Study Stopped
no accruals
CBX-12 for the Treatment of Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer
Phase 2 Trial of CBX-12 for Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer
3 other identifiers
interventional
N/A
1 country
15
Brief Summary
This phase II trial studies how well CBX-12 works in treating patients with microsatellite stable colorectal cancer that has spread to other parts of the body (metastatic) and is no longer responding to chemotherapy treatment (chemotherapy-refractory). The usual approach to treating colorectal cancer includes treatment with surgery, radiation, or Food and Drug Administration (FDA)-approved drugs such as trifluridine-tipiracil, bevacizumab, regorafenib, or fruquintinib. However, most metastatic colorectal patients progress through all approved treatments and eventually succumb to their disease. CBX-12 is a drug that contains a peptide (a substance that contains many amino acids \[molecules that join together to form proteins\]) called pHLIP, linked to an anticancer substance called exatecan. Upon administration, pHLIP gets inserted into the cellular membrane of tumor cells, delivering exatecan to kill them. Giving CBX-12 may work better than the usual approach in treating patients with metastatic chemotherapy-refractory microsatellite stable colorectal cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Feb 2026
Shorter than P25 for phase_2
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 11, 2024
CompletedFirst Posted
Study publicly available on registry
December 12, 2024
CompletedStudy Start
First participant enrolled
February 17, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2026
October 6, 2025
October 1, 2025
10 months
December 11, 2024
October 3, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Objective response rate (ORR)
Treatment response will be assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Objective response will be defined as either complete response or partial response. Simon's 2-stage optimal design will be used.
From registration to disease progression or death due to any cause, assessed up to 12 months
Dose limiting toxicities (DLTs)
DLTs will be defined as any grade \>= 3 non-hematologic toxicity irrespective of adequate supportive treatment, or grade \>= 4 hematologic toxicity per Common Terminology Criteria for Adverse Events version 5.0 attributed as possibly, probably, or definitely related to drug. The ORR will be estimated along with the 95% confidence interval.
Baseline up to 12 months
Secondary Outcomes (3)
Pharmacodynamics of CBX-12 by DDR3 and apoptosis
Baseline to 12 months
Progression-free survival (PFS)
From registration to disease progression or death due to any cause, assessed up to 12 months
Overall survival (OS)
From registration to disease progression or death due to any cause, assessed up to 12 months
Other Outcomes (7)
Tissue and plasma pharmacokinetics (PK) of CBX-12 and free exatecan
From baseline to 12 months
Variant allele frequencies (VAF) of tumor mutations in circulating tumor DNA (ctDNA)
Baseline and at cycle 3
Incidence and grades of adverse events
Baseline up to 12 months
- +4 more other outcomes
Study Arms (1)
Treatment (CBX-12)
EXPERIMENTALPatients receive CXB-12 IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo x-rays during screening, and CT, MRI, and blood collection throughout the study and patients may undergo biopsy during screening and on study.
Interventions
Undergo blood sample collection
Undergo CT scan
Undergo MRI
Given IV
Undergo chest x-rays
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed metastatic colorectal cancer (mCRC) that is mismatch repair proficient (pMMR) based on local testing performed in a Clinical Laboratory Improvement Act (CLIA) lab
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) by chest x-ray or as \>= 10 mm (\>= 1 cm) with CT scan, MRI, or calipers by clinical exam
- Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment, with no Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 toxicity of grade 3 or higher at the time of enrollment
- Availability of archival tumor tissue at the time of patient enrollment for molecular profiling studies
- Patients must have progressed on or been intolerant to at least 2 lines of prior therapies:
- Have progressed on or intolerant of standard therapies, including a fluoropyrimidine (5-fluorouracil or capecitabine), oxaliplatin, irinotecan, and VEGF inhibitor (bevacizumab or biosimilar).
- If left-sided primary and RAS/RAF wild-type, then have progressed on or intolerant of EGFR inhibitor (cetuximab or panitumumab).
- If BRAF V600 mutation, then have progressed on or intolerant of BRAF inhibitor (encorafenib).
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of CBX-12 in patients \<18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
- Absolute neutrophil count \>= 1,000/mcL
- Platelets \>= 100,000/mcL
- Hemoglobin \>= 8.0 g/dL
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 Ă— institutional ULN
- +11 more criteria
You may not qualify if:
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
- Patients who are receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to CBX-12
- Patients with concurrent administration of medication expected to cause drug interactions with CBX-12, including strong inducers and strong inhibitors of CYP3A4/1A2 isoenzymes or sensitive substrates of CYP3A4/2B6, OATP1B1, OATP1B3, OAT1, and MATE-2k
- Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
- Pregnant women are excluded from this study because CBX-12 is a topoisomerase 1 inhibitors agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CBX-12, breastfeeding should be discontinued if the mother during treatment with CBX-12 and for at least 4 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610, United States
Northwestern University
Chicago, Illinois, 60611, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Chaoyuan Kuang
UPMC Hillman Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 11, 2024
First Posted
December 12, 2024
Study Start
February 17, 2026
Primary Completion (Estimated)
December 1, 2026
Study Completion (Estimated)
December 1, 2026
Last Updated
October 6, 2025
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.