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Metastatic Mismatch Repair Proficient Colorectal CarcinomaPhase 2NCT06730100

CBX-12 for the Treatment of Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer

A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Metastatic Mismatch Repair Proficient Colorectal Carcinoma and Refractory Mismatch Repair Proficient Colorectal Carcinoma, run by National Cancer Institute (NCI) at 15 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy Procedure, Biospecimen Collection and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
15 sitesUnited States
Study dates
11 Sep 2025to 1 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
Show all 26Show fewer
  • 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 × institutional ULN
  • Glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for at least 4 weeks
  • Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
  • Patients are willing and able to undergo pre- and on-treatment biopsies (first 10 patients in stage 1 only)
  • The effects of CBX-12 on the developing human fetus are unknown. For this reason and because topoisomerase 1 inhibitors are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 6 months after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of CBX-12 administration
  • Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

Who cannot join

  • 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

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

    Irvine, California, 92612

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

    Madison, Wisconsin, 53718

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • University of Cincinnati Cancer Center-West Chester

    West Chester, Ohio, 45069

Other trials in United States

About this study

Official title: Phase 2 Trial of CBX-12 for Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the clinical activity, as determined by response rate, of pH low insertion peptide-exatecan conjugate CBX-12 (CBX-12) in microsatellite stable/mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (mCRC) patients.

SECONDARY OBJECTIVES:

  1. To evaluate the pharmacodynamics of CBX-12 (DDR3 and apoptosis). II. To determine the effect of CBX-12 on progression-free survival (PFS).

EXPLORATORY OBJECTIVES:

  1. To evaluate the tissue and plasma pharmacokinetics (PK) of CBX-12 and free exatecan.

II. To evaluate circulating tumor deoxyribonucleic acid (DNA) (ctDNA) as a predictor for treatment response to CBX-12.

III. To evaluate the safety and tolerability of CBX-12 dosed every 21 days. IV. To evaluate biomarkers of response to CBX-12 (DNA damage response, apoptosis, SLFN11 expression, TOP1-DNA complex).

OUTLINE:

Patients receive CXB-12 intravenously (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 computed tomography (CT), magnetic resonance imaging (MRI), and blood collection throughout the study and patients may undergo biopsy during screening and on study.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for 12 months or until death.

Being tested
Biopsy Procedure, Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging, pH Low Insertion Peptide-exatecan Conjugate CBX-12
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

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

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • 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

  • X-Ray ImagingProcedure or surgery

    Also called Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs

    Undergo chest x-rays

Study groups in NCT06730100
Study groupRoleWhat they receive
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.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: pH Low Insertion Peptide-exatecan Conjugate CBX-12; Procedure: X-Ray Imaging

What is being measured

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

  1. 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.

    Measured: From registration to disease progression or death due to any cause, assessed up to 12 months

  2. 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.

    Measured: Baseline up to 12 months

Secondary outcomes (3)

  1. Pharmacodynamics of CBX-12 by DDR3 and apoptosis

    Percent of tumor cells positive for deoxyribonucleic acid (DNA) damage marker γH2AX and percent of tumor cells positive for apoptosis marker cleaved caspase 3. Pre- and on-treatment comparisons will be made within patients who provide evaluable paired biopsies, using a paired t-test. A nonparametric method will be pursued as needed. Assuming an 80% evaluable biopsy rate out of 17 patients, we would obtain 14 evaluable pre-treatment and 14 evaluable post-treatment biopsies. Using a one-sided paired t-test at a type I error rate of 0.05, this study achieves 80% power to detect a mean paired difference of 0.6 standard deviation of differences, which is deemed to be a medium effect size (Cohen, 1992). In addition, will fit a logistic regression on objective response with increase in %γH2AX-positive tumor cells and increase in %caspase 3-positive tumor cells, separately as well as simultaneously.

    Measured: Baseline to 12 months

  2. Progression-free survival (PFS)

    PFS and OS will be estimated by the Kaplan-Meier method, along with 95% confidence regions. The median time will be estimated and compared with 5.6 months of PFS and 10.8 months (Prager et al., 2023). One-sample log-rank tests will be performed against the reference curves from Prager et al. (Prager et al., 2023).

    Measured: From registration to disease progression or death due to any cause, assessed up to 12 months

  3. Overall survival (OS)

    PFS and OS will be estimated by the Kaplan-Meier method, along with 95% confidence regions. The median time will be estimated and compared with 5.6 months of PFS and 10.8 months (Prager et al., 2023). One-sample log-rank tests will be performed against the reference curves from Prager et al. (Prager et al., 2023).

    Measured: From registration to disease progression or death due to any cause, assessed up to 12 months

Timeline

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

  1. First posted12 Dec 2024
  2. Study start11 Sep 2025
  3. Primary completion1 Dec 2026 (estimated)
  4. Study completion1 Dec 2026 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06730100
Sponsor's protocol ID
NCI-2024-10048
Other IDs
NCI-2024-10048, 10707, 10707, UM1CA186690
Status last verified
Oct 2026
First submitted
11 Dec 2024
Last updated
3 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Metastatic Mismatch Repair Proficient Colorectal Carcinoma and Refractory Mismatch Repair Proficient Colorectal Carcinoma, run by National Cancer Institute (NCI) at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) (time frame: From registration to disease progression or death due to any cause, assessed up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06730100.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.

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