The dosing of the first patient took place in December 2022 and no adverse events related to the therapy have been reported.
The first patient has been dosed in a phase 1/2 clinical trial (NCT04959903) evaluating Smart Immune’s SMART101, an investigational allogeneic human T lymphoid progenitor (HTLP) cell therapy intended to assist in the restoration of the immune system of patients who have received T-cell-depleted allogeneic hematopoietic stem cell transplantation (HSCT).
SMART101 consists of T-cell progenitors which are derived from donor blood stem cells via the company’s ProTcell T-cell therapy platform in a 7-day process. The cells are intended to develop into functional and self-tolerant T-cells in the thymus of the patient after injection. Based on findings from preclinical research, Smart Immune expects that this process could allow for recovery of the patient’s immune system within 100 days, a substantial decrease from the typical 1 year to 18 months observed following allogeneic HSCT. The dosing of the first patient took place at Memorial Sloan Kettering Cancer Center (MSK) in December 2022. To date, no adverse events (AEs) related to the therapy have been reported.
“The infusion of the first patient is a significant milestone in our journey to address the challenge of slow immune reconstitution after allogeneic HSCT, using the power of the thymus,” Frédéric Lehmann, chief medical officer, Smart Immune, said in a statement regarding the news of the first patient’s dosing. “We are grateful to the dedicated investigators at MSK and look forward to continuing enrollment in this important trial.”
The multicenter, open-label clinical trial is expected to enroll approximately 36 patients adult or pediatric patients who have been affected by acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) according to study-specific criteria. The adult patient group will include patients aged 21 years or older who are eligible for allogeneic HSCT, have a Karnofsky Performance Status of at least 70%, and have normal organ function. The pediatric patient group will include patients under the age of 21 who are eligible for allogeneic HSCT, do not have a matched sibling donor, have a Karnofsky/Lansky Performance Status of at least 70%, and have normal organ function. Patients who have undergone prior therapy with allogeneic stem cell transplantation, those who are planning to receive an HLA matched cord blood transplantation (8/8 allele matched), and those who have been treated with another cell therapy within 1 month will be excluded.
The study’s primary end points include the cumulative incidence of grade 3 to 4 graft versus host disease, the occurrence of AEs related to SMART101, and CD4+ T-cell count, all of which will be assessed for the 100 day timeframe after patients receive HSCT. Secondary end points include the time for T-cell immune reconstitution, the cumulative incidence of infections, and non-relapse mortality. Overall survival and disease-free survival will also be assessed. The company has noted that SMART101 will be manufactured for the trial by the MEARY Center for Cell and Gene Therapy at Paris St Louis Hospital.
“We are excited to sponsor this pioneering trial,” Karine Rossignol, chief executive officer and co-founder, Smart Immune, added to the statement. “Accelerated reconstitution of a full polyclonal T-cell repertoire after stem cell transplantation could improve both quality of life and clinical outcomes for patients with acute leukemia, and we look forward to releasing more data as the trial progresses.”