That research, published in Cancer Cell in October, identified several mechanisms of resistance, including CCNE1 expression, MYC expression, and WNT signaling. Pfizer researchers developed the CDK2/4/6 drug PF3600 based on findings from a study that delved into the mechanisms of resistance to Ibrance. "Inhibition of CDK2, delivered with a CDK2 selective activity drug or a triple activity CDK 2/4/6 agent, may prevent, delay, or reverse resistance and prolong survival." "Most patients with advanced or metastatic breast cancer eventually develop resistance to both endocrine and CDK4/6 inhibitors despite their transformative efficacy," Dolsten said. These patients had advanced or metastatic HR-positive, HER2-negative breast cancer and had received or progressed on prior CDK4/6 inhibitors and endocrine therapy. That study involves previously treated patients with HR-positive, HER2-negative breast cancer triple-negative breast cancer ovarian cancer fallopian tube cancer primary peritoneal cancer and non-small cell lung cancer.Įarly data from that trial, presented in the investor call, showed two patients had confirmed partial responses on PF-07104091 monotherapy. In another Phase I/II trial, Pfizer is studying its CDK2 candidate PF-07104091 as a single agent and in several combination regimens, including with endocrine therapy, Ibrance, and aromatase inhibitors. In early data from 33 patients with metastatic HR-positive, HER2-negative breast cancer in that study, there were three confirmed partial responses and three patients who maintained stable disease for more than 12 months on treatment, Dolsten noted in the investor call.
The trial involves heavily pretreated patients with HR-positive, HER2-negative breast cancer who have received a CDK4/6 inhibitor triple-negative breast cancer platinum-resistant epithelial ovarian cancer fallopian tube cancer and primary peritoneal cancer. In the Phase II study of PF3600, Pfizer is studying the drug as a single agent and in combination with endocrine therapy in several cancer types. "Given strong mechanistic rationale and encouraging preliminary clinical data to date, we believe that the CDK portfolio has the potential to address a broad set of breast cancer patients, both in the first-line HR-positive, HER2-negative metastatic breast cancer setting, as well as expanding to patients in the, post-CDK4/6 inhibitor setting where the unmet need is extremely high," the Pfizer spokesperson said. In 2021, the drug earned $5.44 billion in global sales, a 1 percent increase from its sales in 2020 which were $5.39 billion.
Ibrance, which has been on the market for seven years, is approved in the US to treat hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer plus an aromatase inhibitor as initial endocrine-based therapy in postmenopausal women or in men and with fulvestrant in patients with disease progression following endocrine therapy. Pfizer is betting that PF3600 and PF-07104091 will bolster its CDK inhibitor franchise, which is currently dominated by the blockbuster Ibrance, the firm's top-selling oncology drug. If the studies of these two drugs are successful, Pfizer sees "the potential for breakthrough therapies with significant revenue opportunity," a company spokesperson said over email.
In its Q4 earnings call in March, Pfizer CSO Mikael Dolsten provided an update on ongoing studies of the two CDK inhibitors and estimated that a Phase II trial of PF3600 would wrap up by year-end and a Phase I/II trial of PF-07104091 would be completed in Q2 2023. The company is studying two next-gen CDK inhibitors in breast cancer and other tumor types: the triple-activity agent targeting CDK2/4/6, dubbed PF-06873600 (or PF3600 for short) and the CDK2 inhibitor PF-07104091. Pfizer, a major player developing next-generation CDK inhibitors, is exploring combination treatment strategies with its blockbuster CDK4/6 inhibitor Ibrance (palbociclib) for the treatment of hormone receptor-positive, HER2-negative breast cancer. NEW YORK – Drugmakers and researchers are looking to the next generation of breast cancer treatments, used alone or in combination with existing therapies, in the hopes of overcoming acquired resistance to CDK4/6 inhibition.