Glioblastoma CAR-T Trial Completes Initial Follow-up of Third Dose Cohort

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No dose-limiting toxicities were observed at 28 days of follow-up.

A phase 1a clinical trial for Chimeric Therapeutics’ CHM 1101 (CLTX CAR T), an autologous investigational chimeric antigen receptor T-cell (CAR-T) therapy being evaluated for the treatment of MMP2-positive recurrent/progressive glioblastoma, has reached 28 days of follow-up for all patients dosed in its third cohort, with no dose-limiting toxicities (DLTs) reported.1

CHM 1101 utilizes a chlorotoxin (CLTX) tumor-targeting domain, which is derived from deathstalker scorpion venom.1,2 The therapy was licensed by Chimeric Therapeutics from City of Hope National Medical Center, which developed it.1,3 The 3 patients in the trial’s third cohort received CHM 1101 at a total dose of 240x106, with half of the dose delivered by intratumoral (ICT) administration and half of the dose delivered by intracerebroventricular (ICV) administration.1,4 Chimeric Therapeutics announced that the trial will advance to the dosing of patients in its fourth and last cohort. Patients in the fourth cohort will be treated with a total dose of 440x106 cells, split across the same routes of ICT and intraventricular ICV administration.

Data from patients in the trial’s second dose cohort, who received a total dose of 88x106 cells, were announced in February 2022.3 Chimeric Therapeutics noted that the administration of the therapy was generally well tolerated in this cohort, and that 2 of the 3 treated patients achieved local disease stability.

“This preliminary data is encouraging as it demonstrates safety with dual routes of administration,” Behnam Badie, MD, professor and chief, Division of Neurosurgery; director, Brain Tumor Program, Department of Surgery, City of Hope, said in a February 2022 statement.3 “We now look forward to advancing the trial to higher dose levels which may provide more therapeutic benefit to patients."

Earlier, in November 2021, the company presented data from the trial’s first cohort.2 The first cohort included 4 patients who received 44x106 cells via the ICT route of administration only. Among these patients, 3 achieved stable disease. It was additionally reported that the CHM 1101 cells persisted in the tumor cavity throughout treatment, indicating non-immunogenicity, and that the therapy was generally well tolerated in this cohort. A case of grade 3 edema occurred, which was deemed “possibly” related to CHM 1101; however, it was noted that cerebral edema is a common adverse event in patients with glioblastoma. Furthermore, a correlation between expression of MMP2 on tumor cells and binding with CLTX was observed, indicating that MMP2 positivity may be able to function as an indicator of response for the therapy.

The phase 1a study is expected to enroll 18 to 36 patients in total across the 4 dose cohorts.1 A phase 1b clinical trial (NCT05627323), which has an estimated enrollment of 42 patients, is planned, but the initiation of recruitment has not yet been announced. Chimeric Therapeutics noted that it may explore CLTX CAR-T therapy for additional solid tumor indications, beginning with metastatic melanoma.

REFERENCES
1. Successful completion of 28-day follow up period for 3rd patient cohort in brain cancer phase 1 trial. News release. Chimeric Therapeutics. January 23, 2023. Accessed January 23, 2023. https://chimerictherapeutics.com/wp-content/uploads/2023/01/Follow-up-Period-completed-for-3rd-Cohort-in-CHM1101-Trial-23-Jan-2023.pdf 
2. CHM 1101(CLTX CAR T) phase 1 initial data release. Webinar. Chimeric Therapeutics. November 2021. Accessed January 23, 2023. https://chimerictherapeutics.com/wp-content/uploads/2021/11/CHM-1101-CLTX-CAR-T-Phase-1-Initial-Data-Release-Presentation.pdf
3. Encouraging data reported for 2nd dose cohort in CLTX CAR T trial. News release. Chimeric Therapeutics. February 8, 2022. Accessed January 23, 2023. https://chimerictherapeutics.com/wp-content/uploads/2022/02/2nd-CLTX-Cohort-COH-FINAL.pdf 
4. Completion of dosing in 3rd dose cohort in CHM 1101 (CLTX CAR T) clinical trial. News release. Chimeric Therapeutics. December 22, 2022. Accessed January 23, 2023. https://chimerictherapeutics.com/wp-content/uploads/2022/12/Completion-of-Dosing-in-3rd-Dose-Cohort-in-CHM-1101-CLTX-CAR-T-Clinical-Trial-22-Dec-2022.pdf
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