Advanced Colorectal Cancer CAR T Cleared for Trial

The phase 1 portion of the trial assessing CNA3103 will start enrollment in Australia in the first half of 2023; the phase 2 portion will expand to the US.

Carina Biotech has received a “Safe to Proceed” letter for its investigational new drug application (IND) for its LGR5-targeted chimeric antigen receptor (CAR) T-cell therapy CNA3103 to be evaluated in a phase 1/2 trial in participants with advanced colorectal cancer.

“Our positive engagement with the FDA marks a major step forward for Carina and our continued efforts to develop CNA3103 as a potential treatment for the third most common cancer in the U.S. and worldwide, colorectal cancer,” Deborah Rathjen, chief executive officer, Carina Biotech, said in a statement. “The FDA’s letter provides the pathway for this clinical trial and further validates that a significant unmet need exists for more effective treatment options for colorectal cancer. Preparations, including site selection, are underway as we aim to commence enrolling patients during the first half of 2023.”

Carina is on track to commence patient enrollment in the study in the first half of 2023. The trial has a target enrollment of 44 participants with metastatic, advanced, LGR5-expressing colorectal cancer that has failed prior lines of chemotherapy. The phase 1 portion of the study will enroll 24 patients in select Australian centers, and, in a Bayesian Optimal Interval design will administer ascending CAR-T cell doses to cohorts of 3 patients each. The trial will assess the safety and tolerability of CNA3103 and determine the recommended phase 2 dose. The phase 2 portion of the study will enroll 20 more patients at the optimal dose in both Australia and the US and evaluate antitumor activity, duration of response, and time to disease progression in patients treated with CNA3103.

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CNA3103 targets LGR5, a cancer stem cell gene highly expressed on advanced colorectal cancer and other cancers, with a particularly poor prognosis associated with LGR5-expressing colorectal cancer. Carina hopes that the therapy’s targeting of cancer stem cells will suppress tumor growth and prevent relapses. Preclinical studies of CNA3103 have demonstrated complete tumor regression without recurrence after a single administration, with exceptional tumor access and prolonged survival.

“This interaction with the FDA corroborates our ability to gain the agency’s support for our proposed trial of CNA3103 in metastatic colorectal cancer patients,” José Iglesias, MD, chief medical officer, Carina Biotech, added to the statement. “Our approach is doubly innovative, in being one of the of emergent CAR-T treatment protocols in solid tumors and in utilizing a novel, and to our knowledge, unique CAR-T construct against LGR5 – an important cancer stem cell-associated antigen linked to the pathogenesis, dissemination, and treatment resistance of colorectal cancer.”

Carina Biotech receives FDA “Safe to Proceed” letter for IND application for phase 1/2a clinical trial of LGR5-targeted CAR-T cell therapy candidate for treatment of advanced colorectal cancer. News release. Carina Biotech. January 24, 2023.
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