Safety and efficacy of MT-601 in relapsed or refractory (r/r) Hodgkin lymphoma

Abstract Background: Hodgkin lymphoma (HL) is a rare B-cell lymphoma with approximately 8,570 new cases diagnosed annually in the United States, representing ~10% of all lymphomas. The treatment options for patients (pts) with r/r HL include immune checkpoint inhibitors or brentuximab vedotin, an anti-CD30 antibody-drug conjugate. However, many pts do not achieve long-term durable remission even after undergoing consolidation with autologous hematopoietic stem cell transplant (HSCT). Therefore, novel treatments are urgently needed for pts with r/r HL. To address this unmet medical need, we investigated MT-601 as a novel treatment option in r/r HL pts. MT-601 is a non-genetically engineered, autologous, Multi-Antigen Recognizing (MAR) T cell product targeting 6 tumor-specific antigens (PRAME, NY-ESO-1, survivin, MAGE-A4, SSX2, WT1). Here we are reporting the preliminary safety and efficacy data from the Phase 1 APOLLO study (NCT05798897, sponsored by Marker Therapeutics) investigating MT-601 in pts with HL. Methods: The APOLLO study is an open-label, multicenter, Phase 1 clinical study designed to evaluate the safety and efficacy of MT-601 in r/r patients with Non-Hodgkin Lymphoma (NHL) or HL. The trial follows a 2-stage design: an initial 3+3 dose escalation followed by a dose expansion phase. Main eligibility criteria included ECOG 0-1, ≥2 prior therapies, measurable disease (per Lugano 2014), and adequate heme, liver, renal, and cardiac function. Key exclusion criteria included bulky disease (≥10 cm), primary immunodeficiency or severe autoimmune disorder. Thirty-three pts were enrolled across 9 US clinical sites, with 24 B-cell lymphoma pts treated with MT-601 (NHL n=15; HL n=9). Five patients were not treated due to withdrawal (n=1), complete response (CR) post-bridging (n=1), and manufacturing failure (n=3); 4 are pending treatment (3 with product, 1 pending manufacture). HL pts received standard doses of a lymphodepletion chemotherapy (LDC) regimen (Flu/Cy or bendamustine was allowed per protocol) for three consecutive days (Day -5 to Day -3) before infusion of MT-601 (MT-601 doses: 200 x106 cells n=3; 300 x106 cells n=2; 400 x106cells n=4). Initial disease assessment was conducted 8 weeks post MT-601 infusion. Results: The 9 HL pts (female n=4; male n=5) had a median age of 43 (range 30-75) and had undergone a median of 8 prior lines of therapy, with all 9 pts having received prior brentuximab, PD-1 and HSCT (autologous n=5; allogeneic n=2; autologous and allogeneic n=2). The dose escalation portion of the study was successfully cleared, with no observed dose limiting toxicities (DLTs) at the pre-specified maximum dose (400x106 cells). All 9 HL pts showed a favorable safety profile with no reported neurotoxicity/Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and only 1 reported Grade 1 Cytokine Release Syndrome (CRS) event (fever; no treatment required). No grade 3/4 non-hematological toxicities were observed and no deaths occurred in the initial 30 days post MT-601 infusion. With a median follow-up of 3 months (range 2-4), we observed an objective response rate (ORR) of 78% (n=7/9) with a CR rate of 11% (n=1/9). The pt with a CR received 6 prior lines of therapy and achieved a CR at first response assessment 8 weeks after treatment with MT-601 (200x106 cells). Of the 7 responders, 2 demonstrated a sustained partial response (PR) 4 months post MT-601 infusion. One of these patients subsequently received allogeneic HSCT and showed durable CR 3 months post-transplant. Three pts initially showed PR but later experienced disease progression. At the time of data cutoff, 3/7 responders showed continued response to MT-601. Conclusion: These preliminary findings from the Phase 1 APOLLO study demonstrate that MT-601 has a favorable safety profile and early objective responses in heavily pre-treated HL pts. The encouraging tolerability in a population with limited treatment options supports the potential of MT-601 to address a significant unmet medical need and warrants further clinical examination. We will continue to collect additional safety and durability data to confirm the initial promising clinical results.