Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Breast Neoplasms

Breast Neoplasms, Male

Breast Diseases

Skin Diseases

Breast Cancer, Male

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Tamoxifen

Hormones

Anastrozole

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Antineoplastic Agents, Hormonal

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

Aromatase Inhibitors

Enzyme Inhibitors

Participants will be randomly assigned to receive Tamoxifen 1x daily for 3 weeks (21days).

Participants will be randomly assigned to receive Anastrozole 1x daily for 3 weeks (21days).

Participants will be randomly assigned to receive Anastrozole 1x daily for 3 weeks (21days) and Degarelix on day 1 only.

Participants will be randomly assigned to receive Tamoxifen 1x daily for 4 cycles (4 months); each study cycle is 28 days.

Participants will be randomly assigned to receive Tamoxifen 1x daily and Abemaciclib 2x daily for 4 cycles (4 months); each study cycle is 28 days.

Participants will be randomly assigned to receive Anastrozole 1x daily and Degarelix on day 1 of each cycle for 4 cycles (4 months); each study cycle is 28 days.

Participants will be randomly assigned to receive Anastrozole 1x daily, Degarelix on day 1 of each cycle and Abemaciclib 2x daily for 4 cycles (4 months); each study cycle is 28 days.

Degarelix

Abemaciclib

Jose Pablo Leone, MD

Clinical Trials Office Breast Cancer

Elaine Walsh, MD

Cancer Trials Referral Office

Kathryn Ruddy, MD

Clinical Trials Office - M. D. Anderson Cancer Center at the U

Jasmine Sukumar, M.D

This research study is looking to see how well male breast cancer responds to preoperative treatment with endocrine therapy and which endocrine therapy regimen is the most effective treatment for male breast cancer.

The drugs used in this study are:

* Tamoxifen
* Anastrozole
* Degarelix
* Abemaciclib

This is an open-label, multicenter, randomized trial for men with stage I-III hormone receptor-positive (HR+)/HER2-negative breast cancer. The trial will have two phases: A 3-week window phase containing endocrine therapy followed by a 4-month treatment phase where participants are treated with one of four endocrine therapy treatment combinations.

Tamoxifen is the standard of care for the treatment of breast cancer in men. Anastrozole is a standard treatment in women with breast cancer and works more effectively than tamoxifen. This study hopes to learn if anastrozole may also be effective in men. Given that gonadal suppression and CDK 4/6 inhibitors have both improved treatment in women with breast cancer, the study hopes to learn how the addition of Degarelix (gonadal suppression) and Abemaciclib (CDK 4/6 inhibitors) work in comparison to standard of care tamoxifen.

The research study procedures include screening for eligibility and study treatment including laboratory evaluations and quality of life questionnaires.

After completion of treatment, participants will be followed for up to 10 years

It is expected that about 60 men will take part in this research study.

Eli Lilly, a pharmaceutical company, is supporting this research study by providing one of the study drugs. This study is also being supported by Johns Hopkins University on behalf of the Translational Breast Cancer Research Consortium (TBCRC).

ETHAN - ET for Male BC

ETHAN: A Phase II Study Comparing Different Endocrine THerapies for mAle Breast caNcer

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

All grade 3 or higher adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms were counted. Rate is the proportion of treated participants experiencing at least one treatment-related grade 3 or higher AE of any type during the time of observation.

We will evaluate how many patients we are able to enroll to this trial in a period of 3 years

We will evaluate how many of the enrolled participants successfully complete the study protocol

Patient-reported outcomes (PROs) measures will be conducted using the EORTC QLC-C30 questionnaire.

Patient-reported outcomes (PROs) measures will be conducted using the EORTC BR23, adapted by replacing female-specific items with male-specific sexual activity/function items from PR25 (Appendix D of protocol) questionnaire.

Ki-67 will be evaluated by ImmunoHistoChemistry (IHC) following consensus recommendations using imaging analysis methods.

RCB will be determined using data from each participating institution pathology department, and will be reviewed by the study team pathologist.

To evaluate the physiologic endocrine changes that occur as a result of treatment with tamoxifen, anastrozole and anastrozole and degarelix as measured by estradiol levels at baseline and at the end of the three-week window period

To evaluate the physiologic endocrine changes that occur as a result of treatment with tamoxifen, anastrozole and anastrozole and degarelix as measured by testosterone levels at baseline and at the end of the three-week window period

To evaluate the comparative efficacy of the experimental treatments as measured by PEPI score at surgery.

Eli Lilly and Company

Translational Breast Cancer Research Consortium (TBCRC)

Jose Pablo Leone

Principal Investigator

Triple Negative Breast Neoplasms

Anti-Infective Agents

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Hematinics

Ado-Trastuzumab Emtansine

Trastuzumab

Vaccines

Metronidazole

Immunomodulating Agents

Mitogens

Progesterone

Adenosine

Iron-Dextran Complex

Entinostat

Maytansine

Antineoplastic Agents, Immunological

Tubulin Modulators

Antimitotic Agents

Immunotoxins

Immunoconjugates

Immunologic Factors

Histone Deacetylase Inhibitors

Arm 1 - Triple Negative Breast Cancer.

Bifunctional fusion molecule involving programmed death-ligand 1 (PD-L1) with transforming growth factor beta (TGF-b) sequestering agent added to a vaccine for the tumor associated antigen called brachyury.

Arm 2 - Estrogen receptor (ER)-/progesterone receptor (PR)-/Human Epidermal Growth Factor Receptor 2 (HER2) + Breast Cancer.

Bifunctional fusion molecule involving programmed death-ligand 1 (PD-L1) with transforming growth factor beta (TGF-b) sequestering agent added to a vaccine for the tumor associated antigen called brachyury. These investigational agents will be added to standard of care treatment called Ado-trastuzumab emtansine (T-DM1).

Estrogen receptor (ER)-/progesterone receptor (PR)-/Human Epidermal Growth Factor Receptor 2 (HER2)+ Breast Cancer.

Bifunctional fusion molecule involving programmed death-ligand 1 (PD-L1) with transforming growth factor beta (TGF-b) sequestering agent added to a vaccine for the tumor associated antigen called brachyury as well as to an oral histone deacetylase (HDAC) inhibitor called entinostat. These investigational agents will be added to standard of care treatment called Ado-trastuzumab emtansine (T-DM1). (T-DM1).

Every three weeks, until cycle 9, then every 12 weeks: \*Recombinant MVA-Bavarian Nordic (BN)-Brachyury recommended phase 2 dose (R2PD): 4 injections of vaccines with 1 given subcutaneous (SC) in each extremity on Day 1 of Cycles 1 and 2. Each injection of MVA-BN-Brachyury consists of 2.0 x 10\^8 infectious units (Inf.U). \*Recombinant fowlpox virus (FPV)-BN-Brachyury: 1 injection given SC in one extremity on Day 1 of Cycles 3 and beyond. Each injection of FPV-BN-Brachyury consists of 1.0 x 10\^9 Inf.U.

Brachyury-TRICOM

5mg by mouth weekly (RP2D) administered by patient on Days 1, 8 and 15 of each cycle.

1800mg via intravenous (IV) infusion every (q)3 weeks on Day 1 of each cycle.

M7824

3.6mg/kg via intravenous (IV) infusion every (q)3 weeks on Day 1 of each cycle.

Ado-trastuzumab emtansine

Fatima H Karzai, M.D.

Background:

Breast cancer is the second most common cause of United States (U.S.) cancer deaths in women. Immunotherapy drugs use a person's immune system to fight cancer. Researchers want to see if a new combination of immunotherapy drugs can help treat breast cancer that has gone to places in the body outside of the breast (metastasized).

Objective:

To learn if a new combination of immunotherapy drugs can shrink tumors in people with metastatic breast cancer.

Eligibility:

Adults 18 and older who have been diagnosed with metastatic breast cancer, such as Triple Negative Breast Cancer (TNBC) or estrogen receptors (ER)-/progesterone receptors (PR)-/human epidermal growth factor receptor 2 (HER2)+ Breast Cancer (HER2+BC)

Design:

Participants will be screened with:

medical history

physical exam

disease confirmation (or tumor biopsy)

tumor scans (computed tomography, magnetic resonance imaging, and/or bone scan)

blood and urine tests

electrocardiogram (measures the hearts electrical activity)

echocardiogram (creates images of the heart).

Participants will be assigned to 1 of 3 groups. The drugs they get will be based on the group they are in. Drugs are given in cycles. Each cycle = 3 weeks. Participants will be seen in clinic every 3 weeks, prior to the start of a new cycle. At each visit, participants will have an clinical exam, have blood drawn and will be asked about any side effects. They will repeat the screening tests during the study. New scans, like a computed tomography (CT) scan, will be done every 6 weeks to see if the treatment is working.

All participants will get Bavarian Nordic (BN)-Brachyury. It is 2 different vaccines - a prime and a boost. First the priming vaccines, called MVA-BN-Brachyury help to jump start the immune system. Next the boosting vaccines, called fowlpox virus (FPV)-Brachyury help to keep the immune system going. They are injected under the skin during different cycles.

All participants will get M7824 (also known as Bintrafusp alfa), which is an immunotherapy drug. Some participants will get a commonly used drug is HER2+ breast cancer called adotrastuzumab emtansine (also known as T-DM1DM1 or kadcyla). For both, a needle is inserted into a vein to give the drugs slowly.

Some participants will take Entinostat weekly by mouth. It is in tablet form. Participants will keep a pill diary.

Participants will continue on their assigned treatment until their cancer grows, they develop side effects or want to stop treatment. About 28 days after treatment ends, participants will have a follow-up visit or a telephone call. Then they will be contacted every 3 months for 1 year, then every 6 months for 1 year. They may have more tumor scans or continue treatment.

Background:

* Current greater than or equal to 2nd line treatments for metastatic breast cancer provide modest response rates, and modest improvement in progression-free survival but no treatments are curative.
* Bavarian-Nordic (BN)-Brachyury vaccine is a recombinant poxvirus vaccine against the transcription factor brachyury, which plays an important role in the epithelial-to-mesenchymal transition in breast cancer. A recently completed phase 1 study of BN-Brachyury vaccine showed the vaccine was well tolerated and generated an immune response.
* M7824 (Bintrafusp alfa) is a novel bifunctional fusion protein composed of a monoclonal antibody against human programmed death-ligand 1 (PD-L1) fused to the soluble extracellular domain of human transforming growth factor (TGF)-Beta receptor II (TGF-BetaRII(241-R2), which functions as a TGF-Beta trap.
* Ado-trastuzumab emtansine (T-DM1 or Kadcyla) is an antibody drug conjugate used in second- and third- line treatment of metastatic human epidermal growth factor receptor 2 (HER2+) breast cancer (HER2+BC). T-DM1 activates antibody-dependent cellular cytotoxicity (ADCC), dendritic cell maturation, increases tumor infiltrating lymphocytes (TILs), increased PD-L1 expression, and increased immunomodulatory cytokines.
* Entinostat is a class 1 histone deacetylase inhibitor (HDACi) which suppresses tumor initiating cells, regulatory T-cells and myeloid-derived suppressor cells (MDSCs), as well as enhances cytotoxic T-cell mediated lysis, direct natural killer (NK) lysis, NK cell activation, increases PD-L1 expression and antibody-dependent cellular cytotoxicity (ADCC). In addition, entinostat may also be able to overcome HER2 resistance.
* We propose a Phase 1b trial to evaluate the safety and efficacy of the stepwise combination of the BN-Brachyury vaccine, M7824, T-DM1 and entinostat in metastatic breast cancer.

  * Arm 1 - Triple Negative Breast Cancer (TNBC); M7824 + BN-Brachyury
  * Arm 2 - estrogen receptors (ER)-/progesterone receptors (PR-)/HER2+ Breast Cancer; M7824 + BN-Brachyury + T-DM1
  * Arm 3 - ER-/PR-/HER2+ Breast Cancer; M7824 + BN-Brachyury + T-DM1+ Entinostat

Objectives:

Primary Objectives:

* Arms 1-3: Overall response rate (overall response rate (ORR); partial response (PR)+complete response (CR)
* Arms 1-3: Safety for each of the three combinations of agents explored in the arms

Eligibility:

Selected Inclusion Criteria

* Histologically confirmed metastatic breast cancer with appropriate immunohistochemistry (IHC) testing by a certified lab:

  * For Arm 1: Triple negative breast cancer. Hormone receptor negative is defined by estrogen receptor \< 10% and progesterone receptor \< 10%. HER2 negative breast cancer is defined as HER2 per IHC 0 or 1+ or 2+ with negative fluorescence in situ hybridization (FISH).
  * For Arms 2 and 3: Hormone receptor negative, HER2+ breast cancer as defined by estrogen receptor \< 10% and progesterone receptor \< 10%. HER2 positive as per IHC 3+ or 2+ with positive FISH.
* Prior treatment:

  * For Arm 1: greater than or equal to 1 prior therapy in the metastatic setting. Patients with known PD-L1 positive tumors must have received prior treatment with atezolizumab + nab-paclitaxel. Patients with ER 1-9% must have received treatment with at least two lines of endocrine treatment (selective estrogen receptor modulators (SERM), AI, fulvestrant) with one prior treatment including a cyclin-dependent kinase 4 (CDK4)/6 inhibitor + endocrine therapy for their metastatic cancer and should be considered endocrine therapy resistant.
  * For Arms 2 and 3: greater than or equal to 1 prior treatment in the metastatic setting with a taxane (docetaxel or paclitaxel), herceptin and pertuzumab.
* Females or males greater than or equal to 18 years old
* Eastern Cooperative Oncology Group (ECOG) 0 or 1
* Measurable metastatic disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
* For Cohort 3, Arms 2 and 3: At least one biopsiable lesion and willingness to undergo up to three research biopsies.
* Adequate hematopoietic, hepatic, renal and cardiac (ejection fraction (EF) greater than or equal to 50%) function.

Selected Exclusion Criteria

* Patients who have received chemotherapy, including trastuzumab and pertuzumab in the previous 3 weeks; other investigational agents within 4 weeks or a programmed cell death protein 1 (PD-1)/PD-L1 antibody within 4 weeks prior to study enrollment; radiotherapy less than or equal to 4 weeks of study entry.
* Symptomatic central nervous system (CNS) metastases and leptomeningeal disease are excluded but treated brain metastases (no radiotherapy within 6 weeks) or asymptomatic brain metastasis are allowed.
* History of invasive malignancy less than or equal to 3 years prior to enrollment.
* History of congestive heart failure (CHF) as defined as New York Heart Association (NYHA) class 3 or 4 or hospitalization for CHF (any NYHA class) within 6 months of trial start.
* Concurrent use of chronic systemic steroids except for physiologic systemic steroids for replacement defined as 10mg of prednisone or an equivalent dose.

Design:

This study contains three separate, single arm phase 1b trials.

* Arm 1 will evaluate M7824 and BN-Brachyury in patients with triple-negative breast cancer (TNBC).
* If this doublet is determined to have acceptable toxicity (0-1 dose limiting toxicities (DLTs) of the first 6 patients), up to 19 patients will be enrolled on Arm 2 in which BN-Brachyury, M7824 and T-DM1 will be evaluated in patients with advanced HR-/HER2+ BC with disease progression after treatment with docetaxel (THP) or intolerance to THP.
* If this triplet is determined to have acceptable toxicity (0-1 DLTs of the first 6 patients), 19 patients will be enrolled on Arm 3 in which BN-Brachyury, entinostat, M7824 and T-DM1 will be evaluated in patients with advanced HR-/HER2+ BC with disease progression after treatment with THP or intolerance to THP.
* Up to 51 evaluable patients will be recruited for this study, with an accrual ceiling set at 65 patients.

Trial Drugs

* BN-Brachyury vaccine every 3 weeks until cycle 9, then every 12 weeks:

  * Recombinant MVA-BN-Brachyury (R2PD): 4 injections of vaccines with 1 given subcutaneous (SC) in each extremity on Day 1 of Cycles 1 and 2. Each injection of MVA-BN-Brachyury consists of 2.0 x 10(8) infectious units (Inf.U).
  * Recombinant fowlpox virus (FPV)-Brachyury: 1 injection given SC in one extremity on Day 1 of Cycles 3 and beyond. Each infection of FPV-Brachyury consists of 1.0 x 10(9) Inf.U.
* adotrastuzumab emtansine (T-DM1) 3.6mg/kg via intravenous (IV) infusion every (q)3 weeks on Day 1 of each cycle.
* M7824 2,400mg via IV infusion q3 weeks on Day 1 of each cycle.
* Entinostat 5mg by mouth weekly recommended phase 2 dose (RP2D) administered by patient on Days 1, 8 and 15 of each cycle.

BN-Brachyury, Entinostat, Adotrastuzumab Emtansine and M7824 in Advanced Stage Breast Cancer (BrEAsT)

A Phase 1b Trial of Sequential Combinations of BN-Brachyury, Entinostat, Ado-trastuzuamb Emtansine and M7824 in Advanced Stage Breast Cancer (BrEAsT)

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Overall response is defined as the best response (Partial Response + Complete Response) recorded from the start of treatment until disease progression/recurrence assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progression is at least a 20% increase in the sum of diameters of target lesions. appearance of new lesions. Appearance of one or more new lesions.

Overall response is defined as the best response (Partial Response + Complete Response) recorded from the start of treatment until disease progression/recurrence. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progression is at least a 20% increase in the sum of diameters of target lesions. appearance of new lesions. Appearance of one or more new lesions.

Adverse events were recorded using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.

Progression free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. In the absence of progression or death, PFS is censored at the date of last disease evaluation. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1 and is defined as at least a 20% increase in the sum of diameters of target lesions. appearance of new lesions. Appearance of one or more new lesions.

The absolute percentage of stromal TILs was measured by the Salgado method in metastatic deposits in participants with metastatic HER2+ metastatic breast cancer. The Salgado method is a standardized approach for measuring the percentage of stromal TILs in primary breast tumor specimens before therapy, using visual assessment of standard hematoxylin and eosin (H\&E)-stained sections.

National Cancer Institute (NCI)

No participants were enrolled in group 2 and 3 due to study closure by the sponsor.

Arm 1 - Triple Negative Breast Cancer.

Bifunctional fusion molecule involving programmed death-ligand 1 (PD-L1) with transforming growth factor beta (TGF-b) sequestering agent added to a vaccine for the tumor associated antigen called brachyury.

Brachyury-TRICOM: Every three weeks, until cycle 9, then every 12 weeks: \*Recombinant MVA-Bavarian Nordic (BN)-Brachyury recommended phase 2 dose (R2PD): 4 injections of vaccines with 1 given subcutaneous (SC) in each extremity on Day 1 of Cycles 1 and 2. Each injection of MVA-BN-Brachyury consists of 2.0 x 10\^8 infectious units (Inf.U). \*Recombinant fowlpox virus (FPV)-BN-Brachyury: 1 injection given SC in one extremity on Day 1 of Cycles 3 and beyond. Each injection of FPV-BN-Brachyury consists of 1.0 x 10\^9 Inf.U.

M7824: 1800mg via intravenous (IV) infusion every (q)3 weeks on Day 1 of each cycle.

1/M7824 (Bintrafusp Alfa) + Bavarian Nordic (BN)-Brachyury

Arm 2 - Estrogen receptor (ER)-/progesterone receptor (PR)-/Human Epidermal Growth Factor Receptor 2 (HER2) + Breast Cancer.

Bifunctional fusion molecule involving programmed death-ligand 1 (PD-L1) with transforming growth factor beta (TGF-b) sequestering agent added to a vaccine for the tumor associated antigen called brachyury. These investigational agents will be added to standard of care treatment called Ado-trastuzumab emtansine (T-DM1).

Brachyury-TRICOM: Every three weeks, until cycle 9, then every 12 weeks: \*Recombinant MVA-Bavarian Nordic (BN)-Brachyury recommended phase 2 dose (R2PD): 4 injections of vaccines with 1 given subcutaneous (SC) in each extremity on Day 1 of Cycles 1 and 2. Each injection of MVA-BN-Brachyury consists of 2.0 x 10\^8 infectious units (Inf.U). \*Recombinant fowlpox virus (FPV)-BN-Brachyury: 1 injection given SC in one extremity on Day 1 of Cycles 3 and beyond. Each injection of FPV-BN-Brachyury consists of 1.0 x 10\^9 Inf.U.

M7824: 1800mg via intravenous (IV) infusion every (q)3 weeks on Day 1 of each cycle.

Ado-trastuzumab emtansine: 3.6mg/kg via intravenous (IV) infusion every (q)3 weeks on Day 1 of each cycle.

2/M7824 + BN-Brachyury + Ado-trastuzumab Emtansine (T-DM1)

Arm 3 - Estrogen receptor (ER)-/progesterone receptor (PR)-/Human Epidermal Growth Factor Receptor 2 (HER2)+ Breast Cancer.

Bifunctional fusion molecule involving programmed death-ligand 1 (PD-L1) with transforming growth factor beta (TGF-b) sequestering agent added to a vaccine for the tumor associated antigen called brachyury as well as to an oral histone deacetylase (HDAC) inhibitor called entinostat. These investigational agents will be added to standard of care treatment called Ado-trastuzumab emtansine (T-DM1). (T-DM1).

Brachyury-TRICOM: Every three weeks, until cycle 9, then every 12 weeks: \*Recombinant MVA-Bavarian Nordic (BN)-Brachyury recommended phase 2 dose (R2PD): 4 injections of vaccines with 1 given subcutaneous (SC) in each extremity on Day 1 of Cycles 1 and 2. Each injection of MVA-BN-Brachyury consists of 2.0 x 10\^8 infectious units (Inf.U). \*Recombinant fowlpox virus (FPV)-BN-Brachyury: 1 injection given SC in one extremity on Day 1 of Cycles 3 and beyond. Each injection of FPV-BN-Brachyury consists of 1.0 x 10\^9 Inf.U.

Entinostat: 5mg by mouth weekly (RP2D) administered by patient on Days 1, 8 and 15 of each cycle.

M7824: 1800mg via intravenous (IV) infusion every (q)3 weeks on Day 1 of each cycle.

Ado-trastuzumab emtansine: 3.6mg/kg via intravenous (IV) infusion every (q)3 weeks on Day 1 of each cycle.

3/M7824 + BN-Brachyury + T-DM1 + Entinostat

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Fatima H. Karzai

Complete Response

Partial Response

Progressive Disease

This outcome measure pertains to Arm 1 TNBC participants only.

Overall Response (Partial Response + Complete Response) for Participants With Triple Negative Breast Cancer (TNBC)

This outcome measure pertains to Arm 2 and 3 only. Overall response in the HER2+ breast cancer cohort was not assessed as the study closed to accrual and no participants with HER2+ breast cancer was accrued.

Overall Response (Partial Response + Complete Response) for Participants With Human Epidermal Growth Factor Receptor 2 (HER2) + Breast Cancer (BC)

Grade 3

Grade 4

Grade 5

Number of Participants Experiencing at Least One Grade 3 to 5 Adverse Events for Each of the Three Combinations of Agents

Progression-free Survival (PFS) in Triple Negative Breast Cancer (TNBC)

This outcome measure pertains to Arm 2 and 3 only. PFS in the HER2+ breast cancer cohort was not assessed as the study closed to accrual and no participants with HER2+ breast cancer was accrued.

Progression Free Survival (PFS) in Participants With Metastatic Hormone Receptor (HR)-/Human Epidermal Growth Factor Receptor 2 (HER2) + Metastatic Breast Cancer Who Progressed on Initial Treatment With THP

Progression Free Survival (PFS) in Participants With Metastatic Human Epidermal Growth Factor Receptor 2 (HER2+) Metastatic Breast Cancer Who Progressed on Initial Treatment With Docetaxel (THP)

This outcome measure pertains to Arm 2 and 3 only. No participants with HER2+ metastatic breast cancer was accrued and thus outcome measure is not possible to determine.

Absolute Percentage of Stromal Tumor Infiltrating Lymphocytes (TILs) in Metastatic Deposits in Participants With Metastatic Human Epidermal Growth Factor Receptor 2 (HER2+) Metastatic Breast Cancer

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Overall Study

Symptoms and General Pathology

Recurrence

Gemcitabine

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Antimetabolites

Treatment Arm A: nab-Paclitaxel 125 mg/m\^2 by intravenous (IV) administration over 30 minutes, followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 of each 21-day cycle by IV administration over 30 minutes

Treatment Arm B: nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin at an Area Under the Curve (AUC) of 2 on Days 1 and 8 of each 21-day cycle by IV administration

Treatment Arm C: Gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin AUC 2 on Days 1 and 8 of each 21-day cycle by IV administration

nab-Paclitaxel 125 mg/m\^2 by IV administration over 30 minutes on Days 1 and 8 of each 21-day treatment cycle.

nab-Paclitaxel

Carboplatin at an AUC of 2 on Days 1 and 8 of each 21-day cycle by IV administration

Gemcitabine 1000 mg/m\^2 on Days 1 and 8 of each 21-day treatment cycle.

Ileana Elias, M.D.

The purpose of this study is to compare the safety and efficacy of nab-paclitaxel in combination with either gemcitabine or carboplatin to the combination of gemcitabine and carboplatin as first line treatment in female subjects with triple negative metastatic breast cancer (TNMBC) or metastatic triple negative breast cancer.

ABI-007-MBC- 001 is a Phase 2/3, multicenter, open-label, randomized, study that will compare the safety and efficacy of weekly nab-paclitaxel in combination with gemcitabine or carboplatin to the combination of gemcitabine and carboplatin as first line therapy in female subjects with Estrogen Receptor (ER), Progesterone Receptor (PgR), and human epidermal growth factor receptor 2 (HER2) negative (triple negative) metastatic breast cancer (TNMBC) or metastatic triple negative breast cancer. In the phase 2 portion of the study, the combinations of nab-paclitaxel plus gemcitabine and nab-paclitaxel plus carboplatin will be evaluated, and a comparator arm of gemcitabine combined with carboplatin will be used. In the phase 3 portion of the study, the selected nab-paclitaxel combination treatment will be compared to gemcitabine combined with carboplatin to evaluate progression free survival, safety and tolerability, overall survival, disease control rate and duration of response in women with metastatic triple negative breast cancer.

Due to changes in the treatment landscape since the initiation of this trial, the decision was made not to proceed to the Phase 3 portion of the study.

Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

A Phase 2/3, Multi-Center, Open-Label, Randomized Study of Weekly Nab®-Paclitaxel in Combination With Gemcitabine or Carboplatin, Compared to Gemcitabine/Carboplatin, as First Line Treatment in Subjects With ER, PgR, and HER2 Negative (Triple Negative) Metastatic Breast Cancer

PFS was defined as the time from the date of randomization to the date of disease progression or death from any cause on or prior to the data cutoff date for the statistical analysis, whichever occurred earlier. Tumor responses were assessed every 6 weeks using, Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and defined as: Complete response (CR) is the disappearance of all target lesions; Partial response (PR) occurs when at least a 30% decrease in the sum of diameters of target lesions from baseline; Stable disease is neither sufficient shrinkage to qualify for a PR nor sufficient increase of lesions to qualify for Progressive disease (PD); Progressive Disease- is at least a 20% increase in the sum of diameters of target lesions from nadir.

Percentage of participants with an Objective Complete or Partial Overall Response according to RECIST 1.1 and defined as: Complete response-disappearance of all target lesions; partial response at least a 30% decrease in the sum of diameters of target lesions from baseline; stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD)• Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.

The percentage of participants who initiated Cycle 6 receiving doublet combination therapy regardless of the need for dose modifications.

Overall survival was defined as the time from the date of randomization to the date of death (from any cause).

Treatment-emergent adverse events (TEAEs) were defined as any AEs that began or worsened with the onset date on or after the date of the first dose of IP through 28 days after the last dose. A serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was graded based on the participant's symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity as follows: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death.

The number of participants with dose modifications occurring during the treatment period. Dose reductions and interruptions are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.

Treatment-emergent adverse events (TEAEs) were defined as any AEs that begin or worsen with an onset date on or after the date of the first dose of IP through 28 days after the last dose.

Celgene

Maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B and 110.1 weeks for Arm C

Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration in each 21-day treatment cycle.

Arm A: Nab-Paclitaxel + Gemcitabine

Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by Carboplatin AUC 2 on Days 1 and 8 in each 21-day treatment cycle.

Arm B: Nab-Paclitaxel + Carboplatin

Participants received Gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle.

Arm C: Gemcitabine + Carboplatin

Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.

Arm A: Nab-Paclitaxel Plus (+) Gemcitabine

Participants received nab-Paclitaxel 125 mg/m\^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.

Participants received gemcitabine 1000 mg/m\^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.

Black or African American

White

Unknown or Not Reported

Race

0 = Fully Active

1 = Restrictive but ambulatory

2 = Ambulatory but unable to work

Missing

ECOG performance status is used by doctors and researchers to assess how a subject's disease is progressing, assess how the disease affects the daily living activities of the subject and determine appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity)

Eastern Cooperative Oncology Group (ECOG) Performance Status

≤ 1 year

> 1 year

Disease Free Interval is defined as period of being absent of disease less than or equal to one year or free of disease greater than one year.

Disease Free Interval by Clinical Interpretation

Time from Diagnosis to First Documented Disease/Relapse

Time from First Documented Metastatic Disease/Relapse to Study Randomization

Time from Primary Diagnosis to Randomization

Lymph Nodes(s)

Lung/Thoracic

Bone

Liver

Right/Left Breast

Current Sites of Metastasis

Intent-to-treat (ITT) population includes all randomized participants regardless of whether they received any IP or had any efficacy assessments collected.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
ETHAN - ET for Male BC	NCT05501704	Male Breast Can... Hormone Recepto... Hormone Recepto...	Tamoxifen Anastrozole Degarelix Abemaciclib	18 Years -	Dana-Farber Cancer Institute
BN-Brachyury, Entinostat, Adotrastuzumab Emtansine and M7824 in Advanced Stage Breast Cancer (BrEAsT)	NCT04296942	Breast Cancer Triple Negative... HER2+ Breast Ca... Hormone Recepto... Metastatic Brea...	Brachyury-TRICO... Entinostat M7824 Ado-trastuzumab...	18 Years -	National Institutes of Health Clinical Center (CC)
ETHAN - ET for Male BC	NCT05501704	Male Breast Can... Hormone Recepto... Hormone Recepto...	Tamoxifen Anastrozole Degarelix Abemaciclib	18 Years -	Dana-Farber Cancer Institute
ETHAN - ET for Male BC	NCT05501704	Male Breast Can... Hormone Recepto... Hormone Recepto...	Tamoxifen Anastrozole Degarelix Abemaciclib	18 Years -	Dana-Farber Cancer Institute
BN-Brachyury, Entinostat, Adotrastuzumab Emtansine and M7824 in Advanced Stage Breast Cancer (BrEAsT)	NCT04296942	Breast Cancer Triple Negative... HER2+ Breast Ca... Hormone Recepto... Metastatic Brea...	Brachyury-TRICO... Entinostat M7824 Ado-trastuzumab...	18 Years -	National Institutes of Health Clinical Center (CC)
Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)	NCT01881230	Breast Tumor Breast Cancer Cancer of the B... Estrogen Recept... HER2- Negative ... Progesterone Re... Recurrent Breas... Stage IV Breast... Triple-negative... Triple-negative... Metastatic Brea...	nab-Paclitaxel Carboplatin Gemcitabine	18 Years -	Celgene

Spots Global Cancer Trial Database for hormone receptor negative breast cancer