The company has initiated the world’s first confirmatory phase 2 trial of a CAR T-cell therapy in solid tumors.
CARsgen has completed patient enrollment in the phase 2 LUMMICAR STUDY 1 (NCT03975907) of CT053 (zevor-cel) and initiated a confirmatory phase 2 trial of CT041, marking the first of its kind trial of chimeric antigen receptor (CAR) T-cell therapies in solid tumors.1
Both autologous CAR T-cell therapies, Zevor-cel is a BCMA-targeted therapy for the potential treatment of relapsed/refractory multiple myeloma (rrMM) and CT041 is a CLDN18.2-targeted therapy being evaluated in advanced gastric cancer.
For zevor-cel, the company plans to submit the new drug application (NDA) to the National Medical Products Administration (NMPA) in the third quarter of 2022. CARsgen is also evaluating zevor-cel in rrMM in LUMMICAR STUDY 2 (NCT03915184) in North America and plans to submit a biologics license application to the FDA by the end of 2023. Additional trials are planned to evaluate zevor-cel as an earlier line of treatment for rrMM.
“For CT053, we plan to submit the NDA to the NMPA in the third quarter of 2022. Our US CGMP manufacturing facility has also started operations. We continue to dedicate ourselves to advancing innovative CAR T technologies to address the major challenges of the industry. We have also established in-house, vertically integrated manufacturing capabilities... we expect to bring innovative and differentiated cell therapy to cancer patients around the world as soon as possible, creating value for investors and the public,” Zonghai Li, PhD, chairman of the board, chief executive and chief scientific officer, CARsgen Therapeutics, said in a company update.1
CT053 uses a CAR construct with a fully human BCMA-specific single-chain variable fragment designed to have lower immunogenicity and increased stability. CARsgen hopes the therapy will address challenges of T-cell exhaustion by reducing self-activation of CAR T-cells when tumor-associated targets are not present. The therapy has received regenerative medicine advanced therapy (RMAT) and orphan drug designation (ODD) from the FDA; PRIority Medicine (PRIME) and orphan medicinal product (OMP) designation from the EMA; and breakthrough therapy designation from the NMPA.
Data from investigator-initiated trials (NCT03302403, NCT03380039, NCT03716856) on zevor-cel were published in Haematologica in July 2022.2 These data demonstrated that the therapy was tolerable, with no serious (above grade 3) treatment-related adverse events.
Across trials, at a cutoff date of June 30, 2021, and at a median follow-up time of 17.4 months (range, 0.9-38.7), overall response rate (ORR) was 87.5%, with 79.2% of patients experiencing a complete response (CR, 12.5) or stringent complete response (66.7). CR/stringent CR rate was 70% for patients with extramedullary disease and 8% for patients without. Median progression-free survival (PFS) was 18.8 months (95% CI, 10.1-not estimable [NE]) in all patients and median overall survival (OS) was not reached. Median duration of response was 21.8 months (95% CI, 9.2-NE) in all patients.
On the solid tumor front, CT041 is now being investigated in the confirmatory phase 2 clinical trial (CT041-ST-01; NCT04581473) in China in advanced gastric cancer.1 It is also being investigated in a phase 1b/2 trial in North America (CT041-ST-02; NCT04404595). CARsgen plans to initiate a phase 2 trial in North America in the second half of 2022, submit an NDA to the NMPA in the first half of 2024, and to submit a BLA to the FDA in 2024. CT041 has received ODD, RMAT, OMP, and PRIME designations.
“CT041 has become the world's first and the only CAR T-cell candidate for the treatment of solid tumors entering a confirmatory Phase II clinical trial,” Li added to the update.1
CARSgen presented updated data on CT041 at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting in June 2022 from the phase 1b/2 trial as well as the phase 1 part of the confirmatory trial.3 The data showed that 8 of 14 patients (57.1%) had a partial response at the first tumor assessment after infusion. ORR was 57.1% and disease control rate was 78.6%. With a median follow-up of 8.8 months, median PFS was 5.6 months and OS was 10.8 months, with 7 patients surviving by the cutoff date. One patient had grade 4 cytokine release syndrome.