Testing How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers

NCT05691517 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: NCI-2022-1103400103110577
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Metastatic Malignant Solid Neoplasm; Advanced Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Early Rad51/deoxyribonucleic acid (DNA) damage response (DDR)

  At cycle 1 day 2 (1 cycle = 28 days)

• Late Rad51/DDR response

  At cycle 3 day 1

Secondary Outcomes (3)

• Tumor TOP1 molecular response

  Up to 24-30 hours post-first dose

• DDR modulation and plasma exatecan concentrations

  Up to 2 years

• CD8 T cell infiltration and activation in tumor

  Up to 2 years

Other Outcomes (5)

• Molecular markers of apoptosis

  Up to 2 years

• Genomic or gene expression characteristics in tumor that may be associated with sensitivity or resistance to CBX-12

  Up to 2 years

• Genomic alterations in circulating tumor DNA that may be associated with sensitivity or resistance to CBX-12

  Up to 2 years

Study Arms (1)

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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: pH Low Insertion Peptide-exatecan Conjugate CBX-12

Interventions

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (CBX-12)

pH Low Insertion Peptide-exatecan Conjugate CBX-12 DRUG

Given IV

Also known as: Alphalex Conjugate CBX-12, Alphalex-exatecan Conjugate CBX-12, CBX 12, CBX-12, CBX12, Low pH Targeting Alphalex-exatecan Conjugate CBX-12, pHLIP-exatecan Conjugate CBX-12

Treatment (CBX-12)

Biopsy Procedure PROCEDURE

Undergo tumor biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (CBX-12)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (CBX-12)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, 20892, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Biopsy; Specimen Handling

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Alice P Chen

  National Cancer Institute LAO

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 18, 2023
• First Posted: January 20, 2023
• Study Start: June 12, 2024
• Primary Completion (Estimated): October 15, 2026
• Study Completion (Estimated): October 15, 2026
• Last Updated: May 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)