- Researchers evaluated the safety of novel antibody-drug conjugate
- No serious adverse events observed with TRPH-222 single-agent therapy
- Further studies of TRPH-222 are warranted for B-cell lymphoma patients
TRPH-222-100 was a phase 1 open-label, multicenter, dose-escalation study that sought to determine the safety, tolerability, and pharmacokinetics of TRPH-222 monotherapy in patients with relapsed/refractory non-Hodgkin lymphoma. TRPH-222 is a novel antibody drug conjugate targeting CD22 — a receptor found in malignant B-cell lymphoma.
“TRPH-222 is generated using a novel technology that produces a very specific and stable bond between the antibody and the anticancer chemotherapy drug. The antibody binds to the cancer cells and delivers the chemotherapy agent inside the lymphoma cells,” explains Dr. Hernandez-Ilizaliturri, who is Chief of Lymphoma, Professor of Medicine and Associate Professor of Immunology at Roswell Park. “Because of the novel engineering technology used to make TRPH-222, there is very small amount of free drug in the patients and, therefore, we expected that it could be given safely and with fewer side effects than other drug conjugates previously approved by the FDA to treat cancer.”
The study included a dose-escalation stage followed by a dose-expansion stage. TRPH-222 was administered intravenously once every three weeks to the study population, which included patients with diffuse large B-cell lymphoma, follicular lymphoma, mantel cell lymphoma and marginal-zone lymphoma. Single-patient cohorts received doses of TRPH-222 beginning at 0.6 mg/kg until the occurrence of a dose-limiting toxicity or a nonhematologic adverse event (grade 2 or higher). The protocol then converted to a 3+3 design, where patients were added to the study in groups of three.
As of June 30, 2020, 22 patients were enrolled in the study. Two dose-limiting toxicities have occurred. Other treatment-related adverse events of grade 3 or higher included thrombocytopenia, neutropenia, hypertension and dry eyes. The researchers observed no treatment-related grade 5 toxicities or serious adverse events. Ten patients experienced grade 1 or 2 ocular events, which resolved to grade 1 or less with dose interruptions and reductions as well as lubricant eye drops.
The pharmacokinetic profile of TRPH-222 showed a long serum half-life. To date, no anti-drug antibodies have been found in analyzed samples, and peripheral B-cells were reduced at all TRPH-222 dose levels.
Eleven patients remain enrolled in the trial. Reasons for study discontinuation were progressive disease and investigator decision. At the end of cycle 6, the researchers reported five complete responses and one partial response. Four patients with complete responses at the end of cycle 9 are now off treatment, with ongoing follow-up for safety and durability of response.
“TRPH-222-100 is the first clinical trial to evaluate the safety and efficacy of TRPH-222 as a single agent in patients with relapsed/refractory B-cell lymphoma,” says Dr. Hernandez-Ilizaliturri. “Our data demonstrated that TRPH-222 was well-tolerated at the dose levels tested and very effective at disease control among patients with different subtypes of B-cell lymphoma.”
These findings support additional clinical trials of TRPH-222 alone and in combination with other agents for this patient population, he notes.
ASH 2020 Presentation Details A Phase I Pharmacokinetic (PK) and Safety Study of Trph-222 in Patients with Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (R/R NHL): Dose-Escalation Results Abstract 701 Presenting author: Francisco J. Hernandez-Ilizaliturri, MD, Roswell Park Comprehensive Cancer Center Time/date: Monday, Dec. 7, 1:45 p.m. PST Session: 623, Mantle Cell and Indolent B-Cell Lymphoma – CAR-T and immunotherapy clinical studies Hematology Disease Topics & Pathways: antibodies, Biological, Follicular Lymphoma, Diseases, Marginal Zone Lymphoma, Therapies, Mantle Cell Lymphoma, Non-Hodgkin Lymphoma, B-Cell Lymphoma, DLBCL, Lymphoid Malignancies
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