MT-601, in contrast to CAR-T therapies, is not genetically engineered.
Marker Therapeutics’ MT-601, an investigational multi-tumor associated antigen (multiTAA)-specific T-cell product being evaluated for the treatment of relapsed or refractory (r/r) lymphoma in the phase 1 APOLLO clinical trial (NCT05798897), has produced a complete response (CR) in a patient whose disease previously relapsed after treatment with an antiCD19 chimeric antigen receptor T-cell (CAR-T) therapy.1
The patient, who has diffuse large B-cell lymphoma and had received 4 previous lines of therapy in total, was the first patient to be treated in APOLLO. Without undergoing lymphodepletion before treatment with MT-601, the patient received 2 doses of the T-cell therapy at 200 million cells each. The patient’s complete metabolic response, assessed via PET-CT scans, was achieved at 8 weeks following the second dose. In terms of safety, Marker reported that the cell therapy was well-tolerated in the patient and that no treatment-related adverse events higher than grade 1 occurred. The company noted that these safety findings are in line with expectations based on results seen with other multiTAA-specific T cell products.
“We are delighted to announce that the first study participant treated in the APOLLO trial achieved a CR after treatment with MT-601,” Monic Stuart, MD, the chief medical officer of Marker Therapeutics, said in a statement.1 “This is a significant initial step forward in our phase 1 clinical trial and highlights the potential benefit of MT-601 in patients who have relapsed after antiCD19 CAR T-cell therapy. The patient will remain under close observation as we continue to monitor long-term treatment effects and the durability of response.”
The multicenter, open-label APOLLO trial is currently recruiting patients aged 18 to 100 years with r/r nonHodgkin lymphoma. The study, which consists of a dose escalation and dose expansion portion, is estimated to enroll 37 participants in total. In addition to the 200 million cell dose, Marker is also planning to evaluate a 400 million cell dose in APOLLO. Locations in California, Colorado, Tennessee, and Texas are currently recruiting patients. The investigational new drug application for APOLLO was originally cleared by the FDA in August 2022.2 The trial is estimated to be completed in February 2028.
“The CR we have observed in this CAR T relapsed patient with lymphoma marks a remarkable milestone for Marker and our technology,” Juan F. Vera, MD, the president and chief executive officer of Marker Therapeutics, added to the statement.1 “Our APOLLO trial is an important area for MT-601 assessment, as up to 60% of patients treated with anti-CD19 CAR T therapies relapse within 1 year. While a complete response in our first patient treated with MT-601 is certainly encouraging, the focus of the APOLLO study is to continue to treat and evaluate additional participants in this phase 1 study.”
MT-601, in contrast to typical CAR-T therapies, is not genetically engineered. Instead, it consists of autologous tumor-specific T-cells that have been selectively expanded. Marker, which does not have any genetically modified cell products in its pipeline, believes that this approach will allow for simplified and cheaper manufacturing and a lower risk of toxicities, while still having potential for clinical benefit. MT-601 is directed at Survivin, PRAME, WT-1, NY-ESO-1, SSX-2, and MAGEA-4, 6 tumor antigens that are upregulated in lymphoma cells.
Marker Therapeutics is also developing MT-401 (zelenoleucel), an investigational allogeneic MultiTAA T-cell therapy intended for the treatment of post-transplant acute myeloid leukemia (AML).3 MT-401 is currently being evaluated in the phase 2 ARTEMIS clinical trial (NCT04511130). Notably, in September 2022, Marker received a $2 million grant from the FDA for the purpose of advancing ARTEMIS, specifically with the intent of helping to support the trial’s treatment arm for patients with posttransplant AML with minimal residual disease.