Afuresertib + Fulvestrant for Breast Cancer

Recruiting at 53 trial locations

Overseen By Tao Chen

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Laekna Limited

Must not be taking: Anti-epileptics, CYP3A4 substrates

Disqualifiers: Recent surgery, CNS metastases, others

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: 10

256 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs, afuresertib (an experimental treatment) and fulvestrant, to evaluate their effectiveness in treating HR+/HER2- breast cancer. The focus is on patients whose cancer has returned or spread after undergoing treatments like endocrine therapy or chemotherapy. It includes those with HR+/HER2- breast cancer that has worsened after 1 or 2 previous therapies. The aim is to determine if this combination can manage the disease more effectively than current options. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients early access to potentially effective 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, if you are taking medications that are sensitive substrates of CYP3A4, OATP1B1, or BCRP with a low therapeutic index, you may not be eligible to participate.

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

Research has shown that the combination of afuresertib and fulvestrant is generally safe. Patients in previous studies did not need to change their doses, suggesting the treatment is manageable. This combination was tested in individuals with HR+/HER2- breast cancer and was reported to be safe for them. No major unexpected medical problems were noted, indicating that the treatment is safe for humans according to current data. ^{1 2 3 4 5}

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

Unlike the standard treatments for breast cancer, which primarily include hormone therapy, chemotherapy, and targeted therapies, Afuresertib offers a novel approach by targeting a specific enzyme called AKT. This enzyme plays a crucial role in cancer cell survival and growth, making Afuresertib a promising option in stopping the cancer's progression. Researchers are excited about this treatment because it combines Afuresertib with Fulvestrant, a hormone therapy, potentially enhancing its effectiveness. This combination aims to provide a more comprehensive attack on cancer cells, possibly improving outcomes for patients who might not have responded well to other treatments.

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

This trial will evaluate the combination of afuresertib with fulvestrant for treating HR+/HER2- breast cancer. Research has shown that this combination holds promise, especially for patients who have already tried other treatments like hormone therapy or chemotherapy. Early results suggest that this treatment is both effective and safe. Participants in this trial may receive this combination, which demonstrated better outcomes in earlier studies, offering hope for those facing this type of breast cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Wenyue Ma

Principal Investigator

Laekna Limited

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

The doctor thinks you will live for at least 24 weeks.

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

My breast cancer is hormone receptor positive and HER2 negative.

Exclusion Criteria

Patients who have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation, or is not in the best interest of the participant to participate

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

Patients who are currently pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I: Safety Run-In

Safety run-in for the first 6 patients with afuresertib and fulvestrant to assess safety and tolerability

4 weeks

2 visits (in-person) on Day 1 and Day 15 of Cycle 1

Phase I: Treatment

Participants receive afuresertib and fulvestrant with monitoring for efficacy and safety

12 months

Visits every 4 weeks

Phase III: Treatment

Participants receive afuresertib or placebo combined with fulvestrant to evaluate efficacy and safety

12 months

Visits every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Afuresertib

Trial Overview 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.

How Is the Trial Designed?

Group I: Phase III: afuresertib combined with fulvestrant (experimental arm) Experimental Treatment 2 Interventions

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

Group II: Phase I: Afuresertib and Fulvestrant Safety Run In Experimental Treatment 1 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) + fulvestrant 500 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 Fulvestrant Experimental Treatment 1 Intervention

Phase I: Combination regimens are: afuresertib 125 mg QD (once daily) + fulvestrant 500 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 Group 1 Intervention

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

Who Is Running the Clinical Trial?

Laekna Limited

Lead Sponsor

Trials

8

Recruited

610+

Laekna LLC

Lead Sponsor

Trials

1

Recruited

260+

Published Research Related to This Trial

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]

In a study of 86 postmenopausal patients with ER-positive metastatic breast cancer, 500 mg of fulvestrant demonstrated a clinical benefit rate of 36.0%, indicating its efficacy in managing the disease.

Patients who had not previously undergone endocrine therapy showed significantly prolonged median progression-free survival (mPFS) of 6.5 months, suggesting that fulvestrant is particularly effective when used as a first-line treatment in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of fulvestrant in treating postmenopausal patients with estrogen receptor-positive metastatic breast cancer and prognostic analysis. Li, T., Jiao, L.[2021]

In a study of 171 postmenopausal women with estrogen receptor-positive advanced breast cancer, fulvestrant as a first-line treatment resulted in a median progression-free survival of 14.6 months, demonstrating its effectiveness in prolonging the time before cancer worsens.

The overall survival rate was 43.1 months, with a high clinical benefit rate of 82.8%, indicating that fulvestrant is not only effective but also well tolerated in real-world settings, aligning with results from randomized clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data of fulvestrant as first-line treatment of postmenopausal women with estrogen receptor-positive metastatic breast cancer. Blancas, I., Olier, C., Conde, V., et al.[2021]

In a phase II study involving 190 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, the combination of palbociclib and fulvestrant significantly improved one-year progression-free survival (PFS-1y) rates (83.5% vs. 71.9% for placebo) and median PFS (31.8 months vs. 22.0 months).

While the palbociclib/fulvestrant combination showed better efficacy, it was associated with higher rates of grade 3-4 adverse events, particularly neutropenia (68.1% vs. 0% in the placebo group), indicating a need for careful monitoring of side effects in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER). Albanell, J., Martínez, MT., Ramos, M., et al.[2022]

In a phase II study involving 87 female patients with metastatic breast cancer who had previously failed HER2-targeted therapy, afatinib alone resulted in an objective response rate of 18%.

When afatinib was combined with vinorelbine or paclitaxel for patients who progressed on afatinib monotherapy, the objective response rate increased to 31%, with manageable side effects and no significant additional toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Afatinib alone and in combination with vinorelbine or paclitaxel, in patients with HER2-positive breast cancer who failed or progressed on prior trastuzumab and/or lapatinib (LUX-Breast 2): an open-label, multicenter, phase II trial. Hickish, T., Mehta, A., Liu, MC., et al.[2022]

Fulvestrant 500 mg significantly improves the clinical benefit rate (CBR) in postmenopausal women with hormone receptor-positive advanced breast cancer compared to other endocrine therapies, based on a meta-analysis of six randomized controlled trials involving 1588 patients.

The analysis showed that fulvestrant 500 mg was particularly effective as a first-line treatment, with a notable odds ratio of 1.33 indicating a higher proportion of patients achieving a complete or partial response or stable disease for at least 24 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A meta-analysis of clinical benefit rates for fulvestrant 500 mg vs. alternative endocrine therapies for hormone receptor-positive advanced breast cancer. Robertson, JFR., Jiang, Z., Di Leo, A., et al.[2020]

Fulvestrant, an estrogen receptor antagonist, shows promising efficacy in treating metastatic ER positive and HER2 positive breast cancer, even after patients have progressed on anti-HER2 therapies, with reported response durations of up to 38 months.

The treatment is associated with limited toxicity, making it a valuable option for patients with extensive metastases, including skin and brain, highlighting the need for further research to define its role in comprehensive breast cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical benefit of fulvestrant monotherapy in the multimodal treatment of hormone receptor and HER2 positive advanced breast cancer: a case series. Rusz, O., Kószó, R., Dobi, Á., et al.[2020]

Fulvestrant is an effective estrogen antagonist for postmenopausal women with hormone-sensitive advanced breast cancer, particularly after they have progressed on other antiestrogen therapies, and it has recently been approved at a higher dose of 500 mg/month based on clinical trial results.

While fulvestrant alone is effective, combining it with growth factor signaling inhibitors may enhance its efficacy, and further research is needed to understand resistance mechanisms in patients who still respond to antiestrogen therapy after prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant in the management of postmenopausal women with advanced, endocrine-responsive breast cancer. Oakman, C., Moretti, E., Santarpia, L., et al.[2018]

In a study of 521 premenopausal and postmenopausal patients with endocrine-resistant metastatic breast cancer, those treated with palbociclib and fulvestrant showed a higher rate of prolonged benefit (29%) compared to those on placebo and fulvestrant (15%).

Long-term responders to palbociclib-fulvestrant tended to have less disease burden at baseline and lower rates of certain mutations, but no specific molecular or clinical factors were identified as predictors of long-term benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3. Cristofanilli, M., DeMichele, A., Giorgetti, C., et al.[2022]

Citations

1. laekna.com laekna.com/new/419.html

HER2- Breast Cancer at ESMO Congress 2024 LAE002 (afuresertib) has demonstrated several advantages compared to other AKT inhibitors, including higher efficacy, better potency, more ...

2. aacrjournals.org aacrjournals.org/cancerres/article/84/9_Supplement/PS17-08/744068/Abstract-PS17-08-A-Phase-Ib-Study-to-Evaluate-the

Abstract PS17-08: A Phase Ib Study to Evaluate the Efficacy ... The preliminary data from the combination therapy of afuresertib plus fulvestrant has shown promising efficacy with a well-tolerated safety profile.

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)01837-4/fulltext

370P A phase Ib study to evaluate the efficacy and safety ... The phase Ib study (NCT04851613) showed that the combination of afuresertib plus fulvestrant has promising efficacy in subjects with HR+/HER2- LA/mBC who ...

4. prnewswire.com prnewswire.com/news-releases/2023-sabcs--laekna-reports-afuresertib-phase-ib-breast-cancer-study-results-302011286.html

2023 SABCS | Laekna Reports Afuresertib Phase Ib Breast ... Investigators concluded that the combination therapy of afuresertib and fulvestrant has shown promising efficacy with a well-tolerated safety ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04851613

NCT04851613 | Study to Evaluate Efficacy & Safety of ... Study LAE205INT3101 is a Phase Ib/III study to evaluate the efficacy and safety of the combination therapy with afuresertib plus fulvestrant ...