CARsgen Gets IND Clearance for GPC3-Targeted CAR for Hepatocellular Carcinoma


Three of CARsgen’s CAR therapies are currently on clinical hold due to CMC questions.

CARsgen has received investigational new drug (IND) clearance for its GPC3-targeted chimeric antigen receptor (CAR) T-cell therapy CT011 to initiate a clinical trial for patients with GPC3-positive stage IIIa hepatocellular carcinoma who are at high risk of recurrence after surgical resection.1

“Hepatocellular carcinoma (HCC) stands as the predominant histologic subtype of primary liver cancer, ranking as the sixth most prevalent cancer type globally. We initially identified GPC3 as a viable target for CAR T-cell therapy and subsequently progressed it to clinical trials for the treatment of HCC. Case report has shown patients with advanced hepatocellular carcinoma have achieved disease-free survival for more than 7 years,” Raffaele Baffa, MD, PhD, Chief Medical Officer of CARsgen Therapeutics, said in a statement.1 “We will continue to explore the potential of CAR-T for solid tumors and bring new treatment options for patients.”

CT011 is an autologous CAR T-cell therapy that previously received IND clearance in China. CARsgen has completed enrollment of a phase 1 trial in China.

Last month, CARsgen also announced IND clearance for its GPRC5D-targeted CAR T-cell therapy CT071 for the treatment of patients with relapsed/refractory multiple myeloma (MM) or relapsed/refractory primary plasma cell leukemia (PCL).2 CT071 incorporates a fully-human single-chain variable fragment developed by CARsgen to target GPRC5D.CT071 is manufactured with the company’s proprietary CARcelerate platform, which shortens the manufacturing time to less than 2 days, may yield younger, healthier, and possibly more potent CAR T cells compared to conventional manufacturing, and therefore enhance manufacturing capacity.

READ MORE: TCR-T Therapy Yields Some Responses in HBV-Related Hepatocellular Carcinoma

An investigator-initiated trial is already under way in China to assess the safety and efficacy of CT071 in patients with relapsed/refractory MM or PCL (NCT05838131). Preliminary clinical data from the trial shows an acceptable safety profile with preliminary efficacy.

In less positive news, CT071, along with CT053, also known as zevorcabtagene autoleucel (zevor-cel), and CT041, were placed on clinical hold by the FDA later in December due to chemistry, manufacturing, and controls-related concerns that arose after an FDA inspection of the company’s manufacturing facility in Durham, North Carolina.3

CARsgen said in its notice of the clinical hold to the Hong Kong Stock Exchange that it plans to conduct a comprehensive review and improve its Current Good Manufacturing Practices (cGMP) at the facility and 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.”3

The announcement came shortly after CARsgen presented data on zevor-cel from the phase 1b LUMMICAR study 1 (NCT03975907) conducted in China in patients with relapsed/refractory multiple myeloma (r/r MM) at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California.

As of July 17, 2023, the median survival follow-up duration was 37.7 months (range, 14.8-44.2), overall response rate was 100% (95% CI, 76.8-100.0), and 11 (78.6%) patients achieved complete response (CR) or stringent complete response (sCR). Two (14.3%) patients achieved very good partial response and 1 (7.1%) patient had partial response. All patients experienced treatment-related adverse events and grade 3 or 4 hematologic toxicity. Thirteen patients (92.9%) had cytokine release syndrome, all cases of which were grade 1 or 2.4

1. CARsgen’s CT011 achieves IND clearance from the NMPA for the GPC3-positive stage Ⅲa hepatocellular carcinoma at high risk of recurrence after surgical resection. News release. January 15, 2024.
2. CARsgen's CT071 received IND clearance from the FDA for treating relapsed/refractory multiple myeloma or relapsed/refractory primary plasma cell leukemia. News release. December 4, 2023.
3. Inside information announcement clinical hold in the U.S. due to CMC related questions. CARsgen. Letter.
4. Fu C, Chen W, Cai Z, et al. Three-Year Follow-up on Efficacy and Safety Results from Phase 1 Lummicar Study 1 of ZevorcabtageneAutoleucel in Chinese Patients with Relapsed or Refractory Multiple Myeloma. Presented at: ASH 2023 Annual Meeting & Exposition. December 9-12; San Diego, CA. Abstract 4845.
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