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Recurrent Childhood Ewing SarcomaPhase 1/2NCT07830667

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

A Phase 1/2 study testing Archive Sample Retrieval, Biospecimen Collection and pH Low Insertion Peptide-exatecan Conjugate CBX-12 in people with Recurrent Childhood Ewing Sarcoma and Recurrent Childhood Malignant Solid Neoplasm, run by Children's Oncology Group.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record

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Trial 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… Read more about this study

Who is it for?
Ages 12 months to 30 years
What is being tested?
Archive Sample Retrieval, Biospecimen Collection and pH Low Insertion Peptide-exatecan Conjugate CBX-12
Could I receive a placebo?
No, everyone receives an active treatment
How many people
79 participants
Where
No sites listed yet
Study dates
7 May 2027to 30 Jun 2033
Phase
Phase 1/2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 months to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
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  • 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
  • Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
  • Interleukins, interferons and cytokines (other than hematopoietic growth factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
  • Stem cell infusions (with or without total body irradiation [TBI]):
  • Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: ≥ 84 days after infusion and no evidence of graft versus host disease (GVHD)
  • Autologous stem cell infusion including boost infusion: ≥ 42 days
  • Cellular therapy: ≥ 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.)
  • X-ray therapy (XRT)/external beam irradiation including protons: ≥ 14 days after local XRT; ≥ 150 days after TBI, craniospinal XRT or if radiation to ≥ 50% of the pelvis; ≥ 42 days if other substantial bone marrow (BM) radiation
  • Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 [131I MIBG]): ≥ 42 days after systemically administered radiopharmaceutical therapy
  • For patients with solid tumors without known bone marrow involvement: peripheral absolute neutrophil count (ANC) ≥ 1,000/µL
  • For patients with solid tumors without known bone marrow involvement: platelet count ≥ 100,000/µL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
  • For patients with solid tumors without known bone marrow involvement: hemoglobin ≥ 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions)
  • Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
  • A creatinine based on age/sex as follows:
  • Age: 1 to < 2 years; maximum serum creatinine (mg/dL): 0.6 (male), 0.6 (female)
  • Age: 2 to < 6 years; maximum serum creatinine (mg/dL): 0.8 (male), 0.8 (female)
  • Age: 6 to < 10 years; maximum serum creatinine (mg/dL): 1 (male), 1 (female)
  • Age: 10 to < 13 years; maximum serum creatinine (mg/dL): 1.2 (male), 1.2 (female)
  • Age: 13 to < 16 years; maximum serum creatinine (mg/dL): 1.5 (male), 1.4 (female)
  • Age: ≥ 16 years; maximum serum creatinine (mg/dL): 1.7 (male), 1.4 (female)
  • A 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m^2 OR a glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
  • Note: estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
  • Bilirubin (total or sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age, except in patients diagnosed with Gilbert's disease, for whom bilirubin must be ≤ 3.0 × ULN
  • Alanine aminotransferase (ALT) ≤ 3 x ULN
  • Aspartate aminotransferase (AST) ≤ 3 x ULN
  • Albumin ≥ 2 g/dL
  • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days. If needed, evaluate use of enzyme-inducing anticonvulsants
  • Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v]5) resulting from prior therapy must be ≤ grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
  • Pulse oximetry > 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest)
  • Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

Who cannot join

  • 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
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  • 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

About this study

Official title: A Phase 1/2 Study of CBX-12 in Pediatric Patients With Relapsed or Refractory Solid Tumors

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of pH low insertion peptide-exatecan conjugate CBX-12 (CBX-12) administered as an intravenous (IV) infusion once weekly in 21-day cycles to children with recurrent or refractory extracranial solid tumors. (Part A Phase 1 Dose Escalation) II. To define and describe the toxicities of CBX-12 administered on this schedule. (Part A Phase 1 Dose Escalation) III. To characterize the pharmacokinetics of CBX-12 in children and adolescents with recurrent or refractory extracranial solid tumors. (Part A Phase 1 Dose Escalation) IV. To estimate the preliminary antitumor activity of CBX-12 in a disease-specific expansion cohort of patients with recurrent or refractory rhabdomyosarcoma. (Part B Phase 2 Dose Expansion) V. To estimate the preliminary antitumor activity of CBX-12 in a disease-specific expansion cohort of patients with recurrent or refractory Ewing sarcoma. (Part B Phase 2 Dose Expansion)

SECONDARY OBJECTIVE:

  1. To preliminarily determine the antitumor activity of CBX-12 across patients with recurrent or refractory solid tumors within the confines of a phase 1 study. (Part A Phase 1 Dose Escalation)

EXPLORATORY OBJECTIVES:

  1. To assess whether the activity of CBX-12 is influenced by tumor expression of SLFN11 and/or CAIX.

II. To assess whether the activity of CBX-12 is associated with an homologous recombination deficient (HRD) or deoxyribonucleic acid (DNA) repair deficient profile of tumors, as measured by whole exome sequencing.

III. To assess whether the activity of CBX-12 is influenced by the metabolic profile of tumors as measured by liquid chromatography (LC)-mass spectrometry (MS)/MS.

IV. To assess the biologic activity of CBX-12 by immunohistochemical assessments of pH2AX in paired optional tumor biopsies before and after treatment.

OUTLINE: This is a phase I, dose-escalation study of CBX-12 followed by a phase II dose-expansion study.

Patients receive CBX-12 intravenously (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.

After completion of study treatment, patients are followed up in months 3, 6, 9, 12, 18, 24, 36, 48, and 60.

Being tested
Archive Sample Retrieval, Biospecimen Collection, pH Low Insertion Peptide-exatecan Conjugate CBX-12, Radiologic Imaging Procedure
Medical subject headings
Sarcoma, Ewing, Rhabdomyosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Archive Sample RetrievalProcedure or surgery

    Also called ARCHIVE RETRIEVING

    Ancillary studies

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of bone marrow and blood samples

  • pH Low Insertion Peptide-exatecan Conjugate CBX-12Drug

    Also called Alphalex Conjugate CBX-12, Alphalex-exatecan Conjugate CBX-12, CBX 12, CBX-12

    Given IV

  • Radiologic Imaging ProcedureProcedure or surgery

    Undergo radiologic imaging

Study groups in NCT07830667
Study groupRoleWhat they receive
Treatment (CBX-12)ExperimentalPatients 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.
Receives: Procedure: Archive Sample Retrieval; Procedure: Biospecimen Collection; Drug: pH Low Insertion Peptide-exatecan Conjugate CBX-12; Procedure: Radiologic Imaging Procedure

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

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

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

  3. 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.

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

  4. 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).

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

  5. 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.

    Measured: Up to 60 months

Secondary outcomes (1)

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

    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 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.

    Measured: During part A phase 1 dose escalation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2026
  2. Study start7 May 2027 (estimated)
  3. Primary completion30 Jun 2033 (estimated)
  4. Study completion30 Jun 2033 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
79 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07830667
Sponsor's protocol ID
PEPN2612
Other IDs
NCI-2026-06652, PEPN2612, PEPN2612, UM1CA228823
Status last verified
Sep 2026
First submitted
15 Sep 2026
Last updated
22 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

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