Triphase Accelerator and Catalent announced interim results for Triphase Accelerator's multi-center, open-label, monotherapy study of TRPH-222 in heavily pre-treated patients with relapsed and/or refractory B-cell lymphoma. The primary aim of the study is to determine the maximum tolerated dose of TRPH-222, with secondary aims of assessing safety, anti-tumor activity, and pharmacokinetics of the drug.
In the ongoing two-stage study, TRPH-222 is administered once every three weeks. To date, results in 19 heavily pre-treated patients with non-Hodgkin’s lymphoma have been evaluated, with five confirmed to have had a complete response at TRPH-222 doses of 0.6 to 5.6 mg/kg. Tumor reductions have been observed in patients with both indolent and aggressive disease, and durable responses to date have been observed in follicular, diffuse large cell, and mantle cell lymphoma patients. The trial is currently ongoing with a 10 mg/kg dose cohort.
Throughout the trial, which began in February 2019, TRPH-222 has been well-tolerated, with an overall benign safety profile. Notably, no peripheral neuropathies, which are typically observed with ADCs containing microtubule-interfering payloads, were observed in the patients to date. Similarly, elevations in liver enzymes and alterations in blood cell parameters, also commonly observed with ADCs, have been infrequent and mild and have reversed in all patients.
“The feedback from our investigators regarding the overall safety profile of TRPH-222 is very encouraging,” said Nancy Levin, Ph.D., Vice President of Development, Triphase Accelerator and TRPH-222 program lead. “We find that the current and emerging clinical data provide additional support for our preclinical observations of an excellent safety profile for this molecule,” she added.
"These interim results indicate that TRPH-222 is a very well-tolerated novel antibody-drug conjugate in this clinical study. The unique molecular design allows a higher delivery of the cytotoxic agent in the tumor bed, and, at the current doses tested, side effects have been mild and manageable. Of interest, clinical activity has been observed even at the lowest dose tested, and five complete remissions have been achieved in previously treated lymphoma patients. Together, our preliminary findings support our hypothesis that TRPH-222 is an active and safe novel targeted agent in B-cell malignancies," Dr. Hernandez-Ilizaliturri, MD, Chief of the Lymphoma Section at Roswell Park, and lead investigator for the TRPH-222-100 study, said.
TRPH-222 was originally developed by Catalent’s subsidiary Redwood Bioscience, Inc. using its proprietary SMARTag® platform, which provides optimized site-specific protein-modification and linker technologies.