While AstraZeneca’s Truqap bears the distinction of being the first AKT inhibitor to pass muster with the U.S. FDA, the U.K.-based drugmaker is struggling in its efforts to expand the cancer med’s label.
In the late-stage CAPItello-290 study, Truqap plus the chemotherapy paclitaxel failed to help extend the lives of patients with locally advanced or metastatic triple-negative breast cancer (TNBC) over paclitaxel and placebo alone, AZ said Tuesday.
The 923-patient trial was assessing the Truqap-chemo cocktail as a potential first line treatment in certain TNBC patients. The study specifically assessed a dual primary endpoint of improvement in overall survival (OS) in both the general trial population and a subgroup of patients whose tumors harbor PIK3CA, AKT1 or PTEN biomarker alterations, AZ explained.
The clinical misfire follows Truqap’s approval as the first FDA-endorsed AKT inhibitor back in November. The drug was approved in tandem with AZ’s Faslodex to treat certain patients with HR-positive, HER2-negative advanced breast cancer.
But unfortunately for AZ, the greenlight came with a restrictive label.
To be eligible for the therapy, a patient’s cancer must bear at least one of the same three gene alterations covered in the latest trial’s subgroup, plus, the patient’s disease must have either progressed on at least one endocrine-based regimen in the metastatic setting or recurred within a year of completing postsurgical adjuvant therapy.
While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factory receptor 2 (HER2), TNBC is defined as negative for all three, AZ explained in its Tuesday release.
Moreover, mutations in PIK3CA and AKT1, and alterations in PTEN affect roughly 35% of patients with TNBC, the company added.
“We are committed to advancing science for patients in some of the most challenging cancers, including this heterogeneous subtype of breast cancer,” Susan Galbraith, EVP of oncology R&D at AstraZeneca, said in a Tuesday statement. “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 programme and across our pipeline.”
One silver lining for AstraZeneca? The safety profile of the Truqap-paclitaxel combo was largely on par with the known profile of each individual medicine, with no new safety signals identified, AZ said.
The company added that it will share full results from the trial “in due course.”
Despite the miss in TNBC, AstraZeneca continues to test Truqap combinations across a range of cancers.
The phase 3 CAPItello-292 study, for instance, is looking at Truqap plus Faslodex and CDK4/6 inhibitors in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative locally advanced, unresectable or metastatic breast cancer.
Plus, Truqap is being tested in prostate cancer in combination with docetaxel and J&J's prostate cancer med Zytiga (abiraterone) in the phase 3 CAPItello-280 and CAPItello-281 studies, respectively.
Overall, Truqap reeled in $50 million during the first quarter of 2024, which was the med’s first full earnings period on the market.