addition, any drug toxicities should have recovered to grade 1 or less before start of the trial medication

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• BioMed Valley Discoveries, Inc: collaborator

Study Sites (8)

Mayo Clinic (Data Collection Only)

Rochester, Minnesota, 55905, United States

RECRUITING

Memorial Sloan Kettering Basking Ridge (Consent Only)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Consent Only)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk-Commack (Consent Only)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Consent Only)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

ulixertinib

Study Officials

• Eli Diamond, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eli Diamond, MD

CONTACT

212-610-0243; diamone1@mskcc.org

Rona Yaeger, MD

CONTACT

646-888-5109

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter phase 2 trial evaluating the efficacy and safety of monotherapy ulixertinib, an oral selective extracellular signalregulated kinase (ERK) inhibitor, for patients with histiocytic neoplasms:

Study Record Dates

• First Submitted: May 8, 2024
• First Posted: May 13, 2024
• Study Start: May 7, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (8)