The antibody-drug conjugate (ADC) Adcetris has given Pfizer’s oncology department its first pivotal trial win from the legacy Seagen portfolio since the $43 billion merger.
Adcetris, which is known as a standard of care in classical Hodgkin lymphoma, has shown it could work in diffuse large B-cell lymphoma (DLBCL), a common type of non-Hodgkin lymphoma, in a phase 3 trial coded ECHELON-3.
The Pfizer- and Takeda-partnered drug, used in combination with lenalidomide and rituximab, significantly extended patients’ lives compared with the latter two drugs alone in DLBCL patients who had tried at least two prior lines of therapy, Pfizer said Tuesday. The patients were ineligible for stem cell transplant or CAR-T therapy.
Besides meeting the primary endpoint of overall survival, ECHELON-3 also found that the Adcetris triplet significantly delayed tumor progression and was able to trigger more tumor responses compared with the two-drug regimen.
Detailed data from the study will be shared at a medical meeting, and Pfizer will discuss potential submission with the FDA, potentially expanding Adcetris into DLBCL. First approved by the FDA in 2011, the CD30-directed ADC is currently allowed in classical Hodgkin lymphoma and certain T-cell lymphomas.
ECHELON-3 is the third phase 3 study to show an overall survival benefit for an Adcetris combination, Roger Dansey, M.D., chief development officer of Pfizer’s oncology unit, said in a statement Tuesday.
Back in 2022, Adcetris bolstered its case as a standard first-line treatment in advanced-stage classical Hodgkin lymphoma after the phase 3 ECHELON-1 trial showed that an Adcetris combo significantly cut the risk of death by 41% compared with a chemo regimen called ABVD. For that regimen, Adcetris replaces the chemotherapy bleomycin to be used alongside doxorubicin, vinblastine and dacarbazine.
Adcetris joined Pfizer via the Seagen merger already an established blockbuster, Pfizer’s oncology chief, Chris Boshoff, M.D., Ph.D., said during a recent investor event. Thanks to a reporting gap caused by the merger, Adcetris’ full-year 2023 sales were unclear. Under Seagen’s stewardship, Adcetris saw sales rise 25% year over year to $751 million in the first nine months of 2023.
Adcetris uses the same “vedotin” payload as other ADCs in Pfizer’s portfolio. Pfizer believes ADCs based on this payload could combine well with PD-1 inhibitors because it can drive immunogenic cell death. The company’s Astellas-partnered Nectin-4 ADC Padcev already demonstrated unprecedented efficacy when combined with Merck’s Keytruda in bladder cancer.
In December, researchers provided updated midstage data showing promise for Adcetris’ combination with Bristol Myers Squibb’s PD-1 blocker Opdivo, plus doxorubicin and dacarbazine, in first-line classical Hodgkin lymphoma. The readout came after Opdivo beat Adcetris on progression-free survival in a head-to-head study.
It’s not clear whether Pfizer plans to move the PD-1 combo concept into phase 3 testing for Adcetris. Previously, BMS' CheckMate-812 trial for the Adcetris-Opdivo pairing in previously treated classical Hodgkin lymphoma was terminated due to insufficient enrollment.
Meanwhile, Pfizer is working on a next-generation CD30-targeted ADC with the potential for an improved therapeutic window compared with Adcetris. With positive results from preclinical models, including in Adcetris-resistant tumors, Pfizer plans to move the new ADC into phase 1 testing this year.
Overall, Pfizer is targeting at least eight blockbuster cancer drugs by 2030 following the Seagen merger.