Trial testing T-cell therapy CER-1236 to now enroll myelofibrosis patients
No signs of dose-limiting toxicity seen to date in treating people with AML
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A clinical trial testing T-cell therapy CER-1236 is expanding to include people with hard-to-treat myelofibrosis. (Photo from iStock)
Cero Therapeutics is expanding enrollment in an early clinical trial that’s testing its T-cell-based therapy candidate CER-1236, to now include people with hard-to-treat myelofibrosis.
The Phase 1/1b CERTAIN-T study (NCT06834282) is a first-in-human, open-label trial — meaning both participants and investigators know the treatment being given to patients — initially designed for adults with acute myeloid leukemia (AML), a type of blood cancer. The therapy aims to use a patient’s own immune T-cells to target cancer cells.
This announcement follows positive safety data from the second group of trial participants with AML. The group completed dosing with no signs of dose-limiting toxicity 28 days after treatment, according to a company press release detailing the trial’s findings to date.
Those results support continued dose escalation in accordance with the study’s protocol, as well as the inclusion of people with both myelofibrosis and myelodysplastic syndrome (MDS), another type of blood cancer, per the company. Enrollment is underway at sites across the U.S. The developer did not state how many new patients would be enrolled.
“We are encouraged by the continued progress of the CERTAIN-T study, including completion of the second dose cohort and advancement to the next planned dose level,” said Robert Sikorski, MD, PhD, Cero’s chief medical officer. “The planned inclusion of patients with MDS and [myelofibrosis] reflects our interest in exploring CER-1236 across additional [blood-related] malignancies with significant unmet need.”
In myelofibrosis, bone marrow — the soft, spongy tissue found inside the hollow centers of most bones — produces too many abnormal cells, which, over time, drive inflammation and scarring, or fibrosis. That, in turn, disrupts the production of healthy blood cells in the body, leading to the disease’s symptoms. Common signs include an enlarged spleen and anemia, characterized by low red blood cell counts, often leading to fatigue and weakness.
CER-1236 uses patients’ own immune T-cells
Built on Cero’s proprietary platform, CER-1236 is a cell therapy made by using a patient’s own immune T-cells. In the lab, these T-cells are engineered to find and destroy cancer cells, and then infused back into the patient.
Currently approved cell therapies, known as CAR-T cells, work by recognizing a target on a cancer cell and signaling the immune system to destroy it. CER-1236 is designed to go a step further by also enabling T-cells to physically engulf and destroy cancer cells. Cero refers to these as chimeric engulfment receptor T-cells, or CER-T cells.
CERTAIN-T first tested the experimental therapy in adults with AML with relapsed or refractory (treatment-resistant) disease, those in remission with measurable residual disease, or newly diagnosed patients with TP53-mutated MDS/AML or AML.
The study is divided into two parts. Part 1 is an escalation phase that will assess the safety of different doses of CER-1236. This part will determine the best dose for Part 2, an expansion phase that will evaluate the safety and efficacy of CER-1236.
Cero has now treated a total of six patients in the trial. In the second group, three patients each received CER-1236 as a split dose on days zero and two. All three completed the required 28-day observation window to assess dose-limiting toxicities, meaning side effects severe enough to prevent further dose increases. Consistent with the results from the first three patients, no such toxicities were observed in any of these participants.
In addition, no patients experienced cytokine release syndrome, an immune overreaction that can cause fever and organ stress, or immune effector cell-associated neurotoxicity syndrome, which is a neurological side effect sometimes seen with cell therapies. There also were no treatment-related severe adverse events, according to Cero.
The company also reported observing an expansion of infused CER-1236 cells in patients after administration, indicating the cells multiplied in the body.
New group will receive T-cell therapy at higher dose
The trial is now moving to the third planned group to include transfusion-dependent MDS, high-risk MDS, and myelofibrosis patients who have previously received JAK inhibitor therapy. Such treatments have been shown to ease symptoms, but generally have limited effects on disease progression.
This group will receive CER-1236 at a higher split dose, the developer noted.
“The advancement of CER-1236 through dose escalation continues at a steady pace and we remain focused on evaluating its potential across hematologic malignancies with significant unmet need,” said Chris Ehrlich, CEO of Cero. “We look forward to providing additional clinical updates as the study progresses.”
Sikorski noted that Cero is moving ahead with care.
“As we proceed in accordance with the clinical protocol, our priority remains the careful evaluation of the safety, tolerability, pharmacokinetic profile, and preliminary clinical activity of CER-1236.”
