New combo targets Hard-to-Treat breast cancer

NCT ID NCT04851613

Disease control Sponsor: Laekna Limited Source: ClinicalTrials.gov ↗

First seen Jun 26, 2026 · Last updated Jun 27, 2026 · Updated 1 time

Summary

This phase 3 trial tests whether adding afuresertib (a targeted drug) to fulvestrant (a standard hormone therapy) can help control advanced HR+/HER2- breast cancer that has stopped responding to other treatments. The study includes 256 adults with specific genetic changes (PIK3CA/AKT1/PTEN). The goal is to slow cancer growth, not to cure it.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: afuresertib (a targeted drug) plus fulvestrant (a hormone therapy)
What this could lead to: If successful, this combination could offer a new treatment option for people with a specific genetic subtype of advanced breast cancer that has stopped responding to standard therapies.
What could go wrong: This is a late-stage trial, but the benefit is limited to patients with certain genetic changes (PIK3CA/AKT1/PTEN). The drug may cause side effects, and it is not a cure—disease control is the goal.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 3

Large-scale testing in a bigger group. Usually the last step before a treatment can be approved.

Participants

About 256 people

The number the study aims to enrol. It can still change while the study runs.

Started

Feb 2022

Expected to finish

Dec 2026

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Female or male patients must be ≥ 18 years of age on the day of signing the informed consent and be able to provide written informed consent for the study. 2. Patients with histologically or cytologically confirmed HR+/HER2- Breast Cancer characterized by the absence of HER2 expression and the presence of ER with/without PR expression. 3. Female patients may be post-menopausal, pre-menopausal or peri-menopausal. Male and Pre- and peri-menopausal females may be enrolled if continuously treated with ovarian suppression therapy (use LHRHa at least starting from C1D1) for the duration of study participation. 4. Before enrollment, patients who have undergone anti-cancer treatment must have a washout period of 4 weeks or 5 half-lives, whichever comes earlier. 5. HR+/HER2- BC patients must meet all the following criteria to join this study: 1. Relapsed locally advanced (LABC) or metastatic (mBC) disease; AND 2. Have received 1 to 2 prior lines of systemic treatments for LABC or mBC(at least one line was ET). If disease relapse during adjuvant therapy or relapse within 12 months from completion of adjuvant endocrine therapy, the adjuvant therapy will be counted as 1 line), including: i. Endocrine therapies including AIs and/or SERMs (1 or 2 lines) with or without a CDK4/6 inhibitor (up to 1 therapy); OR ii. A chemotherapy (monotherapy or combination therapy, at most 1 line only), with 1 additional line of endocrine therapy . 6. For phase Ib part, patients must have at least one lesion that meets the definition of measurable disease by RECIST 1.1 criteria; for phase III, have measurable disease and/or at least 1 lytic or mixed (lytic + sclerotic) bone lesion that can be assessed by RECIST 1.1 criteria; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible (Appendix 2). 7. In the Phase Ib part, Patients must provide informed consent for the procedures and the tests for PIK3CA/AKT/PTEN alterations and ESR1 mutations. The biomarkers will be tested retrospectively by gene sequencing tests using archival tumor sample (preferably within 18 months/78 weeks) or from peripheral blood or from a tumor biopsy sample. Formalin-fixed, paraffin embedded (FFPE) tissue blocksare preferred. In phase III, blood sample is mandatory for this test. 8. In Phase III, subjects need to provide blood sample during the screening period for PIK3CA/AKT1/PTEN test, which will be conducted in the central laboratory. Only patients with PIK3CA/AKT1/PTEN alterations could include. 9. Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1. 10. Patients who have adequate organ function as defined. 11. Patients without a pre-existing diagnosis of diabetes mellitus (DM) who have a fasting glucose ≤ 126 mg/dL (or ≤ 7.0 mmol/L); or patients with type 2 diabetes who have a fasting glucose ≤ 167 mg/dL (or ≤ 9.3 mmol/L) AND glycosylated hemoglobin (HbA1c) ≤ 8%. Patients with DM type 1 or patients with DM type 2 requiring insulin or ≥21 anti-abetic medications for glycemic control are excluded. 12. Patients with a life expectancy of 24 weeks or more based on investigator's assessment. 13. Patients who have recovered from adverse events associated with pre-study medical, radiation and surgical treatments to ≤ Grade 1, excluding stable symptoms (e.g., alopecia, peripheral sensory neuropathy, skin hyperpigmentation, dysgeusia, etc.). 14. Female patients of childbearing potential must have a negative pretreatment serum pregnancy test. 15. Female patients of childbearing potential must agree to use effective contraception from enrollment to 1 year after discontinuation from the last dose of this study treatment. 16. Patients who are able to swallow and retain oral medication and without gastrointestinal diseases to interfere with drug absorption. 17. Patients must have no contraindications to fulvestrant. Exclusion Criteria: 1. Patients who had a recent major surgery that required hospitalization for longer than 48 hours (\< 8 weeks from scheduled treatment starting date) or have used IV antibiotics for the treatment of systemic infection (\< 2 weeks from scheduled treatment starting date). 2. Patients who have additional known malignancies that are progressing or have required active treatments within 3 years of scheduled treatment starting date. (Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, that have undergone potentially curative therapy are not excluded). 3. 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 that are causing edema or clinical symptoms. 4. Patients who have known active CNS metastases and/or carcinomatous meningitis. (Note: Patients with previously treated brain metastases may participate provided that they are radiologically stable (i.e., without evidence of progression for at least 4 weeks by repeated imaging performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to schedule treatment starting date. 5. Patients who had prior treatment with fulvestrant or other selective estrogen receptor degraders (SERDs), or any PI3K/AKT/mTOR inhibitors, or any CDK4/6 inhibitors in phase I, II study. 6. Patients who had the following conditions within 6 months (26 weeks) of scheduled treatment starting date: New York Heart Association congestive heart failure classification III to IV, unstable angina, myocardial infarction, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or serious cardiac arrhythmia associated with significant cardiovascular impairment as determined by the investigator. 7. Patients with QT interval corrected by the Frederica's correction formula (QTcF) \> 470 msec(average value), unless the prolonged QT interval is due to (right or left) bundle branch block and/or pacemaker rhythm. If wide QRS complex is present, cardiology consultation is required to assess the risk for Torsade de Pointes. Note: QTcF = QT/(RR\^0.33) . 8. Patients who have uncontrolled hypertension (systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg under anti-hypertensive treatment). Note: Patients with a history of hypertension are allowed, provided that blood pressure is controlled to within these limits by anti-hypertensive treatment. 9. Patients with active Hepatitis B infection \[defined as HBsAg (+) and HBV-DNA ≥ 200 IU/ml (1000 copy/ml)\] or active Hepatitis C virus \[defined as HCV antibody positive and HCV RNA (qualitative) test positive\]. 10. Patients with known HIV seropositivity who has 1 of the following: 1. Not receiving highly active antiretroviral therapy 2. Receiving antiretroviral therapy that may interfere with the study drug (consult the Sponsor/Medical Monitor for review of medication prior to enrollment) 3. CD4 count \< 350 based on a test within 3 months of the screening visit 4. An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months (26 weeks) of the start of study screening 11. Patients who have a history or current evidence of any condition, therapy, or laboratory abnormality that in the opinion of the investigator, might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate. 12. Patients who have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study. 13. Patients who are receiving medications that are sensitive substrates of CYP3A4, OATP1B1, or BCRP with low therapeutic index. Please see related section for a list of these prohibited medications. 14. Patients who are currently pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 1 year after the last dose of study treatment. 15. Patients who have known cirrhosis with a Child-Pugh status of B and C. 16. Patients who are ineligible for endocrine therapy (e.g., visceral crisis, inflammatory breast cancer, uncontrolled pleural or abdominal fluid drainage ≥4 times within one month before planned administration).

Get updates

Get notified about this study

Vår säkerhetsrekommendation!

Genom att skicka in godkänner du våra Användarvillkor

Conditions

The condition(s) this trial relates to.

breast cancer breast neoplasm hormone receptor-positive breast cancer

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Breast cancer

Contacts and locations

Locations

Affiliated Hospital of Hebei University

Baoding, Hebei, 071000, China
Affiliated Hospital of Nantong University

Nantong, Jiangsu, China
Anhui Provincial Cancer Hospital

Hefei, Anhui, 230031, China
Anyang cancer hospital

Anyang, Henan, 455000, China
Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China
Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China
Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, 400030, China
Fujian Cancer Hospital

Fuzhou, Fujian, 350014, China
Guangxi Zhuang Autonomous Region People's Hospital

Nanning, Guangxi, 530021, China
Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150081, China
Henan Cancer Hospital

Zhengzhou, Henan, 450008, China
Hubei Cancer Hospital

Wuhan, Hubei, 430079, China
Hunan Cancer Hospital

Changsha, Hunan, 410013, China
Jiangsu Cancer Hospital

Nanjing, Jiangsu, 210009, China
Jiangsu Provincial People's Hospital

Nanjing, Jiangsu, 210029, China
Jilin Provincial Cancer Hospital

Changchun, Jilin, 130012, China
Liaoning Cancer Hospital

Shenyang, Liaoning, 110000, China
Ningbo Li Huili Hospital

Ningbo, Zhejiang, 315040, China
Northern Jiangsu People's Hospital

Yangzhou, Jiangsu, 225001, China
Peking Union Medical College Hospital (PUMCH)

Beijing, Beijing Municipality, 100730, China
Piedmont Cancer Institute

Atlanta, Georgia, 30318, United States
Providence St. Johns Health Center

Santa Monica, California, 90404, United States
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200020, China
Shandong Cancer Hospital

Jinan, Shandong, 250117, China
Shengjing Hospital of China Medical University

Shenyang, Liaoning, 110004, China
Sichuan Cancer Hospital

Chengdu, Sichuan, 610041, China
Sichuan Provincial People's Hospital

Chengdu, Sichuan, 610072, China
Sir-run shaw Hospital Zhejiang University of Medicine

Hangzhou, Zhejiang, 310016, China
Sun Yat-sen Memorial Hospital，Sun Yat-sen University

Guangzhou, Guangdong, 510000, China
Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510050, China
Taizhou Hospital

Taizhou, Zhejiang, 317000, China
Tangshan People's Hospital

Tangshan, Hebei, 063000, China
The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, 233004, China
The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400016, China
The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, 530021, China
The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China
The First Affiliated Hospital of Xi'an Jiaotong University

Xi’an, Shanxi, 710061, China
The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China
The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China
The First Hospital of China Medical University

Shenyang, Liaoning, 110001, China
The First People's Hospital of Foshan

Foshan, Guangdong, 528000, China
The Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050011, China
The first hospital of Jilin University

Changchun, Jilin, 130000, China
Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 300060, China
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China
Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China
University of Iowa

Iowa City, Iowa, 52242, United States
University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States
University of Vermont

Burlington, Vermont, 05401, United States
Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States
West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China
Wuhan Central Hospital

Wuhan, Hubei, 430022, China
Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China
Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China
Zhongshan People's Hospital

Zhongshan, Guangdong, 528403, China

More trials for these conditions

Other studies related to the condition(s) this trial covers.