Calibr-Skaggs doses first patient with switchable CAR-T cell therapy in a phase 1 trial for metastatic breast cancer

The Calibr-Skaggs Institute for Innovative Medicines, the drug development division of Scripps Research, today announced a milestone in cancer treatment with the dosing of the first patient in a phase 1 trial (NCT06878248) evaluating CLBR001 + ABBV-461, a modular, switchable chimeric antigen receptor T cell (sCAR-T) therapy in patients with advanced or metastatic breast cancer who have no suitable treatment options. This is the first study of the sCAR-T platform in solid tumors.

CAR-T therapy has been transformative for patients with hematologic malignancies who failed numerous prior treatments. However, conventional CAR-T therapies have not yet been as successful at treating patients with solid tumors. This challenge is what Calibr-Skaggs' switchable CAR-T cell therapy platform was designed to address.

The sCAR-T platform developed by Calibr-Skaggs is designed to enhance the precision and safety of CAR-T therapies, and has demonstrated promising preliminary results in a phase 1 clinical trial for hematologic malignancies. Additionally, initial results have demonstrated CLBR001 sCAR-T cells can expand in the body in significantly greater numbers than conventional CAR-T cells, affording a better chance of penetrating the hostile solid tumor microenvironment. And the switch offers an added advantage by allowing the cells to "rest," potentially avoiding CAR-T exhaustion.

"There's a critical need to develop gene and cell therapy approaches that are able to recreate the success observed in blood cancers for patients with solid tumors like breast cancer," said Travis Young, Ph.D., vice president of biology at Calibr-Skaggs. "By integrating an antibody-based 'switch,' there's the potential to enhance the precision of targeting solid tumor cells, while also mitigating potential safety risks."

The clinical trial testing CLBR001 + ABBV-461 is now underway in the US. CLBR001 + ABBV-461 is being developed in collaboration with AbbVie.

About phase 1 clinical trial

NCT06878248 is 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 goals are to establish the safety and efficacy of the two-part therapy while establishing optimal biologic switch doses. Patients will be administered a single infusion of CLBR001 cells post lymphodepletion followed by cycles of ABBV-461 switch with regular assessments of safety and disease response to treatment.

About Calibr-Skaggs' sCAR-T platform

This platform uses a unique two-component system: an engineered T cell product (CLBR001) and an antibody-based drug—the 'switch.' The switch binds to both the target antigen on tumor cells and the CLBR001 cells, effectively "switching on" the CLBR001 cells to eliminate the cancerous cells, which is like a remote control for physicians. This design feature provides potential efficacy advantages and also safety optionality, as the physician can pause dosing of the switch in the case of an adverse event.

Provided by The Scripps Research Institute