FDA Removes Clinical Holds Previously Placed on 3 of CARsgen's Oncology Cell Therapies

The FDA has removed clinical holds from the phase 1b/2 LUMMICAR 2 clinical trial (NCT03915184) evaluating CARsgen's BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapy zevorcabtagene autoleucel(zevor-cel) for relapsed/refractory (r/r) multiple myeloma (MM), the phase 1b/2 ELIMYN18.2 (ST-02) clinical trial (NCT04404595) evaluating its Claudin18.2-directed CAR-T satricabtagene autoleucel(satri-cel) for gastric/pancreatic cancers, and a phase 1/2 clinical trial (NCT06333509) evaluating its GPRC5D-directed CAR-T CT071 for r/r MM and r/r primary plasma cell leukemia.¹

The clinical holds on the 3 products were originally placed by the FDA in December 2023 based on chemistry, manufacturing, and controls (CMC)-related questions that arose from findings of an inspection of CARsgen’s manufacturing facility in Durham, North Carolina, according to a notice the company provided to the Hong Kong Stock Exchange on December 12, 2023.² At the time, the company stated that it planned to conduct a comprehensive review and improve its current Good Manufacturing Practices (cGMP) at the facility, noting that it is “committed to working closely with the FDA to address the findings to ensure the smooth progress and production quality for clinical trials and launching applications.”¹

Notably, zevor-cel was approved by China’s National Medical Products Administration in March 2024 for the treatment of adult patients with r/r MM whose disease progressed after at least 3 lines of therapy, including treatment with a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD).³ The NMPA's regulatory decision was supported by data from the phase 1/2 LUMMICAR STUDY 1 trial (NCT03975907), which showed that at a median follow-up of 37.7 months (range, 14.8-44.2), evaluable patients treated with the BCMA-targeted CAR T-cell therapy (n = 14) achieved an overall response rate (ORR) of 100% and a complete response (CR)/stringent CR (sCR) rate of 78.6%.⁴ Notably, all patients who experienced a CR/sCR achieved minimal residual disease negativity.

“In the realm of traditional treatments, the prognosis for patients dealing with relapsed or refractory multiple myeloma remains notably grim, given the limitations of available therapeutic alternatives."

“These individuals confront substantial unmet clinical needs, necessitating an expeditious adoption of an effective, safe, and convenient treatment modalities,” Wenming Chen, MD, PhD, principal investigator of LUMMICAR STUDY 1 and director of the Hematology Department at Beijing Chao-Yang Hospital of Capital Medical University in China, said in a March 2024 statement.³ “The approval of zevor-cel not only expands the array of choices available to clinical practitioners but also brings new hope to patients.”

CGTLive® has previously provided coverage of the ELIMYN18.2 clinical trial, which is evaluating satri-cel in heavily pretreated Claudin18.2 (CLDN18.2)-positive advanced gastric/gastroesophageal (GC/GEJ) or pancreatic cancer (PC). The ELIMYN18.2 trial is evaluating the safety and efficacy of satri-cel in patients with advanced GC/GEJ or PC whose disease had progressed or was unresponsive to at least 2 prior lines (GC/GEJ) or 1 prior line (PC) of systemic therapy.

“This is worldwide the first CLDN18.2 program that has received multiple countries’ investigational new drug (IND) clearance... the program is also the first solid tumor CAR-T program that has received multiple designations [from regulatory agencies,” Hong Ma, MD, Sr. Vice President of Clinical Development for Cancer Immunotherapy, CARsgen, told CGTLive.“The next step, for gastric cancer, we shouldn't consider whether it can be moved to the early line, because solid tumors is very difficult to treat and gastric cancer is probably one of the most difficult to treat cancers. The results are promising but it is last line, and we hope the early line we want to test and see if there's a potential to cure the cancer.”

REFERENCES
1. CARsgen U.S. clinical holds lifted by FDA. News release.CARsgen Therapeutics Holdings Limited. November 1, 2024. Accessed November 7, 2024. https://www.carsgen.com/en/news/carsgen-u-s-clinical-holds-lifted-by-fda/
2.Inside information announcement clinical hold in the U.S. due to CMC related questions. CARsgen. Letter. December 12, 2023. Accessed November 7, 2024. https://www1.hkexnews.hk/listedco/listconews/sehk/2023/1212/2023121201146.pdf
3. NMPA Approves the NDA for CARsgen's BCMA CAR-T therapy zevorcabtageneautoleucel for relapsed or refractory multiple myeloma. News release. CARsgen Therapeutics. March 1, 2024. Accessed November 7, 2024. https://www.carsgen.com/en/news/20240301/
4. CARsgen presents updated research results on zevor-cel at 2023 ASH Annual Meeting. News release. CARsgen Therapeutics. December 12, 2023. Accessed November 7, 2024. https://www.carsgen.com/en/news/20231212/