Camizestrant for Breast Cancer

(CAMBRIA-2 Trial)

Recruiting at 730 trial locations

Overseen By AstraZeneca Breast Cancer Study Locator Service

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: SERDs, Fulvestrant, LHRH agonists

Disqualifiers: Metastatic cancer, Heart failure, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 7 years

5500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether camizestrant, a hormone therapy, can improve outcomes for individuals with early-stage breast cancer that is estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-). The trial compares camizestrant to standard hormone therapies to determine which more effectively prevents cancer recurrence after surgery and possibly other treatments. It includes two groups: one receiving standard hormone therapy and the other receiving camizestrant, with or without an additional drug called abemaciclib. Individuals who have completed surgery for breast cancer and have not experienced disease spread may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to advancing breast cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain hormone therapies or anti-cancer treatments not mentioned in the protocol, except for bisphosphonates or RANKL inhibitors.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that camizestrant, the treatment in this trial, has been studied for its safety in people. Earlier studies found that camizestrant has a tolerable safety profile, meaning most people could take the treatment without experiencing serious side effects.

This treatment is a type of drug known as a selective estrogen receptor degrader (SERD). It works by blocking estrogen receptors, proteins that can help some breast cancers grow. By blocking these receptors, camizestrant can help stop the cancer from growing.

While detailed safety data from the current phase are not yet available, testing camizestrant in a later phase of clinical trials suggests some confidence in its safety. Treatments usually need to show good safety results in earlier studies before advancing to later phases. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Camizestrant is unique because it targets estrogen receptors in a new way, offering a fresh approach to treating breast cancer. Unlike standard endocrine therapies like aromatase inhibitors or tamoxifen, camizestrant is a selective estrogen receptor degrader (SERD), which may help overcome resistance that some patients develop with current treatments. Researchers are excited about its potential to provide a more effective option for those who may not respond well to existing therapies.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research has shown that camizestrant, which participants in this trial may receive, is a promising treatment for ER+ breast cancer. It blocks and breaks down the estrogen receptors that help cancer grow. Studies have found that camizestrant effectively fights tumors, whether used alone or with other cancer drugs. This trial will compare camizestrant, with or without abemaciclib, to standard endocrine therapy of the investigator's choice, with or without abemaciclib. Overall, early results suggest camizestrant may be a good option for preventing cancer from returning. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with ER+/HER2- early-stage breast cancer that's been surgically removed, without signs of spreading. They should have finished primary treatment and can join within a year of surgery. Prior short-term endocrine therapy is okay. Participants need to be in good health with proper organ function.

Inclusion Criteria

My breast cancer is early-stage, ER+ and HER2-, with no signs of spreading.

I have completed treatment for my breast cancer, including surgery and possibly chemotherapy.

My organs and bone marrow are working well.

Exclusion Criteria

My breast cancer cannot be removed by surgery and has spread.

I am currently on hormone therapy for conditions not related to cancer.

I have been cancer-free for at least 5 years, except for certain low-risk types.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive camizestrant or standard endocrine therapy with or without abemaciclib for 7 years

7 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Camizestrant

Trial Overview The study compares the effectiveness of Camizestrant against standard adjuvant endocrine therapies like Tamoxifen, Anastrozole, Letrozole, Exemestane, or Abemaciclib over 7 years in preventing breast cancer recurrence after initial treatment.

How Is the Trial Designed?

Group I: Arm B: camizestrant ± abemaciclib Experimental Treatment 2 Interventions

camizestrant ± abemaciclib

Group II: Arm A: standard endocrine therapy of investigator´s choice ± abemaciclib Active Control 5 Interventions

standard endocrine therapy of investigator's choice (aromatase inhibitors \[AI; exemestane, letrozole, anastrozole\] or tamoxifen) ± abemaciclib

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Austrian Breast and Colorectal Cancer Study Group (ABCSG)

Collaborator

Trials

1

Recruited

5,500+

Published Research Related to This Trial

In a presurgical study involving 46 women with ER+ HER2- breast cancer, AZD9496, an oral selective estrogen receptor degrader (SERD), demonstrated biological activity by reducing estrogen receptor (ER) levels, but was not superior to fulvestrant, the standard injectable SERD, in efficacy.

Both AZD9496 and fulvestrant effectively reduced progesterone receptor (PR) and Ki-67 levels, indicating their impact on tumor biology, but no new safety concerns were identified, suggesting that AZD9496 is safe to use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Presurgical, Window-of-Opportunity Study Comparing the Pharmacodynamic Effects of the Novel Oral SERD AZD9496 with Fulvestrant in Patients with Newly Diagnosed ER+ HER2- Primary Breast Cancer. Robertson, JFR., Evans, A., Henschen, S., et al.[2021]

Camizestrant, an oral selective estrogen receptor degrader (SERD), shows strong antitumor activity in estrogen receptor-positive (ER+) breast cancer, effectively degrading the estrogen receptor and inhibiting cancer cell growth in both wild-type and mutant models.

When combined with CDK4/6 inhibitors and PI3K/AKT/mTOR-targeted therapies, camizestrant enhances antitumor effects, making it a promising option for overcoming resistance to current endocrine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Next-Generation Oral Selective Estrogen Receptor Degrader Camizestrant (AZD9833) Suppresses ER+ Breast Cancer Growth and Overcomes Endocrine and CDK4/6 Inhibitor Resistance. Lawson, M., Cureton, N., Ros, S., et al.[2023]

Capivasertib is a novel AKT inhibitor that has shown promising efficacy in treating breast cancer, particularly in tumors with specific genetic alterations, and is more effective when combined with other treatments like paclitaxel and fulvestrant.

The recommended dosing schedule for capivasertib is 480 mg twice daily for four days followed by three days off, with manageable side effects including hyperglycemia and diarrhea, indicating a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"The emerging role of capivasertib in breast cancer". Andrikopoulou, A., Chatzinikolaou, S., Panourgias, E., et al.[2022]

Capivasertib, an oral AKT inhibitor, was well tolerated when combined with weekly paclitaxel in patients with advanced ER+/HER2- breast cancer, with a recommended dosing schedule of 400 mg twice daily for 4 days on and 3 days off.

However, the addition of capivasertib did not significantly improve progression-free survival compared to placebo, with median PFS of 10.9 months for capivasertib versus 8.4 months for placebo in the overall population, indicating it may not enhance treatment outcomes in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population. Turner, NC., Alarcón, E., Armstrong, AC., et al.[2023]

The phase II SERENA-2 trial indicates that camizestrant, an investigational oral selective estrogen receptor degrader, significantly prolongs progression-free survival compared to standard treatment with fulvestrant in postmenopausal women with advanced estrogen receptor-positive, HER2-negative breast cancer.

Camizestrant showed superior efficacy in specific patient subgroups, including those who had previously received a CDK4/6 inhibitor, had visceral metastases, or had ESR1 mutations, suggesting it may be particularly beneficial for these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second Oral SERD Shines in ER+ Breast Cancer. [2023]

The SERENA-6 study is investigating the effectiveness of camizestrant, a next-generation oral selective estrogen receptor degrader, in patients with hormone-receptor-positive advanced breast cancer who have developed ESR1 mutations, which often lead to resistance against standard therapies.

The study aims to switch patients from aromatase inhibitors to camizestrant upon detecting ESR1 mutations in circulating tumor DNA, with the goal of improving progression-free survival and delaying the need for chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. Turner, N., Huang-Bartlett, C., Kalinsky, K., et al.[2023]

In the FLIPPER trial, the combination of palbociclib and fulvestrant significantly improved progression-free survival (PFS) in postmenopausal women with HR+/HER2- advanced breast cancer compared to placebo and fulvestrant.

Patient-reported outcomes indicated that while global health status and quality of life (QoL) were maintained during treatment with palbociclib/fulvestrant, the time to deterioration in QoL was longer with placebo/fulvestrant, suggesting that palbociclib/fulvestrant is a beneficial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. Tibau, A., Martínez, MT., Ramos, M., et al.[2023]

Capivasertib, when added to fulvestrant, significantly improves progression-free survival (10.3 months vs. 4.8 months) and overall survival (29.3 months vs. 23.4 months) in women with aromatase inhibitor-resistant ER-positive, HER2-negative advanced breast cancer, based on a study of 140 participants.

The treatment appears to be particularly effective in patients with tumors that have alterations in the PI3K/AKT/PTEN pathway, showing a median progression-free survival of 12.8 months compared to 4.6 months for those receiving placebo in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. Howell, SJ., Casbard, A., Carucci, M., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38729567/

A phase I dose escalation and expansion trial of the next- ... Camizestrant is a next-generation oral selective ER antagonist and degrader (SERD) and pure ER antagonist with a tolerable safety profile.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10690091/

The Next-Generation Oral Selective Estrogen Receptor ... Overall, camizestrant shows strong and broad antitumor activity in ER+ breast cancer as a monotherapy and when combined with CDK4/6i and PI3K/AKT/mTORi.

3. newdrugapprovals.org newdrugapprovals.org/2022/08/24/camizestrant-azd-9833/

Camizestrant, AZD 9833 - New Drug Approvals This can help stop or slow the growth of hormone receptor breast cancer. Researchers think that AZD9833 with palbociclib might work better than ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT362378

Serena-1: Updated analyses from a phase 1 study (parts C ... Results: As of 9 September 2021, 25 patients had received camizestrant 75 mg QD in combination with palbociclib. Tolerability of the combination of camizestrant ...

5. ufhealth.org ufhealth.org/clinical-trials/an-adjuvant-endocrine-based-therapy-study-of-camizestrant-azd9833-in-er-her2-early-breast-cancer

An Adjuvant Endocrine-based Therapy Study of ... The primary endpoint of the study is Invasive breast cancer-free survival (IBCFS) and main secondary endpoints include Invasive disease-free survival (IDFS), ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04588298

NCT04588298 | A Study to Investigate the Biological ... This is a randomised, open-label, parallel-group, pre-surgical study aimed to investigate the biological effects, safety, tolerability, and pharmacokinetics ( ...

7. hemonc.org hemonc.org/w/index.php?title=Camizestrant_(AZD-9833)&mobileaction=toggle_view_desktop

Camizestrant (AZD-9833) 2 Preliminary data. 2.1 Breast cancer, HR-positive ... Upon administration, camizestrant binds to the estrogen receptor (ER) and induces a conformational change ...

8. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D8530C00003

A Study to Investigate the Biological Effects of AZD9833 in ... This is a randomised, open-label, parallel-group, pre-surgical study aimed to investigate the biological effects, safety, tolerability, and pharmacokinetics ...

9. breastcancerstudylocator.com breastcancerstudylocator.com/trial/listing/255956

Camizestrant Clinical Trial for New HER2 Negative Breast ... This clinical trial is a randomised, open-label, parallel-group, pre-surgical study aimed to investigate the biological effects, safety, ...