'Marked’ for Stardom?: Truqap

Ushering in a first-in-class therapeutic approach in oncology, the FDA, in November 2023, approved AstraZeneca’s Truqap (capivasertib) in combination with Faslodex (fulvestrant) for treating adults with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1 or PTEN).

HR-positive breast cancer is currently the most common subtype of breast cancer, as approximately 65% of breast cancer tumors have been given this classification. Additionally, mutations in PIK3CA and AKT1 and alterations in PTEN have affected around half of patients with advanced HR-positive breast cancer. Considered a limited distribution drug and specialty medication, Truqap was launched in the commercial market earlier this year and reportedly generated $92 million in sales in the second quarter.

In a January video interview, Pharmaceutical Executive spoke with Ashley Gaines, VP, head of breast cancer franchise, US oncology business unit, AstraZeneca, to discuss the approval of Truqap and its significance as a novel treatment for HR-positive HER2-negative locally advanced or metastatic breast cancer.

“Within this form of breast cancer, there’s a significant need for new treatment options after they progress on therapy for metastatic disease, and that’s where Truqap comes in,” said Gaines. “Truqap in combination with fulvestrant is now approved for patients who have progressed on initial therapy from biomarkers PIK3CA, AKT1, or PTEN. What’s exciting here is that this combination brings a new mechanism of action to the second-line setting, which is addressing a critical unmet need in this space. It brings a medicine that offers both compelling efficacy and a compelling benefit risk profile.”

Prior to Truqap, AZ has had many breast cancer medicines approved - Enhertu in HER2+ and HER2-low breast cancer, Lynparza in early and metastatic breast cancer as well as older breast cancer medicines such as Faslodex and Zoladex.

“Our ambition at AstraZeneca is to eliminate breast cancer as a cause of death one day. As part of that ambition, we hope to bring medicines to the market that will increase survival,” Gaines told Pharm Exec. “With Truqap, we saw in the [Phase III] CAPItello-291 study a 50% disease reduction or death, which is really exciting. Our overall data at the time of the data readout was immature but encouraging.”

In June of this year, Truqap also received approval in Europe for adult patients with estrogen receptor-positive, HER2‑negative locally advanced or metastatic breast cancer with one or more PIK3CA, AKT1, or PTEN-alterations following recurrence or progression on or after an endocrine-based regimen.

The approval momentum for Truqap was tempered some with news in June surrounding efforts to expand the drug’s indication. In results released from the Phase III CAPItello-290 trial evaluating Truqap in combination with paclitaxel as a treatment for patients with metastatic triple-negative breast cancer, the trial failed to meet its primary efficacy endpoints of improving overall survival compared to paclitaxel with a placebo. Amid the setback, Susan Galbraith, AstraZeneca’s executive vice president of oncology R&D, reaffirmed the company’s commitment to advancing science for particularly difficult-to-treat heterogeneous subtypes of breast cancer, such as triple-negative.

“While we are disappointed in the CAPItello-290 outcome, these results will further our understanding of the role of the PI3K/AKT pathway in breast cancer as we continue our clinical research across the Truqap clinical development program and across our pipeline,” she said in a press release.

In the January interview with Pharm Exec, Gaines discussed the CapItello program as a whole, which is investigating Truqap’s utility in several other indications and tumor types.

“We’re also further studying it in hormone receptive-positive breast cancer,” she said. “We have a study underway where we’re looking at a combination of capivasertib CDK46-inhibitors and fulvestrant. We also have two studies underway in prostate cancer and we’re excited to see what the treatment can do as we expand into other tumor types as well.”