AstraZeneca’s Camizestrant Hit by FDA Advisory Committee Vote While Truqap Moves Ahead

WHO is investigating both exposure source and transmission route, including whether the first infection occurred off the vessel and whether close-contact spread played a role. 

AstraZeneca received feedback from the FDA’s Oncologic Drugs Advisory Committee (ODAC) on two oncology drug applications this week, one involving its investigational breast cancer drug camizestrant and the other involving Truqap (capivasertib), an approved targeted therapy.

ODAC voted against the benefit-risk profile of camizestrant for advanced breast cancer involving ESR1 mutations, but backed a proposed Truqap expansion for prostate cancer marked by PTEN deficiency.

The FDA is not required to follow the committee’s recommendations, but it considers ODAC’s advice when reviewing cancer drug applications.

Camizestrant Combination Faces Negative FDA ODAC Vote

ODAC voted three to six against the benefit-risk profile of camizestrant used with a CDK4/6 inhibitor for patients with HR-positive, HER2-negative advanced breast cancer whose tumors had developed an ESR1 mutation.

ESR1 mutations can make breast cancer less responsive to endocrine therapy, a treatment approach that blocks or lowers estrogen signaling. The proposed use is in the first-line setting, meaning before patients have moved on to later lines of treatment for advanced disease.

Camizestrant is an investigational oral selective estrogen receptor degrader, or SERD. These drugs are designed to block and break down estrogen receptors, which can help slow the growth of some HR-positive breast cancers.

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The camizestrant application is supported by the Phase III SERENA-6 trial, which enrolled 315 adults receiving first-line treatment with an aromatase inhibitor and a CDK4/6 inhibitor.

The SERENA-6 trial used circulating tumor DNA, or ctDNA, testing to look for ESR1 mutations before disease progression appeared on routine scans. If a mutation was detected, patients switched from an aromatase inhibitor to camizestrant while staying on the same CDK4/6 inhibitor.

In a planned interim analysis, the camizestrant combination reduced the risk of disease progression or death by 56% compared with continued aromatase inhibitor treatment plus a CDK4/6 inhibitor. Median progression-free survival was 16.0 months with the camizestrant combination, compared with 9.2 months in the control group.

Overall survival data were still maturing. AstraZeneca said the safety profile was consistent with the known profiles of the individual medicines and that no new safety concerns were identified.

Camizestrant is not approved for this use. AstraZeneca said it will continue working with the FDA as the agency completes its review.

FDA Advisory Committee Backs Truqap Combination in Prostate Cancer

Truqap’s ODAC review landed differently. The already approved AstraZeneca drug is being considered for a new prostate cancer use, towards a potential label expansion.

ODAC voted seven to one, with one abstention, in favor of Truqap for this proposed prostate cancer use. The review covers Truqap with abiraterone and androgen deprivation therapy for patients whose tumors have PTEN deficiency, which likely makes the cancer more aggressive.

The combination includes hormone-targeting treatments that lower or block androgen signals, which can fuel prostate cancer growth.

PTEN deficiency refers to the loss or reduced function of PTEN, a tumor suppressor gene. AstraZeneca described PTEN-deficient metastatic hormone-sensitive prostate cancer as an aggressive form of the disease with limited treatment options. The company said that about one in four patients with metastatic hormone-sensitive prostate cancer have this form of the disease.

The proposed expansion is supported by the Phase III CAPItello-281 trial.

In the trial’s main analysis, Truqap plus abiraterone and androgen deprivation therapy reduced the risk of cancer worsening on scans or death by 19% compared with abiraterone and androgen deprivation therapy plus placebo.

Median radiographic progression-free survival was 33.2 months with the Truqap combination, compared with 25.7 months in the control group. Radiographic progression-free survival refers to how long patients live without their cancer worsening on imaging scans.

Overall survival data were not mature, and the trial will continue to assess survival as a key secondary endpoint.

Both camizestrant and Truqap applications remain under FDA review.

In ESR1-mutated breast cancer developments, the FDA just approved Arvinas and Pfizer’s Veppanu (vepdegestrant) for adults with ER-positive, HER2-negative advanced breast cancer with an ESR1 mutation after the disease progressed following at least one hormone-based treatment. Veppanu, a PROteolysis TArgeting Chimera (PROTAC), is an oral drug designed to break down estrogen receptors, which can help slow cancers that use estrogen signaling to grow. In the Phase III VERITAC-2 trial, vepdegestrant reduced the risk of disease progression or death by 43% versus fulvestrant, an injectable estrogen receptor-blocking treatment.