Breast Cancer Metastatic, HER2 + Breast Cancer, Hormone Receptor-Positive Breast Cancer, Locally Advanced Breast Cancer (LABC), Malignant Neoplasm of Breast, Triple Negative Breast Cancer (TNBC)
Conditions
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
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.
Interventions
BIOLOGICALTwo Component Product CLBR001 + ABBV-461
Investigational switchable CAR-T cell therapy for breast cancer
Sponsors
Calibr, a division of Scripps Research
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with adverse events as assessed by CTCAE v5.0 and ASTCT consensus grading criteria for CRS and ICANS | To 1-year post administration of CLBR001 | 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. |
| Number of subjects with replication competent lentivirus | To 1-year post administration of CLBR001 | To assess the safety and tolerability in subjects by evaluating the number of subjects testing positive for replication competent lentivirus. |
| Number of dose-limiting toxicities as assessed by CTCAE v5.0 and ASTCT consensus grading for CRS and ICANS | To 28-days post-first dose of ABBV-461 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics | To 1-year post administration of CLBR001 | To measure pharmacodynamic response by evaluating concentrations of serum cytokines. |
| Assess Immunogenicity using Antidrug Antibodies | To 1-year post administration of CLBR001 | To determine Immunogenic response to CLBR001 and ABBV-461 by presence of antidrug antibodies (ADA) |
| Overall Best Objective Response | To 1-year post administration of CLBR001 | 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. |
| Disease Control Rate | To 1-year post administration of CLBR001 | To evaluate anti-tumor activity of CLBR001 + ABBV-461 by assessing Disease Control Rate by using RECIST v1.1. |
| Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : Cmax | To 1-year post administration of CLBR001 | 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. |
| Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : Tmax | To 1-year post administration of CLBR001 | 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. |
| Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : AUC | To 1-year post administration of CLBR001 | 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. |
| Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : t(1/2) | To 1-year post administration of CLBR001 | 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. |
Countries
United States
Contacts
STUDY_DIRECTORChief Medical Officer, MD
Calibr-Skaggs Institute for Innovative Medicines
Outcome results
None listed