A Phase 1/2 Study of CBX-12 in Children, Adolescents, or Young Adults With Solid Tumors That Have Come Back After Treatment or Are Difficult to Treat

NCT07830667 | Not Yet Recruiting Phase 1 FDA Drug

• 3 other identifiers: PEPN2612NCI-2026-06652UM1CA228823
• Study Type: interventional
• Target: 79
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase I/II trial tests the safety, best dose, and effectiveness of CBX-12 in the treatment of pediatric patients (ages 12 months to 30 years) with rhabdomyosarcoma, Ewing sarcoma, or other extracranial solid tumors that have come back after a period of improvement (relapsed) or that do not respond to treatment (refractory). CBX-12 is a conjugate drug made of a peptide linked to a drug called exatecan. Upon administration, the peptide portion of CBX-12 gets inserted into the membrane of tumor cells and then exatecan is released into the tumor cells. Exatecan inhibits deoxyribonucleic acid replication in tumors cells, leading to tumor cell death. CBX-12 may be a safe and effective treatment option for pediatric patients with relapsed or refractory rhabdomyosarcoma, Ewing sarcoma, or other solid tumors.

Conditions

Recurrent Childhood Rhabdomyosarcoma; Recurrent Ewing Sarcoma; Recurrent Rhabdomyosarcoma; Refractory Childhood Ewing Sarcoma; Refractory Childhood Malignant Solid Neoplasm; Refractory Childhood Rhabdomyosarcoma; Refractory Ewing Sarcoma; Refractory Rhabdomyosarcoma; Recurrent Childhood Ewing Sarcoma; Recurrent Childhood Malignant Solid Neoplasm; Recurrent Extracranial Malignant Solid Neoplasm; Refractory Extracranial Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (5)

• Maximum tolerated dose (MTD) (part A phase 1 dose escalation)

  The MTD will be defined as the maximum dose level at which fewer than one-third of dose limiting toxicity (DLT)-evaluable patients experience a cycle 1 DLT.

  During cycle 1 of part A (dose escalation phase; cycle length = 21 days)

• Recommended phase 2 dose (part A phase 1 dose escalation)

  During cycle 1 of part A (dose escalation phase; cycle length = 21 days)

• Incidence of adverse events (part A phase 1 dose escalation)

  A descriptive summary of all toxicities will be reported. Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. A patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.

  During cycle 1 of part A (dose escalation phase; cycle length = 21 days)

• Pharmacokinetics (part A phase 1 dose escalation)

  A descriptive analysis of pharmacokinetic parameters will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The pharmacokinetic parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

  During cycle 1 of part A (dose escalation phase; cycle length = 21 days)

• Objective response rate (part B phase 2 dose expansion)

  A responder is defined as a patient who achieves a best confirmed response of partial response or complete response on the study. Response is defined relative to baseline disease. For each disease cohort, response rates will be estimated by the uniformly minimum variance unbiased estimate, p-value, and 93% one-sided confidence interval consistent with a two-stage design.

  Up to 60 months

Secondary Outcomes (1)

• Objective response rate (part A phase 1 dose escalation)

  During part A phase 1 dose escalation

Other Outcomes (4)

• Effect of tumor expression of SLFN11 and/or CAIX on pH low insertion peptide-exatecan conjugate CBX-12 (CBX-12) activity

  Up to 60 months

• Effect of homologous recombinant deficient (HRD) or deoxyribonucleic acid (DNA) repair deficient profile on CBX-12 activity

  Up to 60 months

• Effect of metabolic profile on CBX-12 activity

  Up to 60 months

Study Arms (1)

Treatment (CBX-12)

EXPERIMENTAL

Patients receive CBX-12 IV over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic imaging throughout the study. Patients may undergo collection of bone marrow as clinically indicated and/or optional collection of blood samples on study.

Procedure: Archive Sample Retrieval; Procedure: Biospecimen Collection; Drug: pH Low Insertion Peptide-exatecan Conjugate CBX-12; Procedure: Radiologic Imaging Procedure

Interventions

Archive Sample Retrieval PROCEDURE

Ancillary studies

Also known as: ARCHIVE RETRIEVING

Treatment (CBX-12)

Biospecimen Collection PROCEDURE

Undergo collection of bone marrow and blood samples

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

Treatment (CBX-12)

pH Low Insertion Peptide-exatecan Conjugate CBX-12 DRUG

Given IV

Also known as: Alphalex Conjugate CBX-12, Alphalex-exatecan Conjugate CBX-12, CBX 12, CBX-12, CBX12, Low pH Targeting Alphalex-exatecan Conjugate CBX-12, pHLIP-exatecan Conjugate CBX-12

Treatment (CBX-12)

Radiologic Imaging Procedure PROCEDURE

Undergo radiologic imaging

Treatment (CBX-12)

Eligibility Criteria

• Age: 12 Months - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• PART A: Patients between ≥ 12 months and \< 21 years of age
• PART B: Patients between ≥ 12 months and ≤ 30 years of age
• Patients with recurrent or refractory extracranial solid tumors are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse
• Part A: Patients with relapsed or refractory extracranial solid tumors, excluding central nervous system (CNS)
• Part B: Patients must have relapsed or refractory rhabdomyosarcoma (B1) or Ewing sarcoma (B2)
• PART A: Patients must have either measurable or evaluable disease
• PART B: Patients must have measurable 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
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age
• 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 Developmental Therapeutics (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
• Solid tumor patients: ≥ 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive/anticancer agents on the COG website
• Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): ≥ 7 days after the last dose of agent. See the DVL homepage on the 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.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade ≤ 1
• Corticosteroids: Patients receiving corticosteroids must be on a stable or decreasing dose of corticosteroid 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

You may not qualify if:

• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR 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. Abstinence is an acceptable method of birth control. Women of reproductive potential should use effective contraception and should not breastfeed during treatment and for at least 6 months after the last dose of CBX-12. Male patients treated with CBX-12 should use effective contraception and avoid fathering a child during and up to 4 months after treatment
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 and CYP1A2 (e.g., fluvoxamine) are not eligible. Strong inducers or inhibitors of CYP3A4 and CYP1A2 should be avoided from 14 days prior to enrollment to the end of the study. Enzyme-inducing anticonvulsants: Patients must not have received strong CYP3A4 enzyme-inducing anticonvulsants within 14 days prior to enrollment
• Patients must not have received prior exposure to exatecan or deruxtecan based ADCs. Patients with documented progression while on active treatment with a TOP1 inhibitor containing regimen will be excluded
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
• Patients with known current active CNS primary disease or CNS metastasis whether symptomatic or discovered incidentally without clinical symptoms, are not eligible

Sponsors & Collaborators

• Children's Oncology Group: lead

MeSH Terms

Conditions

Sarcoma, Ewing; Rhabdomyosarcoma

Interventions

Specimen Handling

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Myosarcoma; Neoplasms, Muscle Tissue

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Juan C Vasquez

  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 15, 2026
• First Posted: September 21, 2026
• Study Start (Estimated): May 7, 2027
• Primary Completion (Estimated): June 30, 2033
• Study Completion (Estimated): June 30, 2033
• Last Updated: September 22, 2026

Record last verified: 2026-09