FDA Grants GCC19CART Fast Track Designation for Colorectal Cancer

The FDA has granted a Fast Track Designation to GCC19CART as a potential treatment for patients with relapsed and refractory metastatic colorectal cancer (mCRC), according to a statement from Innovative Cellular Therapeutics (ICT), the developer of the guanylate cyclase 2C (GCC)-targeted autologous CAR T-cell therapy.

The Fast Track Designation is meant to facilitate and expedite the development of treatments for serious conditions that fill an unmet need. With the mCRC designation, ICT will benefit from more frequent interaction with the FDA. Additionally, if clinical studies are successful, the company will be eligible for an accelerated approval, priority review, and the ability to submit a rolling biologic license application.

“We are pleased that GCC19CART has received FDA Fast Track Designation highlighting the large unmet need in patients with relapsed or refractory colorectal cancer,” Larry (Lei) Xiao, PhD, ICT’s founder and chief executive officer, said in a statement. “GCC19CART is our lead solid tumor product candidate from our CoupledCAR platform technology that has shown early promising clinical results in China. We are now focusing our efforts on its development in the US.”

GCC19CART was designed using ICT's CoupledCAR platform, which combines 2 CAR T cells engineered to release cytokines that are thought to promote proliferation and infiltration. The platform was designed following observations that CD19-directed CAR T cells also stimulated the immune system, which could lead to increase proliferation for other CAR T cells, specifically those directed toward solid tumor antigens, like GCC.

The treatment follows a step wise approach, wherein CD19 CAR T cells kill B cells causing the release of a signaling molecule that activates and causes the proliferation of the solid tumor-specific CAR T cells, even without the presence of the solid tumor target antigen. The company theorized this approach would be more effective in solid tumors, which tend to have less circulating tumor antigen compared with hematologic malignancies.

The GCC-targeted CoupledCAR therapy GCC19CART is the furthest along in the ICT pipeline. The company noted that it had run an Institutional Review Board (IRB)-approved clinical study in China that enrolled 35 patients with mCRC. In this study, GCC19CART at a dose of 2 x 10^6 cells per kg was given to 8 patients who had received at least 2 prior lines of therapy before entering the study. In this heavily pretreated group of patients, the company said the overall response rate (ORR) was 50% with GCC19CART.

In the United States, an Investigational New Drug (IND) was approved in September 2021 to explore GCC19CART for patients with R/R mCRC. The phase 1 study, known as CARAPIA-1, is not yet recruiting participants but is expected to start enrolling within the first half of 2022.

“This IND clearance builds upon the promising clinical data generated by our team in Shanghai demonstrating objective responses with manageable expected toxicity when administered to heavily pretreated colorectal cancer patients as single-agent experimental therapy,” Eugene Kennedy, MD, chief medical officer of ICT, said when the IND was approved in September. “I look forward to advancing this program in the US while we continue to develop proof-of-concept data for additional solid tumor indications.”

The phase 1 study plans to enroll 30 participants with R/R mCRC, which will explore escalating doses of GCC19CART in a 3+3 schema (NCT05319314). The primary end points of the escalation portion of the study are focused on the adverse events, dose-limiting toxicities, maximum tolerable dose, and the discovery of a recommended phase 2 dose. Secondary outcome measures will focus on response, duration of response, progression-free survival, overall survival, and biomarker measures, including GCC and CD19 copy number changes by PCR and IL-6, IL-12, IFN-γ levels by ELISA.

“Because GCC19CART and all future product candidates from our CoupledCAR platform share key aspects of technology and manufacturing, we believe the IND clearance is a first step towards validation of not only GCC19CART, but the potential of the entire platform,” Xiao, said when the IND was approved. “Indeed, we are advancing an extensive product candidate pipeline individually targeting multiple solid tumor indications. We are excited by the potential of our CoupledCAR platform based therapeutic candidates to address the significant unmet need of patients with advanced colorectal cancer and other solid tumors.”

In addition to mCRC, the ICT pipeline contains several other preclinical products and those in IRB-approved trials in China. These agents are being explored across several solid tumors and include targets such as TSHR in thyroid cancer, MSLN for pancreatic, bile duct, and lung cancers, GPC3 for liver cancer, PAP for prostate cancer, and ALPP for testicular and ovarian cancer. In addition to these, several other undisclosed targets are also in early development for other solid tumors.

REFERENCES:

• Innovative Cellular Therapeutics Receives FDA Fast Track Designation for GCC19CART, its Lead Solid Tumor Candidate, in the Treatment of Patients with Relapsed or Refractory Metastatic Colorectal Cancer. Innovative Cellular Therapeutics. April 19, 2022. https://www.ictbio.com/news/innovative-cellular-therapeutics-ict-receives-fda-fast-track-designation-for-gcc19cart-its-lead-solid-tumor-candidate-in-the-treatment-of-patients-with-relapsed-or-refractory-metastatic-colorectal/

• ICT Receives FDA Clearance of IND Application to Initiate a Phase 1 Clinical Trial for GCC19CART. September 1, 2021. https://www.ictbio.com/news/innovative-cellular-therapeutics-receives-fda-clearance-of-ind-application-to-initiate-a-phase-1-clinical-trial-for-gcc19cart-a-coupledcar-platform-product-candidate-for-relapsed-or-refractory/