CERo Therapeutics has reported early clinical findings from its ongoing Phase 1 CertainT-1 trial evaluating CER-1236 in patients with acute myeloid leukemia, highlighting initial safety observations and a platelet transfusion-free interval in a patient with myelodysplastic syndrome that progressed to AML.

The clinical update follows completion of the dose-limiting toxicity observation period for the first cohort in the study. According to the company, investigators observed expansion of CER-1236 cells with no cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome or treatment-related adverse events reported to date. Cell expansion was observed both with and without lymphodepletion.

The CertainT-1 trial is a first-in-human, multi-centre, open label Phase 1/1b study designed to assess the safety and preliminary efficacy of CER-1236 in patients with AML. The study includes patients with relapsed or refractory disease, those in remission with measurable residual disease, and newly diagnosed patients with TP53-mutated MDS or AML.

CERo also reported details from the second patient enrolled in the trial, who had MDS that progressed to AML with an inv3 chromosome translocation. Investigators administered four rounds of CER-1236 cells and observed a 61-day platelet transfusion-free interval following treatment. The company noted this exceeded a commonly referenced eight-week benchmark cited in clinical studies evaluating platelet transfusion independence. Transfusion independence ended after the patient subsequently received lymphodepleting chemotherapy followed by an additional round of CER-1236.

Robert Sikorski said: “The patient’s clinical course, including a platelet transfusion–free interval despite having advanced MDS/AML, is encouraging and supports continued evaluation of CER-1236 in diseases of the bone marrow.”

Based on the early findings, CERo has filed an amendment to the CertainT-1 protocol with the FDA to expand the trial to include additional cohorts of patients with advanced MDS and myelofibrosis. The company said the amendment reflects growing interest in evaluating CER-1236 across a broader set of bone marrow disorders.

Sikorski added: “We have amended the CertainT-1 trial to expand the focus to include MDS and MF patients going forward.”

The two-part study began with a dose escalation phase intended to determine the highest tolerated dose and the recommended dose for Phase 2. This will be followed by an expansion phase designed to further evaluate safety and efficacy. Primary outcome measures include the incidence of adverse events and serious adverse events, the incidence of dose-limiting toxicities, and estimates of overall response rate, complete response, composite complete response and measurable residual disease. Secondary outcome measures include pharmacokinetics.

CERo chief executive Chris Ehrlich said the protocol expansion represents an important milestone as the trial continues to progress through dose escalation.

“The evolution of this trial to MDS and MF is an important milestone as we continue to dose escalate, both in terms of volume and frequency,” Ehrlich said. “We remain focused on the careful and deliberate conduct of the dose-escalation phase and the systematic collection of safety data as the trial proceeds.”

CERo said it will host an analyst and investor conference call to discuss progress to date and plans for further development of CER-1236. The company is advancing the therapy as part of its broader effort to develop engineered T cell approaches that integrate elements of both innate and adaptive immunity for the treatment of cancer.