FDA Approves IND Application of IMC001 for EpCAM+ Gastrointestinal Tumors

• The FDA has cleared the investigational new drug application for IMC001 as a potential treatment option for patients with EpCAM-positive advanced gastrointestinal tumors.

• IMC001 is an investigational chimeric antigen receptor (CAR) T-cell therapy which targets the EpCAM protein.

• The agent has previously demonstrated a favorable safety profile and promising antitumor activity when used for the treatment of patients with advanced colorectal and gastric cancers.

The investigational new drug application of IMC001, an EpCAM-targeting autologous CAR T-cell therapy for infusion, has been accepted by the FDA for the treatment of patients with EpCAM-positive advanced gastrointestinal tumors, including gastric cancer, gastroesophageal junction (GEJ) adenocarcinoma, and more.¹

IMC001 works by targeting EpCAM. The agent is the first CAR T-cell therapy to aim to cure solid tumors by treating them as hematologic malignancies.

Encouraging results of IMC001 from a phase 1 clinical trial (NCT05028933) were shared during the European Society of Medical Oncology (ESMO) Annual Meeting in 2022 and updated during the American Society of Clinical Oncology (ASCO) Annual Meeting in 2023. Prior data from a trial evaluating IMC001 showed the agent to have an acceptable safety profile and to produce promising efficacy data.²

The phase 1, first-in-human, open-label trial involved 2 separate single-site trials, both of which followed a 3+3 design with dose escalation of 0.3, 1, or 3 million CAR T cells/kg following lymphodepletion chemotherapy. Patients with EpCAM-positive cancers were eligible for enrollment in the study if they had no further standard treatment options and had an ECOG performance status of 0 or 1.

Investigators sought to assess the safety, the pharmacokinetic and pharmacodynamic profile, and preliminary efficacy of IMC001.

In the investigator-initiated clinical trial which included patients with advanced gastric cancer, 2 of 5 patients achieved a partial remission (PR) and the overall response rate (ORR) was 40% as of January 31, 2024. Among those with a PR, 1 patient underwent a successful radical surgery for gastric cancer 30 weeks after a single infusion of IMC001. This patient is still alive 85 weeks after IMC001 treatment. Another patient with a PR had a 48% reduction in tumor size by week 16.

Gastric stomach cancer cells closeup view 3d illustration: © LASZLO - stock.adobe.com

For safety, no dose-limiting toxicities were seen within the 4-week follow-up visits after infusion. All patients experienced ≥ grade 3 hematologic toxicity, and 1 patient included in the low-dose group had a serious adverse event (AE) of grade 3 immune hepatitis. This serious AE may have been related to cell therapy.

Further, cytokine release syndrome was manageable at grades 1 to 3, and no cases of immune effector cell-associated neurotoxicity syndrome were observed. Other AEs deemed to be linked with cell therapy included CTCAE stage 1 to 2 nausea, vomiting, asthenia, or pruritus. All of these AEs resolved quickly.

Based on these findings, a safe and effective recommended dose has been identified and the trial is ongoing.

Previously, the product was granted an orphan drug designation from the FDA in August 2023.¹ Now, IMC001 marks the first EpCAM-targeted CAR T-cell product to gain investigational new drug approval by both the United States and China.

REFERENCES

1. Immunofoco announces the dual approval of IND applications by the U.S. FDA and China CDE for the first EpCAM CAR-T targeted at advanced solid tumors. News release. Immunofoco. February 22, 2024. Accessed February 26, 2024. http://tinyurl.com/yz3kcr7x

2. Luo T, Fang W, Lu Z, et al. EpCAM CAR T (IMC001) for the treatment of advanced GI cancers. J Clin Oncol. 2023;41(suppl 16):4034. doi:10.1200/JCO.2023.41.16_suppl.4034