An investigational new drug application has been accepted by the FDA allowing for the start of a phase 1 trial to evaluate the tolerability of CNTY-101 in patients with relapsed or refractory CD19 positive B-cell malignancies
The FDA has cleared an investigational new drug application (IND) for CNTY-101 in patients with relapsed or refractory CD19 positive B-cell malignancies, according to Century Therapeutics, Inc.1
CNTY-101 is the first allogeneic cell product candidate to be engineered with 6 precision gene edits including a CD19-CAR, Allo-Evasion™ technology, IL-15 cytokine support and a safety switch. The cell therapy is made from a clonal iPSC master cell bank that yields a homogeneous product where the infused cells have the intended modifications.
Now, the phase 1 ELiPSE-1 trial (NCT05336409) to evaluate CNTY-101 in patients with relapsed or refractory CD19 positive B-cell malignancies is expected to begin this year.
“This IND clearance is a significant milestone for Century as we execute on our vision to merge two disruptive platforms, precision gene editing and the powerful potential of iPSCs, to potentially move the allogeneic cell therapy field forward, and continue on our path to becoming a leader in the space,” said Lalo Flores, chief executive officer of Century Therapeutics, in a press release. “We believe that CNTY-101, our first and wholly owned product candidate, will be the most technically advanced and differentiated CD19-targeted cell product when it enters the clinic, which is anticipated to occur later this year. We look forward to assessing the potential of Allo-Evasion™ to prevent immunological rejection and enhance persistence of multiple dosing of CNTY-101 regimens with the aim to increase the proportion of patients that achieve durable responses.”
The multi-center, dose-finding, open-label, phase 1 ELiPSE-1 trial aims to assess the safety, tolerability, pharmacokinetics and preliminary efficacy of CNTY-101 in patients with relapsed or refractory CD19-positive B-cell malignancies. In the trial, all patients will be administered an initial standard dose of conditioning chemotherapy, consisting of cyclophosphamide (300 mg/m2) and fludarabine (30mg/m2) for 3 days.2
Patients will be given either schedule A, including a single-dose escalation of CNTY-101 and subcutaneous IL-2, or schedule B, a 3-dose schedule per cycle of CNTY-101. If patients demonstrate a clinical benefit, they will be eligible for additional cycles of treatment with or without additional lymphodepletion.
Enrollment is open to patients aged 18 years and older with CD19-positive relapsed or refractory B-cell Non-Hodgkin's lymphoma. Patients are required to have received at least 2 or 3 lines of systemic therapy, previous therapy which included a CD20-targeted agent and an anthracycline or alkylator, measurable disease on screening evaluations, an ECOG performance status of 0 or 1, adequate organ function, and a life expectancy of greater than 12 weeks.
The primary end points of the study are maximum tolerated dose (MTD) as determined by the percentage of patients with dose limiting toxicities (DLTs) and DLTs based on severity and the recommended phase 2 regimen. Secondary end points include complete response rate, objective response rate, duration of response, time to treatment response, progression-free survival, overall survival, and safety.
“CNTY-101 is the first allogeneic cell product candidate with six genetic modifications incorporated using sequential rounds of CRISPR-mediated homologous recombination and repair that has received IND clearance by the FDA,” added Luis Borges, chief scientific officer of Century Therapeutics, in the press release. “We believe CNTY-101 will demonstrate the power of Century’s iPSC technology and cell engineering technology platforms. This accomplishment is a testament to the expertise and dedication of our team as we continue to make progress developing our pipeline of iPSC-derived NK and T cell product candidates.”