Of the 8 treated patients who were evaluable, 6 patients had stable disease at Day 28.
IMC001, an investigational chimeric antigen receptor (CAR) T-cell therapy which targets the EpCAM protein, has demonstrated a favorable safety profile and promising anti-tumor activities in patients with advanced colorectal and gastric cancers, according to data from a phase 1 clinical trial (NCT05028933) presented at the European Society for Medical Oncology (ESMO) 2022 Congress, September 9-13, 2022 in Paris, France.
Of the 8 treated patients who were evaluable in the low and medium dose groups, 6 patients had stable disease at Day 28, and 1 of these patients achieved a partial response at week 32. All patients showed significant increases in cytokine levels, while circulating–tumor cells (CTC) in the blood decreased to 0 between 7 days and 4 weeks post-infusion. In terms of safety, all patients experienced grade 3 or greater hematologic toxicity, however no dose limiting toxicities (DLT) were reported. Common grade 3 and greater adverse events (AEs) included decreases in lymphocyte, leukocyte, and platelet counts. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in the patients treated.
As of the data cut-off, 6 participants, including 3 patients with colorectal cancers and 3 patients with gastric cancers, had received the low dose of 3×105 cells/kg of IMC001, while 1 patient with colorectal cancer and 1 patient with gastric cancer had received the medium dose of 1x106 cells/kg. In addition to the previously mentioned AEs, 1 patient experienced a serious case of immune hepatitis approximately 11 days post-infusion which prolonged the hospital stay, but ultimately resolved after symptoms were treated. One patient with colorectal cancer and 1 patient with gastric cancer experienced cases of grade 1 to 2 cytokine release syndrome (CRS), and 1 case of grade 3 CRS was reported in 1 gastric cancer patient. Additional treatment-related adverse events related to IMC001 included grade 1 to 2 cases of nausea, vomiting, asthenia, and pruritus, which were recovered from quickly.
“There is a bridging chemotherapy that occurred after leukapheresis,” Alessandra Curioni, MD, Center of Hematology and Oncology, University Hospital Zurich, said during an invited discussion of the study presentation, pointing out a limitation in the clinical trial’s design. “For how long and which [chemotherapy] has been used in this population of patients is not described... This might complicate when we have to look at the data and understand the response at the end to the treatment... In terms of the [change in the number of CTC] end point we have to keep in mind that there is probably 1 case with a deep decrease of CTC circulating, but this occurs already after day -5, before the product was given... Many factors might have also contributed to the response in the patients; as we said before there is a bridging chemotherapy, there is a lymphodepletion chemotherapy regimen before the infusion... This warrants further investigation.”
The ongoing open-label, multicenter trial is estimated to enroll 48 patients between the ages of 18 and 70 years. The first stage is a single dose escalation with 3 increasing dose levels: 3×105 cells/kg, 1×106 cells/kg, and 3×106 cells/kg. The second stage will combine the dose selected from stage 1 with radiofrequency or microwave ablation treatment. The first stage is open to patients with advanced gastric cancer, advanced colorectal cancer, advanced pancreatic cancer, or advanced liver cancer, while the second stage is open to patients with liver metastases of advanced gastric cancer, advanced colorectal cancer, or advanced pancreatic cancer. Patients in both stages must have been previously treated unsuccessfully with standard treatments and must not have any other feasible effective treatment methods available. All participants are required to have an Eastern Cooperative Oncology Group score of 0 to 1.
Participants are pretreated with fludarabine and cyclophosphamide before receiving IMC001 via an intravenous infusion. Primary end points include instances of DLTs, the maximum tolerated dose, and the incidence rate of AEs. Secondary end points include the duration of IMC001 cell persistence, objective response rate, progression-free survival, duration of response, overall survival, disease control rate, and the number of CTC in peripheral blood. The study’s estimated primary completion date is December 30, 2022 and its estimated completion date is December 31, 2024.
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