For some 15 years, a combination of drugs referred to as ABVD has been the standard of care to treat Hodgkin lymphoma. But that may soon change based in part on trial data from Seagen and Takeda’s lymphoma drug Adcetris.
In the phase 3 Echelon-1 study in untreated patients with Stage III/IV Hodgkin lymphoma, a combination treatment including Adcetris outperformed (PDF) the standard of care combo in a secondary measure—overall survival.
In a six-year median follow-up, patients treated with Adcetris experienced a 41% reduction in the risk of death compared with standard of care. In a trial that included 1,334 patients, there were 39 deaths in the Adcetris arm versus 64 in the ABVD group. The safety profile of Adcetris was consistent with previous studies.
“Patients with advanced-stage Hodgkin lymphoma have not benefitted from an improvement in overall survival outcomes for far too long,” Chris Arendt, Ph.D., Head of Oncology Cell Therapy and Therapeutic Area Unit, Research and Development, at Takeda, said in a release. “These findings represent a transformative improvement in care.”
In the Adcetris combo, the Seagen and Takeda drug replaces the antibiotic chemotherapy bleomycin. The three other standard of care drugs—doxorubicin, vinblastine and dacarbazine—remain the same.
Adcetris won FDA approval for first-line Hodgkin lymphoma in 2018 after meeting the trial’s primary endpoint—progression-free survival. Now, Seagen is touting Adcetris’ ability to extend lives.
“These results clearly show that the addition of (Adcetris) to chemotherapy improves the long-term outcome of patients and the combination should be considered a standard of care,” Stephen Ansell, M.D., Ph.D., Mayo Clinic, and Echelon-1 study investigator, said in a statement.
Seagen and Takeda will present the findings—along with others on Adcetris—during the American Society of Clinical Oncology (ASCO) conference, next week in Chicago, and at the European Hematology Association (AHA) annual meeting in Vienna, Austria, on June 10.
While the companies already have won approval for Adcetris in first-line Hodgkin disease, with this and other new data, they are exploring further opportunities with the drug.
Also on the docket for Seagen at ASCO is an assessment of Adcetris’ performance in relapsed/refractory diffuse large B-cell lymphoma (DLBCL).
Patients with DLBCL who relapse after or are ineligible for hematopoietic stem cell transplant (HSCT) or chimeric antigen receptor T cell (CAR-T) therapy generally have poor outcomes. But new data may provide a rationale for combining Adcetris with Bristol Myers Squibb's Revlimid and Roche's Rituxan.
The triplet combo showed promise in a phase 1 trial, with 57% of participants showing tumor shrinkage. Patients survived a median 10.2 months without disease progression and experienced 14.3 months of overall survival.
Meanwhile, in the phase 3 Echelon-3 study—enrollment in which is underway—an open-label safety run-in was conducted prior to enrollment. The early findings suggest that the triplet is active in R/R DLBCL, evidenced by a 70% tumor objective response rate.
Of the 10 patients studied, four had a complete metabolic response. And of the six patients in the run-in who had received prior CAR-T treatment, four had a complete or partial response.
The run-in also revealed an acceptable safety profile. Four of the 10 patients discontinued treatment because of an adverse event, two of which were treatment related, including one case of Grade 2 fatigue and one case of Grade 3 anemia.
Treating DLBCL presents a lucrative opportunity. Roche’s Polivy, which has posted impressive results in a phase 3 trial in DLBCL is looking at peak sales of $2.4 billion, including $2.1 billion of which could come from a DLBCL indication, according to Jefferies analyst Peter Wellford.
Also poised for a windfall in DLCBL is Gilead’s CAR-T treatment Yescarta, which was cleared last month by the FDA for disease that is refractory to one prior therapy or that relapses within 12 months of first-line chemoimmunotherapy. Peak sales in this indication have been pegged at $1.5 billion.