Marker will initiate a company-sponsored study after an initial trial at Baylor College of Medicine showed positive safety data.
The FDA has cleared Marker Therapeutics’ investigational new drug application (IND) for MT-601, an investigative T-cell therapy for the treatment of relapsed/refractory non-Hodgkin lymphoma (NHL).
“This new clinical trial will build upon results that were observed in the phase 1/2 TACTAL study conducted by Baylor College of Medicine, which assessed the safety and efficacy of 5-antigen-directed multiTAA-specific T cell product,” Mythili Koneru, MD, PhD, chief medical officer, Marker Therapeutics, said in a statement. “In the TACTAL study, BCM observed long-term CR rates that were comparable to recently approved CD19 CAR-T therapies, even at very low cell doses. Unlike CD19 CAR-T cell therapies, patients receiving multiTAA-specific T cell product had superior durability of response, without the severe toxicities that commonly occur with other adoptive cell therapies, such as cytokine release syndrome or neurotoxicity. Based on these results, we believe that multiTAA-specific T cell products can be easily administered in an outpatient setting without hospitalization.”
Marker will be initiating a phase 1 trial evaluating MT-601 in patients for whom CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has failed or who are ineligible for CAR T-cell therapy. MT-601 is a multi-tumor-associated antigen (multiTAA)-specific T cell therapy that is targeting the antigens NY-ESO-1, MAGEA4, PRAME, Survivin, SSX, and WT-1.
“FDA clearance of our IND for MT-601 is a significant milestone as we advance our pipeline in a number of Company-sponsored trials,” Peter L. Hoang, president and chief executive officer, Marker, added to the statement. “We believe that MT-601, which targets six tumor-associated antigens highly expressed in lymphoma, has the potential to build upon results of the TACTAL study. We look forward to initiating our Company-sponsored Phase 1 study next year.”
MT-106 was evaluated in the previous TACTAL study (NCT01333046) conducted at Baylor College of Medicine. The therapy was evaluated against the same TAAS with the exception of WT-1. The therapy showed a tolerable safety profile in patients with NHL and the IND clearance included the addition of the WT-1 antigen for evaluation. The study will evaluate a dose level of 200 million cells per infusion of MT-601, an increase from the 10-40 million cell dose range used in the TACTAL study. Marker Therapeutics has developed and adapted a 9-day manufacturing process to support the dose increase.
“We believe that the most important finding of the TACTAL study was that the administration of multiTAA therapy consistently drove an enhanced immunological response from the patient’s own immune system, which we believe was due to the lack of lymphodepletion which allowed the patient’s own immune system to play a part,” Koneru added to the statement. “We believe that this phenomenon, known as epitope spreading, was critical in driving more durable responses than have been observed with other cell therapies like TCRs and CAR-Ts. It is notable that none of the patients who developed a CR in the TACTAL study relapsed during the follow up period, and several patients have been in CR for over five years at their last follow-up. This contrasts strongly with the experience of CD-19 CAR-Ts, where up to 40% of patients are expected to relapse within 12 months of developing a complete response.”