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

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 2^nd and 3^rd 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.