Phase Ib Study of CBP-1019 in Combination With FOLFOX +/- Bevacizumab, Pembrolizumab, or Enzalutamide for Metastatic TRPV6-overexpressing Solid Tumors of Epithelial Origin

NCT06576037 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2024-0474NCI-2024-07312
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

An open-label, Phase Ib dose escalation and dose expansion clinical trial evaluating the safety and efficacy of CBP-1019 combinations in patients with solid tumors of epithelial origin.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (8)

Part 1A: Dose Escalation CBP-1019 + FOLFOX

EXPERIMENTAL

Participants will be administered the study treatments on an outpatient basis.

Drug: CBP-1019; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-FLUOROURACIL

Part 1B: Dose Escalation CBP-1019 + FOLFOX + Bevacizumab

EXPERIMENTAL

Participants will be administered the study treatments on an outpatient basis.

Drug: CBP-1019; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-FLUOROURACIL; Drug: Bevacizumab

Part 1C: Dose Escalation CBP-1019 + Pembrolizumab

EXPERIMENTAL

Participants will be administered the study treatments on an outpatient basis.

Drug: CBP-1019; Drug: Pembrolizumab

Part 1D: Dose Escalation CBP-1019 + Enzalutamide

EXPERIMENTAL

Participants will be administered the study treatments on an outpatient basis.

Drug: CBP-1019; Drug: Enzalutamide

Part 2A: Pancreatic CBP-1019 + FOLFOX

EXPERIMENTAL

Participants will be administered the study treatments on an outpatient basis.

Drug: CBP-1019; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-FLUOROURACIL

Part 2B: Colorectal CBP-1019 + FOLFOX + Bevacizumab

EXPERIMENTAL

Participants will be administered the study treatments on an outpatient basis.

Drug: CBP-1019; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-FLUOROURACIL; Drug: Bevacizumab

Part 2C: Epithelial Origin CBP-1019 + Pembrolizumab

EXPERIMENTAL

Participants will be administered the study treatments on an outpatient basis.

Drug: CBP-1019; Drug: Pembrolizumab

Part 2D: CRPC CBP-1019 + Enzalutamide

EXPERIMENTAL

Participants will be administered the study treatments on an outpatient basis.

Drug: CBP-1019; Drug: Enzalutamide

Interventions

CBP-1019 DRUG

Given by vein (IV)

Part 1A: Dose Escalation CBP-1019 + FOLFOX; Part 1B: Dose Escalation CBP-1019 + FOLFOX + Bevacizumab; Part 1C: Dose Escalation CBP-1019 + Pembrolizumab; Part 1D: Dose Escalation CBP-1019 + Enzalutamide; Part 2A: Pancreatic CBP-1019 + FOLFOX; Part 2B: Colorectal CBP-1019 + FOLFOX + Bevacizumab; Part 2C: Epithelial Origin CBP-1019 + Pembrolizumab; Part 2D: CRPC CBP-1019 + Enzalutamide

Oxaliplatin DRUG

Given by vein (IV)

Part 1A: Dose Escalation CBP-1019 + FOLFOX; Part 1B: Dose Escalation CBP-1019 + FOLFOX + Bevacizumab; Part 2A: Pancreatic CBP-1019 + FOLFOX; Part 2B: Colorectal CBP-1019 + FOLFOX + Bevacizumab

Leucovorin DRUG

Given by vein (IV)

Part 1A: Dose Escalation CBP-1019 + FOLFOX; Part 1B: Dose Escalation CBP-1019 + FOLFOX + Bevacizumab; Part 2A: Pancreatic CBP-1019 + FOLFOX; Part 2B: Colorectal CBP-1019 + FOLFOX + Bevacizumab

5-FLUOROURACIL DRUG

Given by vein (IV)

Part 1A: Dose Escalation CBP-1019 + FOLFOX; Part 1B: Dose Escalation CBP-1019 + FOLFOX + Bevacizumab; Part 2A: Pancreatic CBP-1019 + FOLFOX; Part 2B: Colorectal CBP-1019 + FOLFOX + Bevacizumab

Bevacizumab DRUG

Given by vein (IV)

Part 1B: Dose Escalation CBP-1019 + FOLFOX + Bevacizumab; Part 2B: Colorectal CBP-1019 + FOLFOX + Bevacizumab

Pembrolizumab DRUG

Given by vein (IV)

Part 1C: Dose Escalation CBP-1019 + Pembrolizumab; Part 2C: Epithelial Origin CBP-1019 + Pembrolizumab

Enzalutamide DRUG

Given by mouth

Part 1D: Dose Escalation CBP-1019 + Enzalutamide; Part 2D: CRPC CBP-1019 + Enzalutamide

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 or cytologically confirmed malignancy of epithelial origin other than ovarian cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. Patients must have received at least one prior line of systemic standard therapy, and have either disease progression or intolerable toxicity after standard treatment.
• In the dose expansion, Regimen A will enroll patients with metastatic pancreatic cancer with concurrent oxaliplatin and irinotecan-free interval ≥4 months (Cohort 1), Regimen B will enroll patients with metastatic colorectal cancer concurrent oxaliplatin and irinotecan-free interval ≥4 months (Cohort 2), Regimen C will enroll patients with metastatic solid tumors of epithelial origin who have received prior anti-PD-(L)1 therapy (Cohort 3), and Regimen D will enroll patients with metastatic castration-resistant and taxane-treated prostate cancer (Cohort 4).
• Patients (with the exception of those with prostate cancer) 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 ≥10 mm (≥1 cm) with computed tomography (CT) scan,PET-CT, magnetic resonance imaging (MRI) scan, or calipers by clinical exam.
• Note: Prostate cancer patients must meet ≥1 of the following Prostate Cancer Clinical Trials Working Group 3 criteria \[95\]:
• Progression in measurable disease.
• Bone disease progression defined by the appearance of ≥2 new bone lesions.
• Prostate-specific antigen (PSA) progression defined as ≥2 sequential rises in PSA obtained ≥1 week apart with a minimal starting value of ≥1 ng/mL. A PSA value ≥2 ng/mL is required at study entry.
• Ability to understand and the willingness to sign a written informed consent document.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 (Appendix 1).
• Must have adequate organ and marrow functions as defined below:
• Absolute neutrophil count (ANC) ≥1.5× 109/L: growth factor support is not allowed within 2 weeks of study treatment initiation.
• Hemoglobin ≥9 g/dL: packed RBC transfusion is allowed as long as there is no active bleeding.
• Platelets ≥100× 109/L: transfusion is not allowed within 2 weeks of study treatment initiation.
• Total bilirubin ≤1.5× upper limit of normal (ULN); or total bilirubin \<3.0× ULN with direct bilirubin ≤ ULN in patients with well documented Gilbert's syndrome.

You may not qualify if:

• Has received an investigational non-myelosuppressive agent within 14 days prior to study treatment initiation or an investigational myelosuppressive agent within 21 days prior to study treatment initiation.
• Uncontrolled intercurrent illness including but not limited to:
• Ongoing or active infection requiring IV antibiotics.
• Symptomatic congestive heart failure (New York Heart Association Class III or IV).
• History of myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months before study enrollment.
• Lesions invading or encasing any major blood vessels and cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation; uncontrolled hypertension defined as sustained blood pressure \>140 mmHg systolic / \>90 mmHg diastolic despite optimal antihypertensive treatment (applies to bevacizumab-based regimen only).
• History or current evidence of uncontrolled ventricular arrhythmia.
• Congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death.
• Clinically significant bleeding or active gastric or duodenal ulcer.
• Chronic diarrhea disease considered to be clinically significant by the investigator.
• Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before the first dose of study treatment, or any GI disorders associated with a high risk of perforation or fistula formation.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
• Note: Patients with a diagnosis of incidental subsegmental pulmonary embolism or deep vein thrombosis are allowed if stable, asymptomatic, and on a stable dose of anticoagulant for at least 1 week before the first dose of study treatment.
• Unresolved clinically significant Grade ≥1 toxicity from prior therapy. Note: Patients who were exposed to prior treatment with any of the combination regimens that experienced intolerable or severe toxicity, even if they recovered; or who required dose reduction of chemotherapy or enzalutamide in their standard of care therapies should be excluded.
• History of allergic reactions to the study drugs or any of their components.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Interventions

Oxaliplatin; Leucovorin; Fluorouracil; Bevacizumab; pembrolizumab; enzalutamide

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Siqing Fu, MD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Siqing Fu, MD,PHD

CONTACT

(713) 792-4318; siqingfu@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: August 26, 2024
• First Posted: August 28, 2024
• Study Start: October 31, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2029
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)