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

Phase 1RecruitingNCT06878248

Calibr, a division of Scripps Research20 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Breast Cancer Metastatic Locally Advanced Breast Cancer (LABC)Malignant Neoplasm of Breast

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (4)

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, United States

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: To 28-days post-first dose of ABBV-461

Secondary Outcomes

Pharmacodynamics

To measure pharmacodynamic response by evaluating concentrations of serum cytokines.

Time frame: 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)

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: To 1-year post administration of CLBR001

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

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts