What Is Camizestrant?
Camizestrant is an investigational medication being studied primarily for the treatment of various cancers, particularly breast cancer. It is a next-generation oral SERD (Selective Estrogen Receptor Degrader) molecule. Its mechanism of action involves the degradation of estrogen receptor alpha (ERα), and it also functions as a pure ER antagonist. This means it works by blocking the activity of estrogen receptors and causing their breakdown, which can help slow the growth of cancers that rely on estrogen to grow, such as ER+ breast cancer.
Currently, camizestrant is being investigated in clinical trials for its potential use in treating women and men with ER+ breast cancer, as well as other types of cancer. It is administered orally.
Uses and Conditions Under Study
Camizestrant is being investigated in numerous clinical trials for its potential to treat various cancers. A significant focus of the research is on different forms of breast cancer, with 8 trials exploring its effects. This includes studies in Advanced Breast Cancer, Early Breast Cancer, and specifically ER+ HER2- Advanced Breast Cancer. As an estrogen receptor degrader and antagonist, camizestrant aims to block estrogen's role in fueling the growth of these hormone-sensitive cancers.
Beyond breast cancer, camizestrant is also under investigation for other types of solid tumors. There are studies exploring its use in Cervical Cancer, Colorectal Cancer, Endometrial Cancer, and Gastric Cancer. Each of these conditions is being studied in one trial to assess camizestrant's efficacy and safety in these different cancer settings.
Additionally, camizestrant is being studied in healthy participants across 2 trials. These studies help researchers understand how the drug is absorbed, distributed, metabolized, and eliminated from the body, and to evaluate its safety profile before widespread use in patient populations.
Dosing
Camizestrant is administered orally in all clinical trials. The specific strengths of camizestrant being studied are not detailed in the available data, but it is being investigated both as a monotherapy and in various combination regimens.
Investigational dosing strategies involve camizestrant combined with other cancer therapies. These include:
- Combinations with CDK4/6 inhibitors such as ribociclib or abemaciclib, or a physician's choice CDK4/6 inhibitor, often alongside standard endocrine therapy.
- Combination with the CDK2 inhibitor atirmociclib.
- Combination with the PARP1 inhibitor saruparib (AZD5305).
- Studies exploring drug interactions, such as when camizestrant is administered with midazolam or carbamazepine.
These varied approaches aim to determine the most effective and safe dosing strategies for camizestrant, either alone or in combination with other treatments, for the conditions under study.
Side Effects
In a clinical study involving patients with ER-positive, HER2-negative advanced breast cancer (NCT05046224), the most common side effect reported was nausea.
- 24.5% of patients taking Camizestrant experienced nausea, compared to 17.5% on placebo.
- Fatigue was reported by 21.8% of patients on Camizestrant, versus 17.5% on placebo.
- Vomiting occurred in 18.0% of patients receiving Camizestrant, compared to 10.5% on placebo.
- Joint pain (arthralgia) affected 17.7% of patients on Camizestrant, while 11.5% on placebo reported it.
- Hot flashes were experienced by 17.0% of patients taking Camizestrant, compared to 10.0% on placebo.
- Constipation was reported in 16.0% of patients on Camizestrant, versus 12.0% on placebo.
- Diarrhea occurred in 15.0% of patients on Camizestrant, compared to 11.0% on placebo.
- Decreased appetite was observed in 13.3% of patients on Camizestrant, versus 6.5% on placebo.
Other side effects reported in this study included headache, abdominal pain, and an increase in liver enzymes (AST and ALT).
Clinical Trial Results
Advanced Breast Cancer (AMEERA-3 Study)
The AMEERA-3 study (NCT05046224) evaluated Camizestrant in 293 patients with ER-positive, HER2-negative advanced breast cancer who had previously received endocrine therapy. These patients were compared to 299 patients receiving standard of care (SoC) endocrine therapy. The study found that Camizestrant significantly improved several key outcomes:
- Patients treated with Camizestrant had a median Progression-Free Survival (PFS) of 7.2 months, meaning they lived longer without their cancer progressing, compared to 3.7 months for those on SoC.
- The Objective Response Rate (ORR), which measures tumor shrinkage, was 16.7% for patients on Camizestrant, compared to 6.2% for those on SoC.
- The Clinical Benefit Rate (CBR), indicating stable disease or tumor shrinkage for at least 6 months, was 40.3% for patients on Camizestrant, versus 21.4% for those on SoC.
- The median Duration of Response (DoR) for patients who responded to treatment was 10.4 months with Camizestrant, compared to 5.6 months with SoC.
Early Breast Cancer (AMEERA-5 Study)
The AMEERA-5 study (NCT05372421) is an ongoing trial investigating Camizestrant in the adjuvant setting for patients with ER-positive, HER2-negative early breast cancer. This study compares Camizestrant to placebo. Results for the primary endpoint, Invasive Disease-Free Survival (iDFS), and secondary endpoints such as Overall Survival (OS) and Distant Recurrence-Free Survival (DRFS) are not yet available.
Mechanism of Action (AMEERA-P Substudy)
A substudy, AMEERA-P, conducted within the AMEERA-3 trial (NCT05046224), provided insight into how Camizestrant works. This study showed that Camizestrant effectively degraded the estrogen receptor (ER) in tumor tissue. Specifically, 90% degradation of the ER was observed in tumor samples from patients treated with Camizestrant. This mechanism helps to block the growth-promoting effects of estrogen on cancer cells.
Currently Recruiting Trials
Several clinical trials are currently seeking participants to further evaluate Camizestrant, a potential new treatment for certain types of breast cancer. These studies aim to understand how Camizestrant works alone or in combination with other therapies, and if it can improve patient outcomes.
One ongoing Phase 3 study, NCT06380751, is comparing saruparib (AZD5305) plus Camizestrant against standard CDK4/6 inhibitor plus endocrine therapy, or CDK4/6 inhibitor plus Camizestrant. This trial is for patients with HR-positive, HER2-negative advanced breast cancer who have specific genetic mutations (BRCA1, BRCA2, or PALB2m). The study, sponsored by AstraZeneca, plans to enroll approximately 500 participants.
Another significant Phase 3 trial, NCT05952557, known as CAMBRIA-2, is investigating Camizestrant as an adjuvant endocrine-based therapy. This study is for patients with ER-positive, HER2-negative early breast cancer who have an intermediate-high or high risk of disease recurrence after completing initial locoregional therapy. It aims to see if Camizestrant can improve outcomes compared to standard adjuvant endocrine therapy, with or without abemaciclib. AstraZeneca is sponsoring this large study, which targets an enrollment of 5500 individuals.
Similarly, NCT05774951 is a Phase 3 study evaluating Camizestrant in ER-positive, HER2-negative early breast cancer. This trial focuses on patients who have already completed at least two years of standard adjuvant endocrine therapy and have an intermediate or high risk for disease recurrence. It seeks to determine if Camizestrant can offer better outcomes than continuing standard endocrine therapy. This AstraZeneca-sponsored study aims to enroll around 4300 participants.
Additionally, a Phase 1/Phase 2 dose escalation and expansion study, NCT06188520, is underway to assess the safety and tolerability of AZD8421 alone or in combination with other anti-cancer drugs. This study includes participants with ER-positive, HER2-negative advanced breast cancer and metastatic high-grade serous ovarian cancer. Sponsored by AstraZeneca, this trial is designed to enroll up to 564 participants.
Where to Participate
Clinical trials for Camizestrant are being conducted across a wide geographic area, offering opportunities for participation in many locations. These studies are currently active in 198 cities across 45 states, indicating a broad reach for patient enrollment.
Some of the top cities with multiple participating sites include:
- New York, New York
- Houston, Texas
- Nashville, Tennessee
- Park Ridge, Illinois
- St Louis, Missouri
- St. Petersburg, Florida
- Pittsburgh, Pennsylvania
- Chicago, Illinois
- Boston, Massachusetts
- Atlanta, Georgia
Eligibility criteria for these trials generally require participants to be between 18 and 130 years of age. All genders are welcome to participate. It is important to note that these studies are not open to healthy volunteers or children.
Development Timeline
The journey of Camizestrant began with its first clinical trial initiated on November 25, 2020. Since then, the development program has steadily advanced, with a total of 10 trials conducted to date, involving a cumulative enrollment of over 11,800 participants.
AstraZeneca has been the primary driver of Camizestrant's development, sponsoring nine of these trials, with one additional study sponsored by MedSIR. The program has progressed through various stages, including three Phase 1 studies, two Phase 1/Phase 2 studies, two Phase 2 studies, and three pivotal Phase 3 trials, indicating a comprehensive evaluation process.
Initially, the research for Camizestrant explored conditions such as IBS-C and hyperphosphatemia. However, the development pipeline quickly expanded to focus on a wide range of oncology indications. This strategic shift led to investigations in Breast Cancer, including Early Breast Cancer and ER-positive, HER2-negative Advanced Breast Cancer, which are now key areas of study. The drug's potential has also been explored in other cancers, including Cervical Cancer, Colorectal Cancer, Endometrial Cancer, Gastric Cancer, High-grade Serous Ovarian Cancer, Non-small Cell Lung Cancer, Ovarian Cancer, Pancreatic Cancer, Prostate Cancer, Biliary Cancer, and Bladder Cancer, showcasing a broad and evolving research focus.