Trial Title:
Testing How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers
NCT ID:
NCT05691517
Condition:
Advanced Malignant Solid Neoplasm
Metastatic Malignant Solid Neoplasm
Conditions: Official terms:
Neoplasms
Exatecan
Camptothecin
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo tumor biopsy
Arm group label:
Treatment (CBX-12)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (CBX-12)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Treatment (CBX-12)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
pH Low Insertion Peptide-exatecan Conjugate CBX-12
Description:
Given IV
Arm group label:
Treatment (CBX-12)
Other name:
Alphalex Conjugate CBX-12
Other name:
Alphalex-exatecan Conjugate CBX-12
Other name:
CBX 12
Other name:
CBX-12
Other name:
CBX12
Other name:
Low pH Targeting Alphalex-exatecan Conjugate CBX-12
Other name:
pHLIP-exatecan Conjugate CBX-12
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.
Detailed description:
PRIMARY OBJECTIVE:
I. 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:
I. 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.
V. Assess safety and tolerability of CBX-12.
EXPLORATORY OBJECTIVES:
I. 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).
V. 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
National Cancer Institute Developmental Therapeutics Clinic
Address:
City:
Bethesda
Zip:
20892
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-411-1222
Investigator:
Last name:
A P. Chen
Email:
Principal Investigator
Start date:
June 12, 2024
Completion date:
October 15, 2026
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05691517
