Capivasertib

AstraZeneca’s Truqap (capivasertib) received a positive recommendation from the US FDA’s Oncologic Drugs Advisory Committee (ODAC) for use in patients with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC), a vote that follows the agency’s acceptance of a supplemental New Drug Application (sNDA) in August 2025. The committee voted 7 to 1, with one abstention, in favor of the benefit-risk profile of capivasertib in combination with abiraterone and androgen deprivation therapy (ADT). The ODAC recommendation does not constitute a final FDA approval decision, and the agency is not bound by the committee’s conclusions. The sNDA seeks approval for Truqap in combination with abiraterone and ADT for adult patients with PTEN-deficient mHSPC, a subgroup estimated to represent approximately one in four patients diagnosed with the disease in the US each year. Truqap is administered at 400 mg twice daily on an intermittent schedule of four days on and three days off. AstraZeneca has also submitted a regulatory application for the same indication in the European Union, where it remains under review. The company has not disclosed a specific PDUFA date in connection with the US filing. The submission is supported by results from the CAPItello-281 Phase III trial, a double-blind, randomized, placebo-controlled study that enrolled 1,012 adults with histologically confirmed de novo hormone-sensitive prostate adenocarcinoma and centrally confirmed PTEN deficiency. Patients were randomized to receive either capivasertib plus abiraterone and ADT or placebo plus abiraterone and ADT. The primary endpoint was radiographic progression-free survival (rPFS) as assessed by the investigator. Results from the primary analysis, presented at the 2025 European Society for Medical Oncology Congress and simultaneously published in the Annals of Oncology, showed a statistically significant 19% reduction in the risk of radiographic disease progression or death with the capivasertib combination, corresponding to a hazard ratio of 0.81 (95% CI: 0.66–0.98; p\=0.034). Median rPFS was 33.2 months in the capivasertib arm versus 25.7 months in the comparator arm, a difference of 7.5 months. Secondary endpoints showed consistent directional benefit: time to castration resistance was 29.5 versus 22.0 months (HR 0.77; 95% CI: 0.63–0.94), and symptomatic skeletal event-free survival was 42.5 versus 37.3 months (HR 0.82; 95% CI: 0.66–1.02). PSA progression favored the capivasertib arm with an HR of 0.73 (95% CI: 0.52–1.01). Overall survival data were immature at the time of the primary analysis, though interim results numerically favored the capivasertib combination; the trial is ongoing to assess OS as a key secondary endpoint. The safety profile observed in CAPItello-281 was broadly consistent with the known profiles of each component. Grade 3 or higher adverse events occurred in 67% of patients in the capivasertib arm versus 40.4% in the placebo arm. The most common high-grade events in the capivasertib group included rash (12.3%), hyperglycemia (10.3%), hypokalemia (8.7%), diarrhea (6.2%), hypertension (5.8%), and anemia (5.2%). The filing adds to a growing body of evidence linking PI3K/AKT pathway dysregulation to aggressive prostate cancer biology. PTEN loss, which occurs in roughly one in four patients with mHSPC, removes a key brake on AKT signaling, driving tumor growth and contributing to resistance to androgen receptor pathway inhibition. Capivasertib is a pan-AKT inhibitor targeting all three isoforms — AKT1, AKT2, and AKT3 — and its development in PTEN-deficient prostate cancer is grounded in the hypothesis that blocking this downstream pathway may complement the androgen-deprivation strategies that form the backbone of current standard care. Truqap already holds FDA approval in combination with fulvestrant for hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer with PIK3CA, AKT1, or PTEN alterations, based on results from the CAPItello-291 trial. The prostate cancer filing would constitute a new indication and a mechanistically distinct clinical context, given the combination partner and patient population involved. AstraZeneca is also evaluating capivasertib in a Phase Ib/III breast cancer program, CAPItello-292, which remains in active recruitment. Globally, prostate cancer accounts for more than 1.4 million new diagnoses annually and approximately 397,000 deaths, making it the fifth leading cause of cancer death in men worldwide. In the US, it is the most common cancer in men, with more than 300,000 new cases each year. Among patients diagnosed with metastatic disease, five-year survival rates remain low. PTEN-deficient tumors are associated with a measurably worse prognosis than PTEN-intact disease, and the absence of any approved therapy targeting this subgroup has represented a recognized gap in the treatment landscape. The FDA will issue its final decision independently of the ODAC vote. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

iStock, leolintang Members of the FDA’s Oncologic Drugs Advisory Committee questioned the design of AstraZeneca’s Phase 3 trial of camizestrant, which involved switching treatments at the point of mutation detection, as opposed to the current practice of changing regimens upon disease progression. A panel of independent advisors have recommended against approving AstraZeneca’s oral SERD drug camizestrant for certain breast cancer patients alongside a CDK4/6 inhibitor. The issue, the panelists contended, lies with AstraZeneca’s study design. In the Phase 3 SERENA-6 trial, the pharma opted to switch patients to camizestrant or continue their current treatment schedules at the point of testing for mutations in the ESR1 gene. This is an early point to switch treatment, which usually happens upon disease progression. The committee members worried that an approval could set a precedent for other drugmakers, prompting similar trial designs without necessarily having robust evidence that an earlier switch indeed results in survival gains. “The data for changing the paradigm just isn’t there,” Stanley Lipkowitz, deputy director of the center for cancer research at the National Cancer Institute, said when explaining his ‘no’ vote. “I do agree with the FDA’s concern that all the next trials will do exactly this with no evidence that it’s improving outcomes,” he continued. While noting that he is “very excited” about oral SERDs, he couldn’t “say that we should change fundamentally how we approach patients based on this data.” “If there were an OS [overall survival] benefit, I would have voted yes,” Lipkowitz said. Adcomms Two AstraZeneca Drugs To Be Scrutinized in First FDA Cancer Advisory Panel in 9 Months The FDA’s cancer advisors will discuss AstraZeneca’s application for the oral SERD camizestrant in breast cancer and the AKT inhibitor Truqap in prostate cancer. March 9, 2026 · 3 min read · Tristan Manalac Read more Six of the outside experts voted against AstraZeneca, versus three that came down in support of approval. The panelists were asked to vote on whether camizestrant demonstrated a clinically meaningful benefit in patients who have HR+/HER2- metastatic breast cancer with an ESR1 mutation. For Natalie Compagni Portis, the patient representative on the panel, her ‘no’ vote leaned more heavily on the lack of survival data, which she said could weigh heavily on the psychology of women with breast cancer. “I think it’s an exciting possibility that we could truly change the paradigm and be able to truly assure patients that treating earlier means either living better and/or living longer with metastatic breast cancer. “But I really wonder if we are exploiting the hope of women with metastatic breast cancer,” she continued. “Without evidence of longer overall survival and . . . to have very sparse data on [quality of life], it really seems only speculation and hope.” SERENA-6 showed that patients treated with the camizestrant regimen saw a 56% reduction in the risk of disease progression or death, according to data published in June 2025 in The New England Journal of Medicine . OS data remain immature. “Importantly, the panelists expressed enthusiasm for the potential of biomarker technology and did not question cami’s underlying activity, but were unconvinced by the trial meriting a change in the treatment paradigm,” Leerink Partners wrote in a Thursday evening note. “The panelists’ concerns were focused on the trial design, its endpoints, and its ability to establish clinical benefit. This leaves the door open for other cami programs.” AstraZeneca is developing camizestrant in several other treatment settings for breast cancer, including for frontline care. The FDA raised similar concerns as its outside experts. In a briefing document published earlier this week, internal reviewers pointed out that “the treatment paradigm evaluated in SERENA-6 is new.” “Currently, no drugs have FDA approval for switching treatment in patients based on detection” as opposed to at radiographic progression, the agency documents read. “It is unclear whether changing treatment at this earlier timepoint, prior to radiographic progression, results in long-term benefit.” The FDA does not have to follow the advice of an adcomm, but typically aligns with the experts’ recommendations.