A Study of CBX-250 in Participants With Relapsed or Refractory Myeloid Leukemias

NCT06994676 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CBX-250-001
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 11

Brief Summary

Study CBX-250-001 is a Phase 1, open-label, dose-escalation study of CBX-250 in participants with relapsed/refractory AML, HR-MDS, CMML, and CML. 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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (5)

• To determine the safety, tolerability, RP2D, or MTD if different, and dosing regimen of CBX-250.

  Frequency and type of DLT

  Until the end of study (approximately 24 months)

• To determine the safety, tolerability, RP2D, or MTD if different, and dosing regimen of CBX-250.

  Frequency, duration, and severity of TEAEs, TRAEs, AESIs, and SAEs

  Until the end of study (approximately 24 months)

• To determine the safety, tolerability, RP2D, or MTD if different, and dosing regimen of CBX-250.

  Frequency and severity of CRS AEs

  Until the end of study (approximately 24 months)

• To determine the safety, tolerability, RP2D, or MTD if different, and dosing regimen of CBX-250.

  Drug withdrawals, drug interruptions, or dose reductions due to adverse events

  Until the end of study (approximately 24 months)

• To determine the safety, tolerability, RP2D, or MTD if different, and dosing regimen of CBX-250.

  Incidence/shifts of clinical laboratory abnormalities

  Until the end of study (approximately 24 months)

Secondary Outcomes (16)

• AUC0-t (first dose and at steady state)

  Approximately 1 year

• Cmax

  Approximately 1 year

• Tmax

  Approximately 1 year

• ADAs

  Approximately 1 year

• ORR

  Approximately 1 year

Study Arms (1)

CBX-250

EXPERIMENTAL

subcutaneous CBX-250

Drug: CBX-250

Interventions

CBX-250 DRUG

subcutaneous CBX-250

CBX-250

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:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Age
• Dose Escalation: Male or female participants aged ≥18 years.
• Backfill Cohorts: Male or female participants aged ≥12 years for whom no curative treatment options, including transplantation, are available.
• Diagnosis \& Disease Characteristics
• Participants with histological confirmation of advanced hematologic malignancy including:
• 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.
• 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).
• R/R CMML who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine).
• White blood cells must be below 25,000/µL at time of enrollment. Participants may receive cytoreduction prior to enrollment.
• Historical documented evidence of HLA-A\*02:01 allele positivity.
• Performance Level
• 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).
• Prior Therapy
• Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with the exception of ≤Grade 2 alopecia.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Diagnosis
• Previous CTSG targeted therapy or treatment with any pMHC T-cell engager.
• Isolated extramedullary relapse.
• 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).
• Infection
• Known HIV infection.
• Active hepatitis B infection (participants with documented clearance following treatment are allowed).
• Active hepatitis C infection (participants with documented clearance following treatment are allowed).
• Pregnancy and Breastfeeding
• 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.
• Concurrent Conditions
• 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

Sponsors & Collaborators

• Crossbow Therapeutics, Inc.: lead

Study Sites (11)

City of Hope

Duarte, California, 91010, United States

RECRUITING

Stanford Medical Center

Palo Alto, California, 94304, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Northwestern Medicine

Chicago, Illinois, 60611, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Washington University in St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Sarah Cannon Cancer Institute

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myeloproliferative Disorders

Study Officials

• Briggs Morrison, MD

  Crossbow Therapeutics, Inc.

  STUDY CHAIR

Central Study Contacts

Rachel Ghiraldi

CONTACT

857-301-6432; rachel.ghiraldi@crossbowtx.com

Study Design

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

Study Record Dates

• First Submitted: May 13, 2025
• First Posted: May 29, 2025
• Study Start: July 16, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: One year after publication
• Access Criteria: Requests to be reviewed on an individual basis by Crossbow Therapeutics, Inc.

Locations

US (11)