Testing the Addition of an Anti-Cancer Drug, Daraxonrasib, for Relapsed or Refractory Solid Tumors With RAS Mutations

NCT07819838 | Not Yet Recruiting Phase 1 FDA Drug

• 3 other identifiers: PEPN2611NCI-2026-06456UM1CA228823
• Study Type: interventional
• Target: 77
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase I/II trial tests the safety, side effects, best dose and how well giving daraxonrasib works for the treatment of pediatric patients with solid tumors with RAS mutations that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Daraxonrasib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving daraxonrasib may be safe, tolerable and/or effective in treating patients with relapsed or refractory solid tumors with RAS mutations.

Conditions

Recurrent Childhood Neuroblastoma; Recurrent Childhood Rhabdomyosarcoma; Refractory Childhood Neuroblastoma; Refractory Childhood Rhabdomyosarcoma; Recurrent Childhood Malignant Solid Neoplasm; Refractory Childhood Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD) (Phase 1 part A)

  MTD defined as the maximum dose at which fewer than one-third of patients experience dose limiting toxicity during cycle 1 of therapy.

  Up to completion of cycle 1 (cycle length = 21 days)

• Incidence of adverse events (Phase 1 and 2, parts A and B)

  Toxicities for patients will be described separately. Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.

  Up to 5 years

• Best response of disease (Phase 2 dose expansion [part B])

  Disease response will be assessed according to Response Evaluation Criteira in Solid Tumors (RECIST) criteria for patients with solid tumors (International Neuroblastoma Response Criteria \[INRC\] for patients with neuroblastoma), and will be reported descriptively.

  Up to 5 years

Secondary Outcomes (7)

• Best response of disease (Phase 1, part A)

  Up to 5 years

• Best response of disease (Phase 1, part B)

  Up to 5 years

• Pharmacokinetics (Phase 1 dose escalation and phase 2 dose expansion [parts A and B])

  At cycle 1 day 1 (predose, 30 minutes, 2 hours, 4.5 hours, 7 hours post dose), cycle 1 day 15 predose, cycle 2 day 1 (cycle length = 21 days)

• Progression free survival

  Up to 5 years

• Overall survival

  Up to 5 years

Other Outcomes (2)

• Frequency of detectable RAS mutations by circulating tumor deoxyribonucleic acid (ctDNA)

  At cycle 1 day 1 (pre-dose), cycle 1 day 8, cycle 2 day 1, cycle 2 days 21 and end of treatment (cycle length = 21 days)

• Mutant allele fraction in ctDNA

  At cycle 1 day 1 (pre-dose), cycle 1 day 8, cycle 2 day 1, cycle 2 days 21 and end of treatment (cycle length = 21 days)

Study Arms (1)

Treatment (daraxonrasib)

EXPERIMENTAL

Patients receive daraxonrasib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 28 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo urine sample collection during screening and undergo x-ray imaging, diagnostic imaging and blood sample collection throughout the study. Patients may also undergo bone marrow aspiration and biopsy throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Daraxonrasib; Procedure: Diagnostic Imaging Testing; Procedure: X-Ray Imaging

Interventions

Biospecimen Collection PROCEDURE

Undergo blood and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (daraxonrasib)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (daraxonrasib)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (daraxonrasib)

Daraxonrasib DRUG

Given PO

Also known as: RAS Inhibitor RMC-6236, Ras-selective Tri-complex Inhibitor RMC-6236, RASMUTLI(ON) Inhibitor RMC-6236, Rasonque, RMC 6236, RMC-6236, RMC6236

Treatment (daraxonrasib)

Diagnostic Imaging Testing PROCEDURE

Undergo diagnostic imaging

Also known as: Diagnostic Imaging, Medical Imaging

Treatment (daraxonrasib)

X-Ray Imaging PROCEDURE

Undergo x-ray imaging

Also known as: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs, Radiographic Imaging, Radiographic imaging procedure (procedure), Radiography, RG, Static X-Ray, X-Ray

Treatment (daraxonrasib)

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• PARTS A1 AND B: Patients must be ≥ 2 years and ≤ 17 years of age at the time of study enrollment
• PART A2: Patients must be ≥ 1 year and ≤ 17 years of age at the time of study enrollment
• Patients with recurrent or refractory extracranial solid tumors. Patients must have had histologic verification of malignancy at original diagnosis or relapse
• PARTS A1 AND A2: Patients with relapsed or refractory RAS mutant extracranial solid tumors
• PARTS B1, B2, AND B3: Patients with relapsed or refractory fusion-negative rhabdomyosarcoma (B1: RMS), neuroblastoma (B2: NBL), or other extracranial solid tumors (B3: Other)
• All patients must have a College of American Pathologists (CAP)/Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory report which documents RAS mutation at diagnosis or time of relapse, defined as nonsynonymous mutations in KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61)
• PAST A: Patients must have either measurable or evaluable disease
• PART B: Patients must have International Neuroblastoma Response Criteria (INRC) evaluable (neuroblastoma) or Response Evaluation Criteria in Solid Tumors (RECIST) measurable (all other diagnoses) disease
• NEUROBLASTOMA: Bone marrow aspirates and biopsies are required at baseline for neuroblastoma patients, per INRC guidelines
• SOLID TUMORS: Bone marrow aspirates and biopsies are required at baseline for patients with other solid tumors with a history of bone marrow metastatic disease
• Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• Karnofsky ≥ 50% for patients \>16 year of age and Lansky ≥ 50% for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• See https://www.cogmembers.org/site/pages/default.aspx?page=Prot\_reference\_ materials under Standard References
• Patients must have fully recovered (grade \< 2) from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately.
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See DVL homepage on the Children's Oncology Group (COG) Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.

You may not qualify if:

• Pregnant or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study and for at least one month after the last dose of study treatment for females and one week after the last dose of study treatment for males. Abstinence is an acceptable method of birth control
• Corticosteroids: Patients must be on a stable or decreasing dose of corticosteroids for at least 7 days prior to enrollment. If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
• Anti-GVHD agents post-transplant: Patients must not be receiving tacrolimus or other medications to prevent graft-versus-host disease post bone marrow transplant
• Cyclosporine and derivatives: Patients must not require concomitant treatment with systemically bioavailable cyclosporine A or its derivatives
• CYP3A4 inhibitors/inducers: Moderate or strong systemic CYP3A4 inhibitors or inducers are prohibited during treatment with daraxonrasib. These agents should be discontinued at least 14 days prior to enrollment.
• Local or topical treatments are allowed.
• Seville oranges, grapefruit, and grapefruit products are considered moderate or strong CYP3A4 inhibitors on this protocol
• Patients enrolled on Parts A1 and B must be able to swallow 20 mg and 100 mg tablets intact. Nasogastric or G tube administration is not allowed
• Patients whose tumors harbor a somatic PAX3 or FOXO1 translocation found on deoxyribonucleic acid (DNA), ribonucleic acid (RNA), or fluorescence in situ hybridization (FISH) testing are ineligible
• Patients with primary central nervous system (CNS) tumors or untreated CNS metastases are ineligible.
• Treated CNS metastases are not excluded if stable and asymptomatic.
• All patients with previously treated brain metastases must have a magnetic resonance imaging (MRI), or computed tomography (CT) if MRI is contraindicated, of the brain within 28 days prior enrollment to confirm there has been no disease progression
• Patients with any condition expected to interfere with the absorption of orally administered medications are ineligible
• Patients who have acute coronary syndrome (e.g., unstable angina, myocardial infarction) within 6 months prior to study enrollment

Sponsors & Collaborators

• Children's Oncology Group: lead

MeSH Terms

Interventions

Specimen Handling; Biopsy; X-Rays; Phantoms, Imaging

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Equipment and Supplies

Study Officials

• Amit J Sabnis

  Pediatric Early Phase Clinical Trial Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2026
• First Posted: September 15, 2026
• Study Start (Estimated): April 9, 2027
• Primary Completion (Estimated): April 9, 2032
• Study Completion (Estimated): April 9, 2032
• Last Updated: September 15, 2026

Record last verified: 2026-09