Advanced Malignant Solid NeoplasmPhase 1NCT05691517
Testing How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers
A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Advanced Malignant Solid Neoplasm and Metastatic Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial studies how well CBX-12 works in treating patients with solid tumors that have spread from where they first started (primary site) to started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or other places in the body (metastatic). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jun 2024to 15 Oct 2028
- Phase
- Phase 1
- 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 confirmed solid tumors with metastatic disease that have progressed after >= 1 line of prior therapy
- Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, with 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)
- Patients must have a tumor site amenable to biopsy
- Age >= 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Absolute neutrophil count >= 1,500/mcL
Show all 30Show fewer
- Hemoglobin >= 9 g/L
- Platelets >= 100,000/mcL
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
- However, patients with known Gilbert disease who have serum bilirubin level of up to 3 mg/dl may be enrolled
- International normalized ratio (INR) or activated partial thromboplastin time (aPTT) =< 1.5 institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) =< 3 x institutional ULN
- AST and/or ALT =< 5 x ULN for patients with liver involvement
- Potassium ≥ lower limit of normal (LLN)
- Subjects may receive supplementation to meet this eligibility criteria
- Magnesium ≥ LLN
- Subjects may receive supplementation to meet this eligibility criteria
- Ionized/corrected calcium ≥ LLN
- Subjects may receive supplementation to meet this eligibility criteria
- Creatinine =< 1.5 x institutional ULN or creatinine clearance levels >= 60 ml/min based on the Cockcroft-Gault formula
- Oxygen (O2) saturation > 90% on room air
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. For these patients, an HIV viral load test must be completed within 28 days prior to enrollment
- 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 >= 1 month after treatment of the brain metastases
- 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 2B or better
- The effects of CBX-12 on the developing human fetus are unknown. For this reason and because biologicals conjugated to topoisomerase 1 inhibitor agents 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 or abstinence) prior to study entry and for the duration of study participation and for at least 4 months after the last dose of study drug. 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. Women should not breastfeed while taking CBX-12 and for 4 months after cessation of treatment. 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
- Willingness to provide biopsy samples for research purposes
- 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 must have recovered from clinically-significant adverse-events of their most recent cancer immunotherapy to grade 1 or less (with the exception for alopecia or lymphopenia)
- Eligibility of subjects receiving any medications or substances with the potential to affect the activity of CBX-12 or exatecan will be determined following review of their cases by the Principal Investigator
- Patients who are receiving any other investigational agents
- Patients taking medication known to prolong the QT interval, or receiving any medications or substances that are strong CYP3A4 or CYP1A2 inhibitors or inducers, and sensitive substrates of CYP3A or CYP2B6 with a narrow therapeutic index are ineligible, if they cannot be transferred to alternative medication. Patients on substrates of OATP1B1 and OATP1B3 should be excluded unless they can be transferred on alternative medication. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. 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
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to CBX-12 (e.g., other topoisomerase I inhibitors) or the inactive ingredients in the drug product
- Patients with uncontrolled intercurrent illness that would limit compliance with study requirements
- Pregnant women are excluded from this study because CBX-12 is an investigational agent with unknown potential for teratogenic or abortifacient effects. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) for the duration of study participation and for at least 4 months after the last dose of the study. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother and because it is not known if the agent can be excreted in human milk, breastfeeding should be discontinued while the mother is taking CBX-12 and for 4 months after cessation of treatment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, 20892
Site Public Contact, 800-411-1222
A P. Chen
About this study
Official title: Pilot Study of CBX-12 Pharmacodynamics in Patients With Advanced Solid Tumors
This phase I trial studies how well CBX-12 works in treating patients with solid tumors that have spread from where they first started (primary site) to started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or other places in the body (metastatic). CBX-12 works by binding to a protein called TOP1 that is present inside the cells. This allows CBX-12 to kill the cancer cells by damaging their DNA, resulting in cancer cell death. This trial is being done to find out if this approach is better or worse than the usual approach for advanced cancers.
Read the detailed description
PRIMARY OBJECTIVE:
- Assess the effects of CBX-12 on biomarkers of DDR in biopsy specimens from patients with advanced solid tumors at baseline and 24-30 hours post-first dose to establish the degree and duration of CBX-12 target engagement.
SECONDARY OBJECTIVES:
- Assess the effects of CBX-12 on tumor TOP1 molecular response at baseline and 24-30 hours post-first dose.
II. Determine any association between tumor TOP1 and DDR modulation and plasma exatecan concentrations.
III. Evaluate the effects of CBX-12 on CD8 T cell infiltration and activation in tumor.
IV. Determine the objective response rate (ORR) of patients with advanced cancers to CBX-12 using RECIST v 1.1.
- Assess safety and tolerability of CBX-12.
EXPLORATORY OBJECTIVES:
- Measure the effects of CBX-12 on molecular markers of apoptosis. II. Examine any genomic or gene expression characteristics in tumor that may be associated with sensitivity or resistance to CBX-12.
III. Examine any genomic alterations in circulating free deoxyribonucleic acid (DNA) (cfDNA) that may be associated with sensitivity or resistance to CBX-12.
IV. Measure changes in levels of any anti-drug antibodies that may develop during CBX-12 therapy (Cybrexa assay).
- Examine the molecular context of drug sensitivity or resistance (e.g., SLFN11 expression).
OUTLINE:
Patients receive CBX-12 intravenously (IV), over 60 minutes, on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy and computed tomography (CT) scans on study and undergo blood sample collection throughout the trial.
After completion of study treatment, patients follow up at 30 days.
- Being tested
- Biopsy Procedure, Biospecimen Collection, Computed Tomography, pH Low Insertion Peptide-exatecan Conjugate CBX-12
- Medical subject headings
- Neoplasm Metastasis
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 tumor 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
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
| Study group | Role | What they receive |
|---|---|---|
| Treatment (CBX-12) | Experimental | Aatients receive CBX-12 IV, over 60 minutes, on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy and CT scans on study and undergo blood sample collection throughout the trial. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: pH Low Insertion Peptide-exatecan Conjugate CBX-12 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early Rad51/deoxyribonucleic acid (DNA) damage response (DDR)
Measured: At cycle 1 day 2 (1 cycle = 28 days)
Late Rad51/DDR response
Measured: At cycle 3 day 1
Secondary outcomes (3)
Tumor TOP1 molecular response
Measured: Up to 24-30 hours post-first dose
DDR modulation and plasma exatecan concentrations
Association between tumor TOP1 and DDR modulation and plasma exatecan concentrations will be determined.
Measured: Up to 2 years
CD8 T cell infiltration and activation in tumor
The effects of CBX-12 on CD8 T cell infiltration and activation in tumor will be evaluated.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2023
- Study start12 Jun 2024
- Primary completion15 Oct 2028 (estimated)
- Study completion15 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Malignant Solid NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Alice P Chen, Principal investigator, National Cancer Institute LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05691517
- Sponsor's protocol ID
- NCI-2022-11034
- Other IDs
- NCI-2022-11034, 001031, 10577, 10577
- Status last verified
- Oct 2026
- First submitted
- 18 Jan 2023
- Last updated
- 15 Oct 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.
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of CBX-12 Pharmacodynamics in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT05691517
- Acronym / sponsor ID
- NCI-2022-11034
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 12 Jun 2024 (actual)
- Primary completion
- 15 Oct 2028 (estimated)
- Study completion
- 15 Oct 2028 (estimated)
- First posted
- 20 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies how well CBX-12 works in treating patients with solid tumors that have spread from where they first started (primary site) to started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or other places in the body (metastatic). CBX-12 works by binding to a protein called TOP1 that is present inside the cells. This allows CBX-12 to kill the cancer cells by damaging their DNA, resulting in cancer cell death. This trial is being done to find out if this approach is better or worse than the usual approach for advanced cancers.
Detailed description
PRIMARY OBJECTIVE:
- Assess the effects of CBX-12 on biomarkers of DDR in biopsy specimens from patients with advanced solid tumors at baseline and 24-30 hours post-first dose to establish the degree and duration of CBX-12 target engagement.
SECONDARY OBJECTIVES:
- Assess the effects of CBX-12 on tumor TOP1 molecular response at baseline and 24-30 hours post-first dose.
II. Determine any association between tumor TOP1 and DDR modulation and plasma exatecan concentrations.
III. Evaluate the effects of CBX-12 on CD8 T cell infiltration and activation in tumor.
IV. Determine the objective response rate (ORR) of patients with advanced cancers to CBX-12 using RECIST v 1.1.
- Assess safety and tolerability of CBX-12.
EXPLORATORY OBJECTIVES:
- Measure the effects of CBX-12 on molecular markers of apoptosis. II. Examine any genomic or gene expression characteristics in tumor that may be associated with sensitivity or resistance to CBX-12.
III. Examine any genomic alterations in circulating free deoxyribonucleic acid (DNA) (cfDNA) that may be associated with sensitivity or resistance to CBX-12.
IV. Measure changes in levels of any anti-drug antibodies that may develop during CBX-12 therapy (Cybrexa assay).
- Examine the molecular context of drug sensitivity or resistance (e.g., SLFN11 expression).
OUTLINE:
Patients receive CBX-12 intravenously (IV), over 60 minutes, on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy and computed tomography (CT) scans on study and undergo blood sample collection throughout the trial.
After completion of study treatment, patients follow up at 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (CBX-12) | Experimental | Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Procedure: Computed Tomography, Drug: pH Low Insertion Peptide-exatecan Conjugate CBX-12Aatients receive CBX-12 IV, over 60 minutes, on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy and CT scans on study and undergo blood sample collection throughout the trial. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Patients must have histologically confirmed solid tumors with metastatic disease that have progressed after >= 1 line of prior therapy
- Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, with 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)
- Patients must have a tumor site amenable to biopsy
- Age >= 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
Key exclusion criteria (7 listed)
- Patients must have recovered from clinically-significant adverse-events of their most recent cancer immunotherapy to grade 1 or less (with the exception for alopecia or lymphopenia)
- Eligibility of subjects receiving any medications or substances with the potential to affect the activity of CBX-12 or exatecan will be determined following review of their cases by the Principal Investigator
- Patients who are receiving any other investigational agents
- Patients taking medication known to prolong the QT interval, or receiving any medications or substances that are strong CYP3A4 or CYP1A2 inhibitors or inducers, and sensitive substrates of CYP3A or CYP2B6 with a narrow therapeutic index are ineligible, if they cannot be transferred to alternative medication. Patients on substrates of OATP1B1 and OATP1B3 should be excluded unless they can be transferred on alternative medication. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. 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
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to CBX-12 (e.g., other topoisomerase I inhibitors) or the inactive ingredients in the drug product
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biopsy ProcedureAlso: Biopsy, BIOPSY_TYPE, BxUndergo tumor biopsy | Procedure or surgery | Treatment (CBX-12) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen CollectionUndergo blood sample collection | Procedure or surgery | Treatment (CBX-12) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT scan | Procedure or surgery | Treatment (CBX-12) |
| pH Low Insertion Peptide-exatecan Conjugate CBX-12Also: Alphalex Conjugate CBX-12, Alphalex-exatecan Conjugate CBX-12, CBX 12, CBX-12Given IV | Drug | Treatment (CBX-12) |
Primary outcome
Early Rad51/deoxyribonucleic acid (DNA) damage response (DDR)
Time frame: At cycle 1 day 2 (1 cycle = 28 days)
Late Rad51/DDR response
Time frame: At cycle 3 day 1
3 secondary outcomes
Tumor TOP1 molecular response
Time frame: Up to 24-30 hours post-first dose
DDR modulation and plasma exatecan concentrations
Time frame: Up to 2 years
CD8 T cell infiltration and activation in tumor
Time frame: Up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Alice P Chen principal investigator
National Cancer Institute LAO
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Advanced Malignant Solid Neoplasm and Metastatic Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 1 site 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 30 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Early Rad51/deoxyribonucleic acid (DNA) damage response (DDR) (time frame: At cycle 1 day 2 (1 cycle = 28 days)). 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?
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 15 Oct 2026.