What side effects are associated with this type of intervention?

Common side effects of breast cancer treatments similar to Afuresertib and Fulvestrant include hyperglycemia, diarrhea, rash, and fatigue from AKT inhibitors, and injection site pain, nausea, fatigue, and hot flashes from estrogen receptor antagonists. Combining these treatments may lead to overlapping toxicities like fatigue and gastrointestinal issues.

What prior FDA approvals exist?

The FDA has approved several treatments for hormone receptor-positive, HER2-negative breast cancer that combine targeted agents with endocrine therapy. Notably, the combination of CDK4/6 inhibitors (such as palbociclib, ribociclib, and abemaciclib) with endocrine therapies like letrozole or fulvestrant has been approved, showing significant improvements in progression-free survival. Additionally, the PI3K inhibitor alpelisib in combination with fulvestrant has been approved for patients with PIK3CA-mutated breast cancer. These approvals highlight the efficacy of combining targeted therapies with endocrine agents in treating advanced breast cancer.

What other types of research exist?

Promising alternatives to Afuresertib plus Fulvestrant for breast cancer patients include: 1) Palbociclib plus Fulvestrant, which has shown significant prolongation in PFS in the PALOMA-3 trial. 2) Everolimus plus Exemestane, which has demonstrated efficacy in hormone receptor-positive, HER2-negative disease. 3) Lenvatinib plus Pembrolizumab, which has shown improved PFS and OS in various cancers and may be considered for breast cancer treatment pending further studies.

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Protein Kinase Inhibitor

Afuresertib + Fulvestrant for Breast Cancer

Phase 3

Recruiting

Research Sponsored by Laekna Limited

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients with histologically or cytologically confirmed HR+/HER2- BC characterized by the absence of HER2 expression and the presence of ER and/or PR expression

Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1

Must not have

Patients who have a history of seizure or conditions that may predispose them to seizure and require anti-epileptic medications, or patients who have brain arteriovenous malformation, or intracranial masses

Patients who have Child-Pugh status of B and C

Timeline

Screening 3 weeks

Treatment Varies

Follow Up phase i: through study completion for an average of 12 months

Awards & highlights

Pivotal Trial

Summary

This trial tests a combination of two drugs, afuresertib and fulvestrant, for patients with a specific type of breast cancer who haven't responded to other treatments. The drugs work together to block cancer cell growth by targeting different pathways. Fulvestrant is an effective drug used for treating hormone receptor-positive, HER2-negative advanced breast cancer, often in combination with other targeted therapies.

Who is the study for?

This trial is for adults with HR+/HER2- advanced or metastatic breast cancer who've had certain prior treatments. Participants must be post-menopausal or on ovarian suppression therapy, have a good performance status and life expectancy, and agree to use contraception. They can't join if they have heart issues, seizures, other serious health conditions, are pregnant/breastfeeding, or have used specific drugs recently.

What is being tested?

The study tests the combination of afuresertib plus fulvestrant in patients whose breast cancer hasn't responded well to previous therapies. It's designed to see if this combo is effective and safe compared to standard treatments.

What are the potential side effects?

While not specified here, common side effects may include reactions at the injection site from fulvestrant, gastrointestinal issues from oral medications like afuresertib, fatigue, possible liver function changes and potential hormonal imbalances.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My breast cancer is positive for hormone receptors and negative for HER2.

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I am fully active or can carry out light work.

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My blood, kidney, liver, clotting ability, and sugar levels are all within normal ranges.

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I can swallow pills and don't have stomach issues affecting medication absorption.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of seizures or conditions that may lead to seizures, or I have brain arteriovenous malformation or intracranial masses.

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My liver disease is moderately to severely advanced.

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I am a woman who can have children and my pregnancy test before the study was positive.

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I haven't had serious heart problems or blood clots in the last 6 months.

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I am currently taking medication that strongly affects liver enzymes.

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I have an active Hepatitis B or C infection.

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My high blood pressure is not under control.

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I have previously been treated with medications targeting estrogen receptors or specific cancer growth pathways.

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I have active brain metastases or carcinomatous meningitis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ phase i: through study completion for an average of 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~phase i: through study completion for an average of 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and phase i: through study completion for an average of 12 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase I: Overall Response Rate (ORR) based on RECIST 1.1

Phase III: Progression Free Survival (PFS) based on RECIST 1.1, as assessed by investigators

Secondary study objectives

Phase I: Best Overall Response (BOR) based on RECIST 1.1

Phase I: Disease Control Rate (DCR) based on RECIST 1.1

Phase I: Duration of Response (DOR) based on RECIST 1.1

+8 more

Side effects data

From 2021 Phase 3 trial • 693 Patients • NCT02028507

73%

Palmar-plantar erythrodysesthesia syndrome

58%

Fatigue

56%

Diarrhea

38%

Hypertension

38%

Nausea

30%

Mucositis

29%

Vomiting

26%

Weight loss

26%

Weight gain

24%

Anorexia

20%

Nail disorder

17%

Back pain

16%

Hypothermia

15%

Constipation

15%

Abdominal pain

14%

Neutrophil count decreased

13%

Dizziness

13%

Upper respiratory infection

13%

Headache

11%

Dyspepsia

10%

Pain in extremity

10%

Fever

10%

Obesity

10%

Dysgeusia

Bone pain

Anemia

Arthralgia

Cough

Pruritus

Flu like symptoms

Pain

Alopecia

Thromboembolic event

Bone fracture

Gastrointestinal infection

Spinal cord compression

Febrile neutropenia

Respiratory infection

Hot flashes

Pancreatitis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1 and 2: Capecitabine

Cohort 1: Palbociclib Plus Exemestane

Cohort 2: Palbociclib Plus Fulvestrant

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: Phase III: afuresertib combined with fulvestrant (experimental arm)Experimental Treatment1 Intervention

Phase III: afuresertib 125mg QD combined with fulvestrant 500mg Q4W (D1, 15 in cycle 1)

Group II: Phase I: Afuresertib and Fulvestrant Safety Run InExperimental Treatment1 Intervention

Phase I: Safety run-in Cycle 1 (a cycle is 28 days) will be performed in the first 6 patients of the phase Ib. Combination regimens during the safety run-in period are: afuresertib 125 mg QD (once daily) or 125 mg Day1-21 Q4W + fulvestrant 500 mg or 250 mg Intra Muscular (IM) on Day 1, 15 of Cycle 1, and on Day 1 of the subsequent 28-day cycles.

Group III: Phase I: Afuresertib and FulvestrantExperimental Treatment1 Intervention

Phase I: Combination regimens are: afuresertib 125 mg QD (once daily) or 125 mg Day1-21 Q4W + fulvestrant 500 mg or 250 mg Intra Muscular (IM) on Day 1, 15 of Cycle 1, and on Day 1 of the subsequent 28-day cycles.

Group IV: Phase III:placebo combined with fulvestrant (control arm)Placebo Group1 Intervention

PhaseIII：placebo combined with fulvestrant 500mg Q4W (D1, 15 in cycle 1)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Afuresertib

2020

Completed Phase 2

~180

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Breast cancer treatments often target specific pathways involved in cancer cell growth and survival. AKT inhibitors, like Afuresertib, block the AKT signaling pathway, which is crucial for cell proliferation and survival, thereby inducing cancer cell death. Estrogen receptor antagonists, such as Fulvestrant, bind to estrogen receptors on cancer cells, blocking estrogen from stimulating cancer growth. This is particularly important for hormone receptor-positive breast cancers. Other common treatments include aromatase inhibitors, which reduce estrogen production, and HER2 inhibitors, which target the HER2 protein overexpressed in some breast cancers. Understanding these mechanisms helps tailor treatments to the specific characteristics of a patient's cancer, potentially improving outcomes and minimizing side effects.

Abemaciclib plus fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in premenopausal women: subgroup analysis from the MONARCH 2 trial.An Experimental Analysis of the Molecular Effects of Trastuzumab (Herceptin) and Fulvestrant (Falsodex), as Single Agents or in Combination, on Human HR+/HER2+ Breast Cancer Cell Lines and Mouse Tumor Xenografts.A Phase I Trial of BKM120 (Buparlisib) in Combination with Fulvestrant in Postmenopausal Women with Estrogen Receptor-Positive Metastatic Breast Cancer.