On June 6, 2022 Molecular Templates, Inc., (Nasdaq: MTEM, "Molecular Templates" or "MTEM") a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, engineered toxin bodies (ETBs), reported highlights from the two poster presentations on its clinical programs that were presented on June 5th at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, taking place June 3 through June 7, 2022 at the McCormick Place Convention Center in Chicago, IL (Press release, Molecular Templates, JUN 6, 2022, View Source [SID1234615641]). Copies of the posters presented at ASCO (Free ASCO Whitepaper) can be found in the "Investors" section of Molecular Templates’ corporate website under Presentations.
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"ETBs offer novel biology with the potential to drive unique clinical outcomes, even against well-explored targets," said Eric Poma, Ph.D., CEO and CSO of Molecular Templates. "We are seeing differentiated pharmacodynamic effects and signs of clinical benefit in patients in our on-going Phase I study with MT-6402, our PD-L1 targeting agent, from both that agent’s direct cell-kill effects and its antigen seeding ability. For MT-5111, our HER2-targeting agent, we have achieved exposures in dose-escalation with which have generated pharmacodynamic effects that may be associated with clinical benefit."
Poster Title: First-in-human, dose escalation and expansion study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing relapsed/refractory advanced solid tumors: Interim Data
Authors: Eugene Ahn, MD; Brian Van Tine, MD; John D. Powderly, MD; Herbert L. Duvivier, MD, JD; Drew Rasco, MD; Agnes Rethy, MD; Chris Moore, PhD; Amy Yuet, PhD; Rachael M. Orlandella, PhD; Swati Khanna, PhD; Joseph D. Dekker, PhD; Angela Georgy, PharmD; David R. Spigel, MD
Abstract #: 2521
Poster highlights:
Data were presented on 12 patients with PD-L1+ relapsed/refractory disease across two dose cohorts: 16 mcg/kg (n=6) and 24 mcg/kg (n=6). Treatment is on-going in the 32 mcg/kg cohort with no dose-limiting toxicities (DLTs) observed to date in the third cohort.
Pharmacodynamic (PD) effects including PD-L1+ dendritic cell and monocyte cell depletion and T cell activation have been observed in the majority of patients. The extent and timing of these PD effects appear dose-related with patients in the 24 mcg/kg cohort generally showing a more rapid and profound PD effect. Patients in both cohorts demonstrated increases in IL-2.
One patient in the first cohort with non-small cell lung cancer (NSCLC) (osseous non-measurable disease only) that had progressed after prior checkpoint therapy (PD-1 and CTLA-4) showed qualitative reduction in tumor burden.
One DLT was observed in a single patient (24 mcg/kg) who experienced dermatitis that resolved rapidly with systemic steroids. The patient was rechallenged without incident at 24 mcg/kg. No other DLTs have been reported.
Based on these findings, monotherapy will continue to be investigated and a combination approach with a PD-1 inhibitor is also being considered for select populations of patients.
Poster Title: A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results
Authors: Brian A. Van Tine, MD, PhD; Joleen M. Hubbard, MD; Monica M. Mita, MD; Minal A. Barve, MD; Erika P. Hamilton, MD; Frances Valdes, MD; Daniel Ahn, DO; Joshua Pelham; Admasu Mamuye, MD; Amy Yuet, PhD; Diana Yurewicz, MPH; Yanning Liu, PhD, Taunya Smith, MPH; Andrés Machado Sandri, MD; William J. Edenfield, MD; Aki Morikawa, MD, PhD; Meena Okera, MD; Zev A. Wainberg, MD
Abstract #: 2583
Poster highlights
Data were presented on 35 patients with HER2+ relapsed/refractory disease across eight dose cohorts ranging from 0.5 mcg/kg to 13 mcg/kg (N=31) and the breast cancer expansion cohort (N=4): Treatment is on-going with the 17 mcg/kg cohort having been closed and dosing has begun in the 23 mcg/kg cohort.
No Grade 4 or 5 treatment emergent adverse events or DLTs have been identified in 35 patients, including 2 patients who were treated for 6 months or longer.
Serum concentration of MT-5111 showed predictable and dose-proportional increasing exposure in the last three evaluable dose cohorts.
Higher MT-5111 doses (6.75 mcg/kg and above) appear to saturate circulating soluble HER2 (sHER2) receptors with patients’ HER2 levels stabilizing or decreasing at higher doses.