A Study to Assess CLBR001+ABBV-461 in Subjects With Locally Advanced or Metastatic Breast Cancer

A Phase 1, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Combination of CLBR001, an Engineered Autologous T Cell Product, and ABBV-461, an Antibody-Based Biologic, in Subjects With Locally Advanced or Metastatic Breast Cancer

The goal of this clinical trial is to evaluate CLBR001 and ABBV-461 as a treatment for patients with locally advanced or metastatic breast cancer. The goals are to establish the safety and efficacy of the combination therapy while establishing the optimal biologic doses.

Patients will be administered a single infusion of CLBR001 cells followed by cycles of ABBV-461 with regular assessments of safety and disease response to treatment.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer Metastatic; Malignant Neoplasm of Breast; Triple Negative Breast Cancer (TNBC); Hormone Receptor-Positive Breast Cancer; Locally Advanced Breast Cancer (LABC); HER2 + Breast Cancer
• Intervention / Treatment: Biological: Two Component Product CLBR001 + ABBV-461

Detailed Description

CLBR001 + ABBV-461 is novel switchable CAR-T cell combination therapy comprised of an autologous CAR-T product (CLBR001, the switchable CAR-T cell [sCAR-T]) and ABBV-461 (the "switch" biologic molecule). ABBV-461 acts as an adapter molecule that controls the activity of the CLBR001 CAR-T cell product.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Comprehensive Cancer Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Refractory or relapsed locally advanced or metastatic breast cancer
• Exhaused all standard of care therapy options
• Measurable disease at time of screening in accordance with RECIST v1.1 criteria
• Women or men age ≥18 years of age at time of consent
• ECOG performance status 0 or 1
• Must provide a biopsy sample obtained during the screening period, following the end of the most recent prior line of therapy
• Adequate hematological, renal, and liver function

Exclusion Criteria:

• History of a clinically significant infection within 4 weeks prior to consent
• Active bacterial, viral, and/or fungal infection
• Prior allogeneic stem cell transplant
• Prior lentiviral- or retroviral-based therapy including CAR-T cell therapy
• Prior lymphodepleting or T-cell cytotoxic therapy within 3 months of enrollment
• Subjects receiving attenuated vaccines within 4 weeks of consent or need for live vaccine within 12 months of starting study therapy
• History of significant cardiovascular conditions within the past 6 months
• Subjects with a prior history of or concurrent malignancy whose natural history or treatment has the potential to interfere with either the safety or efficacy assessment of the investigational regimen

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Combination product CLBR001 + ABBV461 is administered in ascending dose level cohorts to determine the Optimal Biologic Dose (OBD) of CLBR001 + ABBV-461.	Biological: Two Component Product CLBR001 + ABBV-461; Investigational switchable CAR-T cell therapy for breast cancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with adverse events as assessed by CTCAE v5.0 and ASTCT consensus grading criteria for CRS and ICANS	To assess the safety and tolerability in subjects by evaluating the frequency, relatedness, severity and duration of adverse events, as assessed by CTCAE v5.0 and ASTCT consensus grading criteria for CRS and ICANS.	To 1-year post administration of CLBR001
Number of subjects with replication competent lentivirus	To assess the safety and tolerability in subjects by evaluating the number of subjects testing positive for replication competent lentivirus.	To 1-year post administration of CLBR001
Number of dose-limiting toxicities as assessed by CTCAE v5.0 and ASTCT consensus grading for CRS and ICANS	The number of dose-limiting toxicities as assessed by CTCAE v5.0 and ASTCT consensus grading for CRS and ICANS will be used to identify an Optimal Biologic Dose (OBD) of CLBR001 and ABBV-461.	To 28-days post-first dose of ABBV-461

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics	To measure pharmacodynamic response by evaluating concentrations of serum cytokines.	To 1-year post administration of CLBR001
Assess Immunogenicity using Antidrug Antibodies	To determine Immunogenic response to CLBR001 and ABBV-461 by presence of antidrug antibodies (ADA)	To 1-year post administration of CLBR001
Overall Best Objective Response	To evaluate anti-tumor activity of CLBR001 + ABBV-461 by assessing Overall (best) objective response by response evaluation criteria in solid tumors by using RECIST v1.1.	To 1-year post administration of CLBR001
Disease Control Rate	To evaluate anti-tumor activity of CLBR001 + ABBV-461 by assessing Disease Control Rate by using RECIST v1.1.	To 1-year post administration of CLBR001
Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : Cmax	To evaluate the pharmacokinetics (PK) of CLBR001, including expansion and persistence, and ABBV-461 by quantifying CLBR001 cells in peripheral blood and PK parameters of ABBV-461.	To 1-year post administration of CLBR001
Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : Tmax	To evaluate the pharmacokinetics (PK) of CLBR001, including expansion and persistence, and ABBV-461 by quantifying CLBR001 cells in peripheral blood and PK parameters of ABBV-461.	To 1-year post administration of CLBR001
Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : AUC	To evaluate the pharmacokinetics (PK) of CLBR001, including expansion and persistence, and ABBV-461 by quantifying CLBR001 cells in peripheral blood and PK parameters of ABBV-461.	To 1-year post administration of CLBR001
Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : t(1/2)	To evaluate the pharmacokinetics (PK) of CLBR001, including expansion and persistence, and ABBV-461 by quantifying CLBR001 cells in peripheral blood and PK parameters of ABBV-461.	To 1-year post administration of CLBR001

Collaborators and Investigators

• Sponsor: Calibr, a division of Scripps Research
• Investigators: Study Director: Chief Medical Officer, MD, Calibr-Skaggs Institute for Innovative Medicines

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2025
• Primary Completion (Actual): April 9, 2026
• Study Completion (Actual): April 9, 2026

Study Registration Dates

• First Submitted: March 6, 2025
• First Submitted That Met QC Criteria: March 11, 2025
• First Posted (Actual): March 14, 2025

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer; Triple Negative Breast Cancer; metastatic breast cancer; locally advanced breast cancer; hormone receptor positive breast cancer; CAR-T therapy; malignant neoplasm of breast
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: CBR-sCAR461-3001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No