KEY TAKEAWAYS
- The phase I trial aimed to report the results of low and middle-dosage groups in advanced gastric and GI cancer pts.
- The primary objective was to evaluate the safety, PK/PD profile, and preliminary efficacy of IMC001.
- The study showed favorable safety and anti-tumor activity in advanced EpCAM-positive GI cancers, especially gastric cancer, providing surgical opportunities in some pts.
EpCAM is a promising therapeutic target for gastrointestinal(GI) cancers, and IMC001 is an EpCAM-targeted CAR-T cell that showed promising anti-tumor activity in preclinical studies. Researchers aimed to report the results of low and middle-dosage groups in advanced gastric and GI cancers.
The study followed 2 single-site trials 3+3 design with dose escalation of 0.3, 1, or 3 million CAR-T cells/kg after chemotherapy with lymphodepletion. The first trial, CT03, focused on IMC001 monotherapy (Stage 1) for gastric cancer, while the second trial, CT04, included Stage 1 and examined the combination with RFA or microwave ablation (Stage 2) for GI cancers. Eligible patients(pts) had cancers with more than 10% EpCAM positivity, no further standard treatment options, and an ECOG performance status of 0 or 1. The primary objective was to evaluate the safety, pharmacokinetics/pharmacodynamics (PK/PD) profile, and preliminary efficacy of IMC001.
About 12 pts, evenly split between colorectal and gastric cancers, received 0.3 million or 1 million cells/kg of IMC001 infusion. No dose-limiting toxicity (DLT) occurred during the 4-week follow-up. All pts had severe hematologic toxicity, and one patient in the low-dose group experienced a serious adverse event (SAE) of immune hepatitis related to cell therapy, extending hospitalization. Mild to moderate cytokine release syndrome (CRS) was observed, but no immune effector cell-associated neurotoxicity syndrome (ICANS). Other cell therapy-related adverse events were mild and resolved quickly. CAR-T cells showed strong engraftment in all pts, peaking around day 5-7 post-infusion. Circulating tumor cells (CTC) remained undetectable for over 40 weeks. Most pts exhibited elevated levels of interleukin(IL)-6, IP-10, IFN-γ, IL-15, and MCP-1. Initial efficacy results revealed that 2 out of 6 advanced gastric cancer pts achieved partial responses (PR), while 3 maintained stable disease (SD) by RECIST 1.1 criteria with low to middle dosages (CT03).
The first PR patient received a second IMC001 infusion at week 50 and survived for over 60 weeks. The second PR patient had successful stomach removal surgery 28 weeks after the IMC001 infusion. The CT04 trial is currently in progress.
The study showed favorable safety and anti-tumor activity in advanced EpCAM-positive GI cancers, especially gastric cancer, providing surgical opportunities in some patients.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.4034?role=
Clinical Trial: https://www.clinicaltrials.gov/study/NCT05028933
Tianhang Luo, Weijia Fang, Zhengmao Lu, Chuchu Tong, Hangyu Zhang, Guoqiang Ai, and Suqiong Wang. DOI: 10.1200/JCO.2023.41.16_suppl.4034 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 4034-4034.
