A phase 2 study of Pfizer’s atirmociclib has hit its primary endpoint, providing evidence that the CDK4 inhibitor improves progression-free survival (PFS) in second-line metastatic breast cancer. But the Big Pharma is already looking past the setting, with its sights now locked onto earlier lines of treatment.
Pfizer originally designed Fourlight-1 as a phase 3 trial. However, the drugmaker rethought its strategy last year, cutting the enrollment target from 500 to 333 and redesignating the study as a phase 2 trial. Pfizer made the changes around the time that it began a phase 3 trial that is enrolling more than 1,000 patients with first-line advanced or metastatic breast cancer.
While racing to seize the first-line opportunity ahead of BeOne Medicines, Pfizer kept studying its CDK4 inhibitor in the slimmed-down Fourlight-1 trial. Investigators gave atirmociclib and fulvestrant, which AstraZeneca sells as Faslodex, to people with HR-positive, HER-negative advanced or metastatic breast cancer. Patients had previously received a CDK4/6 inhibitor.
PFS was significantly longer on Pfizer’s investigational regimen than on the combination of fulvestrant or everolimus plus exemestane, achieving the phase 2 trial’s primary endpoint. Pfizer said the PFS results were consistent across all prespecified subgroups. Overall survival data were immature at the time of the analysis. The safety and tolerability data were free from surprises, according to Pfizer.
Related
Jeff Legos, Ph.D., chief oncology officer at Pfizer, said in a statement that the data reinforce his confidence that atirmociclib may meaningfully differentiate from CDK4/6 inhibitors, the standard of care in HR-positive breast cancer. The potential to improve on the standard of care informed Pfizer’s decision to prioritize the first-line setting, where atirmociclib is going head-to-head with approved CDK4/6 inhibitors.
Investigators can choose Eli Lilly’s Verzenio, Novartis’ Kisqali or Pfizer’s Ibrance for patients in the control arm of the phase 3 trial of atirmociclib in first-line breast cancer. With atirmociclib’s safety profile supporting uninterrupted dosing, Pfizer CEO Albert Bourla, Ph.D., called (PDF) the CDK4 program “a huge opportunity for a mega blockbuster” at the J.P. Morgan Healthcare Conference in January.
BeOne is pursuing the same opportunity. Emboldened by phase 1 data, the biotech plans (PDF) to start a phase 3 trial of its rival CDK4 inhibitor BGB-43395 in first-line HR-positive breast cancer in the first half of the year. Like Pfizer, BeOne is pitting its candidate against the investigator’s choice of CDK4/6 inhibitor.
