Copiktra May Be Treatment Option for Advanced Marginal Zone Lymphoma, Trial Data Show

Copiktra (duvelisib), developed by Verastem Oncology, may be an effective and reasonably safe treatment option for people with marginal zone lymphoma who failed to respond to prior therapies including rituximab, Phase 2 data show.

The findings were presented at the Lymphoma & Myeloma 2019 International Congress, held Oct. 23-26 in New York, in a poster titled “Characterisation of duvelisib in patients with refractory marginal zone lymphoma: data from the phase 2 DYNAMO trial.”

Copiktra is an orally available small molecule inhibitor that blocks the activity of two enzymes — PI3K-delta and PI3K-gamma — known to support the growth and survival of malignant B and T cells.

It is approved in the U.S. for chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma patients after at least two prior lines of therapy. Approval was supported by results from the DYNAMO Phase 2 study (NCT01882803) in indolent non-Hodgkin’s lymphoma, and the DUO Phase 3 clinical trial (NCT02004522) in CLL/SLL.

DYNAMO included patients with non-Hodgkin’s lymphoma — including follicular lymphoma, SLL, and marginal zone lymphoma. In the first two patient populations, it showed response rates of 42% and 68%, respectively.

Researchers now detailed data from 18 trial patients with marginal zone lymphoma, where response rates (39%). Although this response was not as strong as the rate seen in other lymphoma types, it was promising as treatment options are limited for this patient group.

These 18 DYNAMO patients had a median of two prior lines of therapy, ranging from one to eight. Their median age was 67, most (72%) were men, and 12 (67%) of the 18 were refractory (failed to respond) to two treatment regimens.

Copiktra was given in 25 mg doses twice daily, until disease progression or unacceptable toxicity. Patients received the therapy for a median of 8.4 months. All patients were also given preventive treatment against Pneumocystis jiroveci, a pneumonia-causing fungus often found in non-Hodgkin’s lymphoma patients treated with rituximab.

DYNAMO’s primary goal was to determine overall response rate, or the proportion of patients whose tumor load reduced with treatment, assessed by an independent review committee. Secondary goals included duration of response, the median time patients lived without cancer progression, overall survival, time to response, and side effects and other safety parameters.

In total, seven patients (39%) showed a reduction in tumor burden after Copiktra treatment, and one had a complete response (total tumor eradication). Responses were seen after a median of 3.7 months on treatment, and after a median follow-up of 31.2 months, more than half of these patients were still responding to Copiktra.

Patients showed no signs of disease progression for a median time of 15.5 months.

The most common severe (grade 3) adverse events were low levels of neutrophils (a kind of immune cell) and diarrhea. One third of the patients (33%) discontinued the treatment due to a side effect, including three who had a partial response — two of these patients had available follow-up imaging, and continued to show sustained responses more than one year after stopping Copiktra.

One patient died due to pancolitis (inflammation of the colon), deemed potentially related to Copiktra.

“These preliminary findings suggest that duvelisib represents a promising treatment option that warrants further investigation in patients with double-refractory MZL [marginal zone lymphoma] for whom limited treatment options exist,” the researchers concluded.