RECRUITING

A Study of CBX-250 in Participants With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

Conditions

High-risk Myelodysplastic Syndrome Chronic Myelomonocytic Leukemia (CMML)AML - Acute Myeloid Leukemia AML HR-MDS CMML acute leukemia CBX-250 CBX-250-001 CROSSCHECK CROSSCHECK-001 Crossbow

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Study CBX-250-001 is a Phase 1, open-label, dose-escalation study of CBX-250 in participants with relapsed/refractory AML, HR-MDS and CMML. Participants aged ≥ 12 years are planned to be enrolled. CBX-250 will initially be investigated on a fixed step-up dosing schedule. CBX-250 will be administered subcutaneously in 28-day cycles, with the first study drug dose administered on Cycle 1, Day 1. Cycle 1 will consist of a priming phase over 7 days, and a target phase over 28 days. Participants will continue CBX-250 until progressive disease (PD) or unacceptable toxicity. All subsequent treatment cycles will be 28 days.

Official Title

CROSSCHECK-001: A Phase 1, Open-Label, Dose-Escalation Study to Evaluate Safety, Tolerability, and Clinical Activity of CBX-250 in Participants With Relapsed or Refractory Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

Quick Facts

Study Start:2025-07

Study Completion:2027-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06994676

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Dose Escalation: Male or female participants aged ≥18 years. 2. Backfill Cohorts: Male or female participants aged ≥12 years for whom no curative treatment options, including transplantation, are available. 3. Participants with histological confirmation of advanced hematologic malignancy including: 1. R/R AML, as defined by standardized criteria (e.g., European LeukemiaNet criteria \[Dohner 2022\]; after standard of care therapy. Participants with persistent leukemia after initial therapy or with recurrence of leukemia at any time after achieving a response during or after the course of treatment (including HSCT) are eligible. 2. R/R HR-MDS or very high risk MDS as per the Revised International Prognostic Scoring System (IPSS-R; Greenberg 2012) or Molecular International Prognostic Scoring System (IPPS-M, Bernard 2022) who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine). 3. R/R CMML who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine). 4. White blood cells must be below 25,000/µL at time of enrollment. Participants may receive cytoreduction prior to enrollment. 5. Historical documented evidence of HLA-A\02:01 allele positivity. 6. ECOG PS score 0-1 (if aged ≥18 years); Karnofsky Performance Scale of ≥70 (if aged ≥16 years and \<18 years); Lansky PS of ≥70 (if aged \<16 years). 7. Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with the exception of ≤Grade 2 alopecia. 8. Radiation Therapy: At least 60 days from prior total body irradiation, craniospinal radiation and/or ≥50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port). 9. Stem Cell Infusion: At least 60 days must have elapsed from HSCT and at least 4 weeks (from first dose) must have elapsed from donor lymphocyte infusion without conditioning. 10. Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines and checkpoint inhibitors, and at least 21 days since receipt of chimeric antigen receptor therapy. 11. Anti-Leukemia Therapy: At least 14 days since the completion of anti-leukemic therapy (for example, but not limited to, small molecule or cytotoxic/myelosuppressive therapy), with the following exceptions: Hydroxyurea for cytoreduction can be initiated without restriction related to timing of study entry. Hydroxyurea for cytoreduction can be continued concomitantly with CBX-250, with Study Responsible Physician approval. * Intrathecal chemotherapy at the time of diagnostic lumbar puncture at least 24 hours prior to the start of CBX-250 and may continue prophylactic intrathecal chemotherapy beginning in Cycle 2, at the treating physician's discretion. 12. Hematopoietic Growth Factors: At least 7 days since the completion of therapy with short-acting hematopoietic growth factors and 14 days with long-acting growth factors. 13. Biologics (e.g. monoclonal antibody therapy): At least 28 days or 5 half-lives, whichever is shorter, have elapsed since the completion of therapy with a biologic agent. Any AE related to prior biologic treatment must be resolved to baseline severity or ≤Grade 1. 14. Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing (equivalent to ≤10 mg prednisone daily) or cytoreductive therapy. Cytoreductive therapy must have approval of the Study Responsible Physician. 15. Estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2 based on local institutional practice for age-appropriate determination (eg, Schwartz formula for pediatric participants or Cockcroft-Gault formula for adults). 1. Participants ≥18 years: glomerular filtration rate ≥45 mL/min 2. Participants \<18 years: ≥45 mL/min x (participant's body surface area m2/1.73) • Adequate liver function defined as: * Total bilirubin \<1.5 × the upper limit of normal (ULN) for age or normal conjugated bilirubin, or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in participants with well documented Gilbert's syndrome or hemolysis or who require regular blood transfusions. * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<3 × ULN (unless attributed to leukemic involvement with discussion with the Study Responsible Physician). 16. If a female of childbearing potential, willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose. 17. If male of childbearing potential, agrees to use barrier contraception from the time of enrollment through 120 days following the last study drug dose. 18. Participant or participant's health care proxy is able and willing to provide written informed consent and able to follow study instructions.	1. Previous CTSG targeted therapy or treatment with any pMHC T-cell engager. 2. Isolated extramedullary relapse. 3. Active central nervous system (CNS) disease. Participants with prior CNS history can be enrolled if the participant has a negative lumbar puncture following completion of intrathecal chemotherapy). 4. Known HIV infection. 5. Active hepatitis B infection (participants with documented clearance following treatment are allowed). 6. Active hepatitis C infection (participants with documented clearance following treatment are allowed). 7. Pregnant or nursing women: Negative serum pregnancy tests are required during Screening and a negative serum or urine pregnancy test is required within 72 hours prior to receiving the first study drug administration, in females of childbearing potential. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 8. Cardiac Disease: * Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class \>II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack. * QTc using Fridericia's correction (QTcF) \>480 msec 9. Graft-Versus-Host Disease (GVHD): Active acute or chronic GVHD requiring systemic treatment with immunosuppressive medication. Participants may be on physiological doses of steroids. 10. Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy. Concurrent malignancy must be in CR or no evidence of disease (NED) during this timeframe. 11. History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator's opinion might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate. 12. Any commercially available or investigational anti-leukemic therapy other than CBX-250, with the following exceptions: 13. Participation in another therapeutic interventional clinical study in which an investigational agent was administered within 14 days or 5-halflives, whichever is shorter, of starting CBX-250. Participants may continue with non-interventional follow-up from previous clinical studies. 14. Any concurrent systemic treatment to prevent GVHD. Topical treatments for GVHD are permitted. 15. Known allergy or sensitivity to study drug, including excipients.

Inclusion Criteria

Exclusion Criteria

1. Dose Escalation: Male or female participants aged ≥18 years.
2. Backfill Cohorts: Male or female participants aged ≥12 years for whom no curative treatment options, including transplantation, are available.
3. Participants with histological confirmation of advanced hematologic malignancy including:
1. R/R AML, as defined by standardized criteria (e.g., European LeukemiaNet criteria \[Dohner 2022\]; after standard of care therapy. Participants with persistent leukemia after initial therapy or with recurrence of leukemia at any time after achieving a response during or after the course of treatment (including HSCT) are eligible.
2. R/R HR-MDS or very high risk MDS as per the Revised International Prognostic Scoring System (IPSS-R; Greenberg 2012) or Molecular International Prognostic Scoring System (IPPS-M, Bernard 2022) who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine).
3. R/R CMML who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine).
4. White blood cells must be below 25,000/µL at time of enrollment. Participants may receive cytoreduction prior to enrollment.
5. Historical documented evidence of HLA-A\*02:01 allele positivity.
6. ECOG PS score 0-1 (if aged ≥18 years); Karnofsky Performance Scale of ≥70 (if aged ≥16 years and \<18 years); Lansky PS of ≥70 (if aged \<16 years).
7. Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with the exception of ≤Grade 2 alopecia.
8. Radiation Therapy: At least 60 days from prior total body irradiation, craniospinal radiation and/or ≥50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port).
9. Stem Cell Infusion: At least 60 days must have elapsed from HSCT and at least 4 weeks (from first dose) must have elapsed from donor lymphocyte infusion without conditioning.
10. Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines and checkpoint inhibitors, and at least 21 days since receipt of chimeric antigen receptor therapy.
11. Anti-Leukemia Therapy: At least 14 days since the completion of anti-leukemic therapy (for example, but not limited to, small molecule or cytotoxic/myelosuppressive therapy), with the following exceptions:
* Hydroxyurea for cytoreduction can be initiated without restriction related to timing of study entry. Hydroxyurea for cytoreduction can be continued concomitantly with CBX-250, with Study Responsible Physician approval.
* Intrathecal chemotherapy at the time of diagnostic lumbar puncture at least 24 hours prior to the start of CBX-250 and may continue prophylactic intrathecal chemotherapy beginning in Cycle 2, at the treating physician's discretion.
12. Hematopoietic Growth Factors: At least 7 days since the completion of therapy with short-acting hematopoietic growth factors and 14 days with long-acting growth factors.
13. Biologics (e.g. monoclonal antibody therapy): At least 28 days or 5 half-lives, whichever is shorter, have elapsed since the completion of therapy with a biologic agent. Any AE related to prior biologic treatment must be resolved to baseline severity or ≤Grade 1.
14. Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing (equivalent to ≤10 mg prednisone daily) or cytoreductive therapy. Cytoreductive therapy must have approval of the Study Responsible Physician.
15. Estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2 based on local institutional practice for age-appropriate determination (eg, Schwartz formula for pediatric participants or Cockcroft-Gault formula for adults).
1. Participants ≥18 years: glomerular filtration rate ≥45 mL/min
2. Participants \<18 years: ≥45 mL/min x (participant's body surface area m2/1.73) • Adequate liver function defined as:
* Total bilirubin \<1.5 × the upper limit of normal (ULN) for age or normal conjugated bilirubin, or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in participants with well documented Gilbert's syndrome or hemolysis or who require regular blood transfusions.
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<3 × ULN (unless attributed to leukemic involvement with discussion with the Study Responsible Physician).
16. If a female of childbearing potential, willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose.
17. If male of childbearing potential, agrees to use barrier contraception from the time of enrollment through 120 days following the last study drug dose.
18. Participant or participant's health care proxy is able and willing to provide written informed consent and able to follow study instructions.

1. Previous CTSG targeted therapy or treatment with any pMHC T-cell engager.
2. Isolated extramedullary relapse.
3. Active central nervous system (CNS) disease. Participants with prior CNS history can be enrolled if the participant has a negative lumbar puncture following completion of intrathecal chemotherapy).
4. Known HIV infection.
5. Active hepatitis B infection (participants with documented clearance following treatment are allowed).
6. Active hepatitis C infection (participants with documented clearance following treatment are allowed).
7. Pregnant or nursing women: Negative serum pregnancy tests are required during Screening and a negative serum or urine pregnancy test is required within 72 hours prior to receiving the first study drug administration, in females of childbearing potential. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
8. Cardiac Disease:
* Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class \>II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack.
* QTc using Fridericia's correction (QTcF) \>480 msec
9. Graft-Versus-Host Disease (GVHD): Active acute or chronic GVHD requiring systemic treatment with immunosuppressive medication. Participants may be on physiological doses of steroids.
10. Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy. Concurrent malignancy must be in CR or no evidence of disease (NED) during this timeframe.
11. History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator's opinion might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate.
12. Any commercially available or investigational anti-leukemic therapy other than CBX-250, with the following exceptions:
13. Participation in another therapeutic interventional clinical study in which an investigational agent was administered within 14 days or 5-halflives, whichever is shorter, of starting CBX-250. Participants may continue with non-interventional follow-up from previous clinical studies.
14. Any concurrent systemic treatment to prevent GVHD. Topical treatments for GVHD are permitted.
15. Known allergy or sensitivity to study drug, including excipients.

Contacts and Locations

Study Contact

Rachel Ghiraldi

CONTACT

857-301-6432

rachel.ghiraldi@crossbowtx.com

Principal Investigator

Briggs Morrison, MD

STUDY_CHAIR

Crossbow Therapeutics, Inc.

Study Locations (Sites)

City of Hope

Duarte, California, 91010

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Crossbow Therapeutics, Inc.

Briggs Morrison, MD, STUDY_CHAIR, Crossbow Therapeutics, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-07

Study Completion Date2027-06

Study Record Updates

Study Start Date2025-07

Study Completion Date2027-06

Terms related to this study

Keywords Provided by Researchers

AML
HR-MDS
CMML
acute leukemia
CBX-250
CBX-250-001
CROSSCHECK
CROSSCHECK-001
Crossbow

Additional Relevant MeSH Terms

High-risk Myelodysplastic Syndrome
Chronic Myelomonocytic Leukemia (CMML)
AML - Acute Myeloid Leukemia