On January 29, 2020 Unum Therapeutics Inc. (NASDAQ: UMRX), a clinical-stage biopharmaceutical company focused on developing curative cell therapies for cancer, reported it has completed Cohort 1 enrollment with no dose-limiting toxiticies (DLT) observed in the ATTCK-34-01 Phase 1 trial evaluating Unum’s novel Antibody-Coupled T cell Receptor investigational therapy, ACTR707, together with trastuzumab for the treatment of patients with HER2+ advanced cancers (Press release, Unum Therapeutics, JAN 29, 2020, View Source [SID1234553640]).
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Patient enrollment—defined as patients who have signed informed consent forms and met all eligibility criteria—is complete with five patients in this first cohort in the ATTCK-34-01 Phase 1 trial, a multicenter, open-label, single-arm, dose-escalation trial. Of the five patients enrolled, three patients received treatment with trastuzumab (1.0 mg/kg weekly) followed by administration of ACTR707 (25 million ACTR707+ T cells) and completed the DLT review period—defined as approximately six weeks post-ACTR707 administration—with no DLTs observed. Two patients enrolled but discontinued from the trial prior to receiving treatment with trastuzumab and ACTR707. In addition to safety and clinical response assessments, data on ACTR707+ T cell expansion and persistence, trastuzumab pharmacokinetics, and post-treatment biopsy analyses are being collected and are expected to inform subsequent dose escalation. Unum continues to plan to submit data from this Cohort for presentation at a scientific conference in 2020. Investigators have begun screening patients for Cohort 2 that includes treatment with trastuzumab (1.0 mg/kg weekly) followed by administration of ACTR707 (50 million ACTR707+ T cells).
"Understanding the significant unmet need in advanced HER2+ malignancies, ACTR707 was engineered to potentially avoid the on-target, off-tumor toxicity that has hindered the development of traditional CAR T cells for solid tumor cancers," said Jessica Sachs, M.D., Chief Medical Officer of Unum Therapeutics. "We are excited to continue this dose-escalation trial, having passed the DLT safety thresholds in this first, low-dose Cohort and we look forward to reporting additional data from multiple dose cohorts during 2020."
Additional details about the ATTCK-34-01 Phase 1 trial can be found here.
About ACTR707 and the ATTCK-34-01 Phase 1 trial for HER2+ solid tumor cancers
ACTR707 is derived from Unum’s novel proprietary Antibody-Coupled T cell Receptor (ACTR) platform. ACTR is designed to develop autologous engineered T-cell therapies that combine the cell-killing ability of T cells and the tumor-targeting ability of co-administered antibodies to exert potent antitumor immune responses. ACTR707 was engineered for properties that potentially optimize its function in solid tumors including increased proliferation, cytokine secretion, and persistence. Preclinical data demonstrate that, unlike traditional trastuzumab-based CAR-T cells that target HER2, ACTR707+ T cells administered with trastuzumab are highly selective for HER2-overexpressing tumor cells and discriminate against cells from normal tissues that express low levels of HER2. In addition, the preclinical activity of ACTR707+ T cells has been shown to be dose-dependent demonstrating control of ACTR707 activity by modulation of trastuzumab concentration.
While some patients with metastatic breast cancer and gastric cancer receive durable benefit from approved HER2-targeted therapies, many are refractory to or relapse from treatment. Additionally, there are other solid tumors that overexpress HER2 for whom existing HER2-targeted therapies are not approved. ACTR707 used in combination with trastuzumab is being developed in this trial to potentially serve patients whose treatment needs are not met by available HER2-targeted therapies.