Experimental Lymphoma Drug Shows ‘Robust Clinical Activity,’ Researchers Say

An early-phase clinical trial showed encouraging results for patients with pretreated relapsed/refractory B-cell non-Hodgkin lymphoma who were given an experimental new drug, TRPH-222.

As of Jan. 7, 2022, the phase 1 trial — which is the first time the drug is being tested in humans — included 32 patients with relapsed/refractory non-Hodgkin lymphoma, with subtypes of the disease varying across the study population: 15 patients had indolent lymphomas (including 14 follicular lymphoma and one marginal zone lymphoma), while 15 had diffuse large B-cell lymphoma (DLBCL), one had follicular lymphoma and one had mantle cell lymphoma. On average, study participants underwent four prior lines of therapy.

Findings were most promising for those with relapsed/refractory follicular lymphoma. Thirteen patients with follicular lymphoma responded to the drug — meaning that their cancer shrunk as a result of treatment — including five patients who experienced a complete response, where there was no detectable trace of cancer. Disease responses tended to happen soon after receiving treatment and lasted when treatment ended, with an average duration of response of 24.9 months.

Additionally, one patient with DLBCL and one patient with mantle cell lymphoma experienced a complete response, too.

“TRPH-222 is a novel CD22-targeting antibody drug conjugate with a unique efficacy and safety profile that has successfully passed the phase 1 test. It demonstrated robust clinical activity in NHL, with durable complete responses that were enriched in (follicular lymphoma) patients,” stated Dr. Hernandez-Ilizaliturri, chief of the Lymphoma Section at Roswell Park Comprehensive Cancer Center in Buffalo, New York, and lead investigator for the TRPH-222-100 study, in a statement.

TRPH-222 is an antibody drug conjugate (ADC), which is a type of drug that binds to certain markers on cancer cells and attacks the disease, leaving health cells mostly unharmed. The side effects for the novel agent aligned with side effects that are well-known for ADCs: thrombocytopenia (low blood platelet count), neutropenia (low number of white blood cells called neutrophils) and impacted liver function. Overall, TRPH-222’s side effects were typically not severe and easy to manage.

“I particularly liked that my patients who achieved remissions with TRPH-222 were able to discontinue study drug and remain in remission for extended periods of time. The durable complete responses and minimal toxicity profile associated with TRPH-222 highlight its potential to be widely integrated into current treatment regimens,” Hernandez-Ilizaliturri said.

The positive findings from this small, early-phase trial warrant more research into TRPH, especially concerning how it can fit into drugs and regimens that are already established for this patient population, explained Dr. John Kuruvilla, of the Division of Medical Oncology and Hematology at Princess Margaret Cancer Center in Toronto, and co-primary investigator on the trial.

“My experience with TRPH-222 is that it is a highly active drug, is well tolerated and has a good fit in (follicular lymphoma). It was straightforward to administer to patients, with little concern for adverse events and no need for continual close monitoring … An agent like TRPH-222 could easily be incorporated into CD19 CAR-T treatment algorithms,” Kuruvilla said.

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