On June 15, 2020 Cue Biopharma, Inc. (NASDAQ: CUE), a clinical-stage biopharmaceutical company engineering a novel class of injectable biologics designed to selectively engage and modulate targeted T cells within the body, reported an update on its Phase 1 trial of CUE-101 monotherapy as second-line or later therapy for patients with HPV+ recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) (Press release, Cue Biopharma, JUN 15, 2020, View Source [SID1234608302]).
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As of June 15, 2020, the ongoing Phase 1, first-in-human, multicenter trial has enrolled 13 patients, with a majority of patients having received multiple cycles of therapy. In cohorts 1 through 4, patients received dosages of 0.06 mg/kg, 0.18 mg/kg, 0.54 mg/kg and 1.0 mg/kg, respectively. Out of the 13 patients enrolled, there are six patients presently remaining on study for ongoing data generation.
As recently presented by Daniel Passeri, chief executive officer of Cue Biopharma, at the Jefferies Healthcare Conference on June 4, preliminary observations include:
Pharmacokinetic data indicating drug exposure that is in line with preclinical projections and is dose-proportional; furthermore, comparable exposures have been observed upon repeated administration
Pharmacodynamic data indicating selective expansion of the targeted T cells in the peripheral blood of several patients across cohorts 2 and 3; evaluation of activity in patients from cohort 4 is ongoing
Preliminary radiographic evidence indicating CUE-101 is clinically active, with a patient from cohort 2 experiencing reduction of target lesion following two cycles of CUE-101 that was sustained through day 84 of treatment, at which point the patient was confirmed as having stable disease; this patient continues to be on study
To date, CUE-101 has been overall well-tolerated with treatment-related adverse events (AEs) primarily being mild-to-moderate (Grade 1 or 2) with no discontinuations due to AEs. One patient from dose cohort 4 at 1.0 mg/kg experienced a Grade 3 adverse event (anemia and fatigue) that was reported on day 19 of the 21-day safety evaluation period. Of note, this patient had an underlying condition, and following a blood transfusion the anemia resolved, allowing for the patient to receive the second planned dose of CUE-101 at the same 1.0 mg/kg dose on June 8 which to date, appears to have been well tolerated. This patient remains on study. On June 5, the Safety Review Committee designated this event as a possible drug-related dose limiting toxicity (DLT), and thus an additional three patients will be enrolled at the 1.0 mg/kg dose level within cohort 4 per protocol. This will allow for a more thorough evaluation of CUE-101 pharmacodynamics and clinical activity in order to better define the therapeutic window. The fourth patient in cohort 4 has received their cycle 1 dose and the other two patients have been identified and are scheduled to receive their first dose of CUE-101 before the end of this month. If no additional DLTs emerge within these three additional patients, the company will proceed to the cohort 5 dose.
"Based on the preliminary safety, tolerability, biomarker metrics and clinical activity observed to date, we are highly encouraged that CUE-101 appears to have an attractive therapeutic window. We are looking forward to launching our combination trial with Merck’s Keytruda (pembrolizumab) as well as a neo-adjuvant trial later this year to generate clinical data sets pertaining to tumor-infiltrating lymphocytes, or TILs, from the targeted T cell population," said Ken Pienta, M.D., acting chief medical officer. "Moreover, based on our collective data to date, we are now well-positioned to further exploit the flexibility of our trial design which allows us to expand any given dose level up to nine patients, further enhancing the supporting data evaluating the drug’s safety and therapeutic window. This will enable us to select the optimal dose to be advanced into Part B of the Phase 1 trial."
About the CUE-100 Series
The CUE-100 series consists of Fc-fusion biologics that incorporate peptide-MHC (pMHC) molecules along with rationally engineered IL-2 molecules. This singular biologic is anticipated to selectively target, activate and expand a robust repertoire of tumor-specific T cells directly in the patient. The binding affinity of IL-2 for its receptor has been deliberately attenuated to achieve preferential selective activation of tumor-specific effector T cells while reducing potential for effects on regulatory T cells (Tregs) or broad systemic activation, potentially mitigating the dose-limiting toxicities associated with current IL-2-based therapies.