MT-601 demonstrates favorable safety and durable responses in relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL)

Abstract Background: Significant treatment advances, including anti-CD19 CAR-T cells and bispecific antibodies (BsAbs), have improved outcomes among patients (pts) with relapsed/refractory (r/r) NHL. Despite these advances, many pts do not achieve durable responses after 2nd and 3rd line treatments, generating a large unmet medical need. Preliminary evidence from our Phase 1 trial demonstrated an excellent safety profile and durable anti-tumor responses in pts with r/r lymphoma that were treated with Multi-Antigen Recognizing (MAR) T cells targeting 5 antigens (PRAME, NY-ESO-1, survivin, MAGE-A4, SSX2) (Vasileiou et al. J Clin Oncol 2021). Updated survival analysis showed sustained complete responses (CRs) ≥4 years in 83% of r/r CAR-T naïve lymphoma pts that achieved initial CR (NHL n=3/4; and Hodgkin lymphoma, HL n=2/2) supporting MAR-T cell therapy as a novel treatment option in r/r NHL. With the objective of improving these promising clinical results, we have i) enhanced and simplified the manufacturing process resulting in a 4x improved product potency, ii) increased the targeted antigen profile from 5 to 6 by adding WT-1, and iii) tested the efficacy and safety of increasing cell doses (from 10x106 in the original study) up to 400x106. Here we present the dose escalation (DEsc), safety, and preliminary efficacy data from the Phase 1, multicenter, open-label APOLLO study (NCT05798897, sponsored by Marker Therapeutics) utilizing our novel MAR-T product (MT-601) in pts with r/r NHL. Methods: The APOLLO study is a Phase 1, multicenter, open-label study designed to evaluate the safety and efficacy of MT-601 in pts with HL or NHL who either relapsed or had incomplete response after CD19 CAR-T cells or were ineligible for CAR-Ts. Thirty-three pts were enrolled across 9 US clinical sites; 24/33 pts received treatment (NHL n=15; HL n=9), five pts have not received treatment due to: withdrawal (n=1), CR post-bridging (n=1), manufacturing failure (n=3); 4 are pending treatment (3 with product, 1 pending manufacture). Pts received MT-601 at dose levels ranging from 100x106 to 400x106 cells. The initial dosing schedule allowed up to 3 doses of 200x106 cells given every 2 weeks without lymphodepletion (LD) (n=5). Subsequent pts received standard doses of a LD regimen (Flu/Cy or bendamustine was allowed per protocol) and a single infusion of MT-601. The DEsc part of the study was initiated to evaluate increasing cell doses in a standard 3+3 design with safety, tolerability, and identification of the optimal dose for the dose expansion (DExp) phase as the primary endpoints. Results: The 15 r/r NHL pts (female n=5; male n=10) had a median age of 70 (range 38-82) and had undergone a median of 5 prior lines of therapy, including CAR-Ts (n=11) and BsAbs (n=5); dual exposed (n=4). All r/r NHL pts showed a favorable safety profile with no observed DLTs or ICANS and only 1 reported Grade 1 CRS (fever; no treatment was required), with no change in DLTs or ICANS between pts treated with and without LD. No DLTs were seen in the DEsc phase and the pre-specified maximum dose of 400x106 cells was selected for the ongoing DExp. Of the 15 treated r/r NHL pts (LBCL n=8, tFL/LBCL n=2, MZL n=2, FL n=2, MCL n=1), 12 were evaluable for response at the time of data cutoff, and 3 pts (LBCL n=1, MZL n=1, FL n=1) completed the DLT window with first disease assessment still pending. Evaluable pts had an objective response rate (ORR) of 66% (n=8/12) and a complete response rate (CRR) of 50% (n=6/12). Durable responses were observed (range 3-24 months) with 5 pts still responding ≥6 months, including 3 ≥12 months. Conclusion:Preliminary safety and efficacy data from the APOLLO study demonstrates a favorable safety profile and durable objective responses in r/r NHL pts treated with MT-601. Unlike genetically modified cell therapies, our approach uses endogenous T cells and appears to have low rates of Grade 1 CRS (6%) and no ICANS noted thus far. The favorable safety profile may allow for inclusion of heavily pre-treated pts not normally considered for more toxic cell therapies and safe outpatient administration of MT-601. No DLTs occurred at any dose level tested and the study has moved to DExp at the maximum cell dose (400x106 cells). Given the promising preliminary efficacy, DExp is focused on pts with CAR-T relapsed or ineligible DLBCL. The ongoing DExp will collect additional safety and durability data to confirm the initial promising clinical benefits.