NCT02091960

A Study to Assess the Efficacy and Safety of Enzalutamide With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2 Positive (HER2+), Androgen Receptor Positive (AR+) Metastatic or Locally Advanced Breast Cancer

Completed Phase 2 Results posted Last updated 4 April 2025

What this trial tests

Phase 2 trial testing Enzalutamide in HER2 Amplified in 103 participants. Completed in 30 January 2024.

Timeline

5 September 2014

Primary endpoint
28 February 2017

30 January 2024

Quick facts

Lead sponsor	Astellas Pharma Global Development, Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	103
Start date	5 September 2014
Primary completion	28 February 2017
Estimated completion	30 January 2024
Sites	39 locations across Italy, Belgium, United Kingdom, Canada, United States, Spain

Drugs / interventions tested

• Enzalutamide (enzalutamide) — full drug profile →
• Trastuzumab (trastuzumab) — full drug profile →

Conditions studied

• HER2 Amplified — all drugs for HER2 Amplified →
• Advanced Breast Cancer — all drugs for Advanced Breast Cancer →
• Human Epidermal Growth Factor Receptor 2 (HER2) — all drugs for Human Epidermal Growth Factor Receptor 2 (HER2) →

Sponsor

Astellas Pharma Global Development, Inc. — full company profile →

Who can join

18 and older, female only, with HER2 Amplified or Advanced Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Clinical Benefit Rate (CBR) Primary · Tumor assessments were performed every 8 weeks through week 49, and then every 12 weeks thereafter until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days.

Clinical benefit rate was defined as the percentage of evaluable participants with best objective response of confirmed complete response or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or prolonged stable disease (≥ 24 weeks). Complete response (CR) was defined as the disappearance of all target and non-target lesions and no new lesions, and lymph nodes all \< 10 mm in short axis. Partial response (PR) was defined as disappearance of target lesions or a ≥ 30% decrease in the size of target lesions, with persistence of non-target lesions and no new lesions. S

Group	Value	95% CI
Enzalutamide + Trastuzumab	23.6	15.2 – 33.8

Overall Response Rate at Week 24 Secondary · 24 weeks

Overall response rate was defined as the percentage of evaluable participants with a best objective response of confirmed complete response (CR) or partial response (PR) per RECIST 1.1. Complete response was defined as the disappearance of all target and non-target lesions and no new lesions, and lymph nodes all \< 10 mm in short axis. Partial response was defined as disappearance of target lesions or a ≥ 30% decrease in the size of target lesions with persistence of non-target lesions and no new lesions. PR and CR required confirmation with equivalent or improved assessment no less than 4 wee

Group	Value	95% CI
Enzalutamide + Trastuzumab	3.4	0.7 – 9.5

Best Overall Response Rate Secondary · Tumor assessments were performed every 8 weeks through week 49, and then every 12 weeks thereafter until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days.

Best overall response was the best response across all time points, based on investigator assessments. Best overall response rate was defined as the percentage of evaluable participants with a best objective response of confirmed complete response (CR) or partial response (PR) at any time during the study per RECIST 1.1. Complete response was defined as the disappearance of all target and non-target lesions and no new lesions, and lymph nodes all \< 10 mm in short axis. Partial response was defined as disappearance of target lesions or a ≥ 30% decrease in the size of target lesions with persis

Group	Value	95% CI
Enzalutamide + Trastuzumab	4.5	1.2 – 11.1

Progression-free Survival Secondary · From the date of first dose of study drug until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days.

Progression-free survival was defined as the time from the date of first dose of enzalutamide until the date of disease progression per RECIST 1.1, or death from any cause on study, whichever occurred first. Participants who initiated another antitumor therapy before documented progressive disease (PD) or death, or who progressed or died after missing 2 or more consecutive radiological assessments were censored at the date of the last radiological assessment showing no progression. Progressive disease was defined as a ≥ 20% increase in the size of target lesions and at least a 5 mm increase in

Group	Value	95% CI
Enzalutamide + Trastuzumab	105.0	61 – 116

Time to Progression Secondary · From the date of first dose of study drug until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days.

Time to progression was defined as the time from the first date of enzalutamide treatment until the date of disease progression per RECIST 1.1. Participants who initiated another anti-tumor therapy before documented PD, who progressed after missing two or more consecutive radiological assessments or who died before disease progression were censored at the date of the last radiological assessment showing no progression.

Group	Value	95% CI
Enzalutamide + Trastuzumab	108.0	61 – 116

Duration of Response Secondary · Tumor assessments were performed every 8 weeks through week 49, and then every 12 weeks thereafter until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days..

Duration of response was defined as the time from the date of first documentation of response (CR or PR) until the date of disease progression per RECIST 1.1. Participants who initiated another anti-tumor therapy before documented PD, progressed after missing two or more consecutive radiological assessments or who died before disease progression were censored at the date of the last radiological assessment showing no progression.

Group	Value	95% CI
Enzalutamide + Trastuzumab	NA	NA – NA

Time to Response Secondary · From the date of first dose of study drug until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days.

Time to response was defined as the time from the first date of enzalutamide treatment to initial CR or PR and was calculated for participants with a CR or PR.

Group	Value	95% CI
Enzalutamide + Trastuzumab	57	57 – 222

Number of Participants With Treatment Emergent Adverse Events (TEAEs) Secondary · From the first dose date of study drug to 30 days after the last dose date of study drug or the start of subsequent treatment or date of death, whichever was first (Up to 3031 days)

An AE was defined as any untoward medical occurrence in a participant administered study drug/who underwent study procedures and did not necessarily have a causal relationship with treatment. Abnormalities identified during medical tests were defined as an AE if they induced clinical signs/symptoms, required active intervention, interruption or discontinuation of study medication, or were clinically significant to the investigator. An AE was defined as serious if any of the following resulted: Death, was life-threatening, persistent or significant disability/incapacity or substantial disruptio

Any treatment emergent adverse events (TEAE)

Group	Value	95% CI
Enzalutamide + Trastuzumab	97

Enzalutamide Related TEAE

Group	Value	95% CI
Enzalutamide + Trastuzumab	75

Trastuzumab Related TEAE

Group	Value	95% CI
Enzalutamide + Trastuzumab	40

Any Drug Related TEAE

Group	Value	95% CI
Enzalutamide + Trastuzumab	78

Deaths

Group	Value	95% CI
Enzalutamide + Trastuzumab	4

Serious TEAE

Group	Value	95% CI
Enzalutamide + Trastuzumab	24

Enzalutamide Related Serious TEAE

Group	Value	95% CI
Enzalutamide + Trastuzumab	3

Trastuzumab Related Serious TEAE

Group	Value	95% CI
Enzalutamide + Trastuzumab	0

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose date of study drug to 30 days after the last dose date of study drug or the start of subsequent treatment or date of death, whichever is first (Up to 3031 days).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Enzalutamide + Trastuzumab

Serious: 24/103 (23%)

Deaths: 7/103

Serious adverse events (30 terms)

Reaction	System	Enzalutamide + Trastuzumab
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Nausea	Gastrointestinal disorders	—
Vomiting	Gastrointestinal disorders	—
Back pain	Musculoskeletal and connective tissue disorders	—
Abdominal pain	Gastrointestinal disorders	—
Pneumonia	Infections and infestations	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—
Diarrhoea	Gastrointestinal disorders	—
Dyspepsia	Gastrointestinal disorders	—
Asthenia	General disorders	—
General physical health deterioration	General disorders	—
Pyrexia	General disorders	—
Escherichia urinary tract infection	Infections and infestations	—
Infection	Infections and infestations	—
Accidental overdose	Injury, poisoning and procedural complications	—
Ankle fracture	Injury, poisoning and procedural complications	—
Lower limb fracture	Injury, poisoning and procedural complications	—
Post procedural haemorrhage	Injury, poisoning and procedural complications	—
Spinal compression fracture	Injury, poisoning and procedural complications	—
Brain neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Metastases to skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Myxoid liposarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Skin cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Skin neoplasm bleeding	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Hydronephrosis	Renal and urinary disorders	—

Other adverse events (25 terms — click to expand)

Reaction	System	Enzalutamide + Trastuzumab
Fatigue	General disorders	—
Nausea	Gastrointestinal disorders	—
Headache	Nervous system disorders	—
Hot flush	Vascular disorders	—
Constipation	Gastrointestinal disorders	—
Decreased appetite	Metabolism and nutrition disorders	—
Back pain	Musculoskeletal and connective tissue disorders	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—
Diarrhoea	Gastrointestinal disorders	—
Dizziness	Nervous system disorders	—
Arthralgia	Musculoskeletal and connective tissue disorders	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—
Dyspepsia	Gastrointestinal disorders	—
Vomiting	Gastrointestinal disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Anaemia	Blood and lymphatic system disorders	—
Anxiety	Psychiatric disorders	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—
Restless legs syndrome	Nervous system disorders	—
Hypertension	Vascular disorders	—
Asthenia	General disorders	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—
Neck pain	Musculoskeletal and connective tissue disorders	—
Pruritus	Skin and subcutaneous tissue disorders	—

Most-reported serious reactions: Malignant neoplasm progression, Nausea, Vomiting, Back pain, Abdominal pain, Pneumonia, Dyspnoea, Diarrhoea.

Data from ClinicalTrials.gov NCT02091960 adverse events section.

Sponsor's own description

The purpose of this study was to evaluate the efficacy of enzalutamide with trastuzumab in patients with HER2+ AR+ metastatic or locally advanced breast cancer.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Androgen Receptor in Breast Cancer-Clinical and Preclinical Research Insights.
   Anestis A, Zoi I, Papavassiliou AG, Karamouzis MV. · · 2020 · cited 110× · PMID 31952272 · DOI 10.3390/molecules25020358
2. AR Signaling in Breast Cancer.
   Rahim B, O'Regan R. · · 2017 · cited 83× · PMID 28245550 · DOI 10.3390/cancers9030021
3. ARe we there yet? Understanding androgen receptor signaling in breast cancer.
   Michmerhuizen AR, Spratt DE, Pierce LJ, Speers CW. · · 2020 · cited 82× · PMID 33062889 · DOI 10.1038/s41523-020-00190-9
4. Expression of androgen receptor splice variants in clinical breast cancers.
   Hickey TE, Irvine CM, Dvinge H, Tarulli GA, et al · · 2015 · cited 77× · PMID 26554309 · DOI 10.18632/oncotarget.6296
5. Targeting the androgen receptor in prostate and breast cancer: several new agents in development.
   Proverbs-Singh T, Feldman JL, Morris MJ, Autio KA, et al · · 2015 · cited 69× · PMID 25722318 · DOI 10.1530/erc-14-0543
6. Androgen receptor function and targeted therapeutics across breast cancer subtypes.
   Kolyvas EA, Caldas C, Kelly K, Ahmad SS. · · 2022 · cited 59× · PMID 36376977 · DOI 10.1186/s13058-022-01574-4
7. Targeting Breast Cancer: An Overlook on Current Strategies.
   Iacopetta D, Ceramella J, Baldino N, Sinicropi MS, et al · · 2023 · cited 57× · PMID 36835056 · DOI 10.3390/ijms24043643
8. Emerging therapeutic targets in metastatic progression: A focus on breast cancer.
   Li Z, Kang Y. · · 2016 · cited 51× · PMID 27000769 · DOI 10.1016/j.pharmthera.2016.03.003