On December 9, 2019 Molecular Templates, Inc., (Nasdaq: MTEM) a clinical-stage biopharmaceutical company focused on the discovery and development of the Company’s proprietary engineered toxin bodies (ETBs), which are differentiated, targeted, biologic therapeutics, reported the presentations of two posters on its pipeline programs at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2019 Annual Meeting, taking place December 7-10, 2019 in Orlando, Florida (Press release, Molecular Templates, DEC 9, 2019, View Source [SID1234552122]). One of these posters includes final results from the Phase 1/1b study of MT-3724, in subjects with relapsed/refractory (R/R) diffuse large b-cell lymphoma (DLBCL).
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Poster Title: Monotherapy Activity with the First CD20-Targeted Immunotoxin, MT-3724, in Subjects with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
Abstract Number: 4098
Presenter: Daniel Persky MD, University of Arizona Cancer Center
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials
Time: Monday, December 9, 2019: 6:00 PM-8:00 PM ET
This is a multi-center, open-label, dose-escalation and dose-expansion study of MT-3724, the first CD20 targeted immunotoxin to enter clinical trials. The Phase 1/1b portion of the study consists of two Parts in which a total of 27 subjects with NHL were enrolled; 21 in Part 1 (dose escalation) and 6 in Part 2 (expansion cohort), both closed to enrollment. In total, 25 subjects were evaluable for efficacy, including 19 subjects with DLBCL or mixed DLBCL/follicular lymphoma.
MT-3724 competes for binding with rituximab (RTX) and other commercially available CD20-targeting monoclonal antibodies. Consistent with this competition, initial efficacy data from the dose expansion study revealed only one of eight subjects with measurable serum rituximab (RTX) levels had any suggestion of benefit (a mixed response) to MT-3724.
The expansion cohort mandated negative serum RTX levels for enrolled subjects. Of the 13 serum rituximab negative (RTX-neg) DLBCL or mixed DLBCL/FL subjects, 5 responded (38% objective response rate) across the range of 5 to 100 μg/kg doses. Of the 5 responses, 2 were complete responses (CRs) and 3 were partial responses (PRs). Three patients had stable disease (including 2 patients with 49% and 47% tumor reductions) and 5 patients had progressive disease.
Of the 5 serum RTX-neg subjects with DLBCL who received MT-3724 at 50 μg/kg, the maximum tolerated dose (MTD), 3 responded (2 CR, 1 PRs). Of all 25 subjects evaluable for efficacy, 13 developed anti-drug antibodies (ADAs) or neutralizing antibodies (NAbs); the development of ADAs or NAbs did not preclude benefit of MT-3724, consistent with what has been seen with other immunotoxins. Safety events were mostly mild to moderate, and dose limiting toxicities (DLTs) were indicative of innate immune response, including grade 2 capillary leak syndrome and grades 1-3 arthralgias and myalgias. No life-threatening toxicities were attributed to MT-3724.
A Phase 2 dose-expansion portion of the study (Part 3) has been initiated to investigate MT-3724 in serum RTX-neg subjects with DLBCL. This is actively enrolling globally. A tolerable dose and schedule for the Phase 2 has been identified: 50 μg/kg/dose with a cap of 6000 μg/dose infused over 1 hour on Days 1, 3, 5, 8, 10 and 12 of a 21-day cycle. (ClinicalTrials.gov Identifier: NCT02361346).
Poster Title: A Phase 2a Open-Label Study to Investigate Safety and Tolerability (including the MTD), Efficacy, Pharmacokinetics, Pharmacodynamics and Immunogenicity of MT-3724 in Combination with Lenalidomide in Subjects with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Presenter: Jason Tache, DO, BRCR Medical Center
Abstract #: 1597
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials
Time and Location: Saturday, December 7, 2019: 5:30 PM-7:30 PM ET
MT-3724. a novel Engineered Toxin Body (ETB), possesses specific and high affinity for CD20+ cells and causes apoptosis via a unique mechanism of action, forced internalization of the ETB bound to the receptor, retrograde transport through the cytosol, and enzymatic deactivation of ribosomal function. Therefore, combining MT‑3724 with standard cytotoxic chemotherapy and/or immune modulatory agents may provide enhanced benefit in NHL treatment algorithms. This is a multi-center, open-label, multiple-dose Phase 2a study designed to evaluate MT-3724 in combination with lenalidomide in adult subjects with histologically confirmed, relapsed or refractory NHL. The primary objective is to determine safety and tolerability, including the MTD, of MT-3724 + lenalidomide. Secondary objectives include pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity and tumor response.
The study will be conducted in two parts: Part 1 will include MT-3724 dose escalation according to the modified 3+3 design to identify the MTD of MT-3724 in combination with standard doses of lenalidomide and will include up to 24 subjects with histologically confirmed NHL. Part 2 is designed to confirm the safety and tolerability of MT-3724 + lenalidomide in the MTD Expansion Cohort, where the dose declared as MTD of MT-3724 in Part 1 would be given in combination with lenalidomide in up to 40 subjects with CD20+ DLBCL. In addition, the PK, PD, immunogenicity and tumor response of MT-3724 + lenalidomide will be evaluated in Part 2.
The study is currently ongoing; eligible subjects will be identified and treated through competitive enrollment at multiple study centers (ClinicalTrials.gov Identifier: NCT03645395).
Copies of the posters presented at ASH (Free ASH Whitepaper) can be found in the Presentations section of Molecular Templates’ website at View Source