Clinical trial NCT06878248: A Study to Assess CLBR001+ABBV-461 in Subjects With Locally Advanced or Metastatic Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Breast Cancer Metastatic
Locally Advanced Breast Cancer (LABC)
Malignant Neoplasm of Breast
Triple Negative Breast Cancer (TNBC)
Hormone Receptor-Positive Breast Cancer
HER2 + Breast Cancer
Keywords: breast cancer
CAR-T therapy
metastatic breast cancer
locally advanced breast cancer
malignant neoplasm of breast
Triple Negative Breast Cancer
hormone receptor positive breast cancer
Lead sponsor: Calibr, a division of Scripps Research
Sponsor class: OTHER
First posted: 2025-03-14
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of subjects with adverse events as assessed by CTCAE v5.0 and ASTCT consensus grading criteria for CRS and ICANS
timeFrame: To 1-year post administration of CLBR001
measure: Number of subjects with replication competent lentivirus
timeFrame: To 1-year post administration of CLBR001
measure: Number of dose-limiting toxicities as assessed by CTCAE v5.0 and ASTCT consensus grading for CRS and ICANS
timeFrame: To 28-days post-first dose of ABBV-461
Secondary outcomes:
measure: Pharmacodynamics
timeFrame: To 1-year post administration of CLBR001
measure: Assess Immunogenicity using Antidrug Antibodies
timeFrame: To 1-year post administration of CLBR001
measure: Overall Best Objective Response
timeFrame: To 1-year post administration of CLBR001
measure: Disease Control Rate
timeFrame: To 1-year post administration of CLBR001
measure: Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : Cmax
timeFrame: To 1-year post administration of CLBR001
measure: Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : Tmax
timeFrame: To 1-year post administration of CLBR001
measure: Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : AUC
timeFrame: To 1-year post administration of CLBR001
measure: Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : t(1/2)
timeFrame: To 1-year post administration of CLBR001
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Comprehensive Cancer Center
state: Indiana
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Calibr-Skaggs Institute for Innovative Medicines
name: Chan Beals, MD, PhD
role: STUDY_DIRECTOR
References: