Pfizer and Arvinas’ targeted protein degrader plus Ibrance has shown promising efficacy in breast cancer patients in updated data from an early-stage trial, raising anticipation for a pair of ongoing Phase 3 studies.
The updated Phase 1b results showed vepdegestrant plus Ibrance delivered a 41.9% overall response rate (ORR) and 11.2 months of median progression-free survival (PFS). The trial enrolled patients with pre-treated locally advanced or metastatic breast cancer that is estrogen receptor-positive (ER+) and human epidermal growth factor 2 negative (HER2-).
Thursday’s data were presented at the European Society for Medical Oncology’s annual congress on breast cancer. Arvinas’ share price $ARVN increased 3.4% to $33.43 Thursday morning.
The new data add to those unveiled in December. The interim readout showed a 42% ORR and 11.1-month median PFS at an average follow-up period of 11 months. Earlier this month, TD Cowen analysts said the original data show an improvement over CDK4/6 inhibitors plus endocrine therapy, a traditional treatment regimen that offers four to five-month median PFS.
The Phase 1b trial, which recruited 46 participants, followed patients for a further six months with a December 18 cutoff date, according to a company release. In the secondary efficacy endpoints, subjects will be followed through to study completion, which is around two years, according to clinicaltrials.gov.
The combination was associated with high-grade cases of neutropenia (91%) and decreased white blood cell count (15%). The majority of high-grade neutropenia events dropped off after the dose of Ibrance was reduced according to the drug’s label, Arvinas said. The biotech added that there were no patient deaths or febrile neutropenia events.
Roger DanseyVepdegestrant is in two Phase 3 trials — one as a monotherapy for second-line breast cancer and another in combination with Ibrance for first-line breast cancer. Pfizer said the monotherapy trial is set to read out in the second half of the year.
Pfizer licensed vepdegestrant from Arvinas in a 2021 deal with $650 million upfront and up to $1.4 billion in biobucks. Pfizer’s Chief Development Officer for oncology Roger Dansey said in the Thursday release that it wants to establish vepdegestrant as “a new standard-of-care endocrine therapy backbone” for patients with ER+/HER2- breast cancer.
Vepdegestrant was developed using Arvinas’ PROTAC technology, which enables drugs to “act in a catalytic fashion” and trigger “sequential degradation of several copies of the target protein.”