Breast Cancer

Retrospective Observational Study of Hormone Receptor Positive (HR+) and HER2-low (IHC1+ or 2+ with ISH negative) and HER2- ultralow (IHC0 with membrane staining) Metastatic Breast Cancer (MBC)

Brief Summary: This is a multicenter retrospective observational study in participants with HR+ HER2-low and HER2-ultralow MBC. ENHERTU treatment should have been received on or after September 2022 and other treatments could have been received prior to September 2022

Key Eligibility Criteria:

• HR+ HER2-low and HER2-ultralow MBC participants who have received at least 2 cycles of treatment with ENHERTU
• HR+ HER2 negative defined as IHC0 without membrane staining excluded
• HR+ HER2-positive excluded
• HR- HER2-positive, HER2-low, HER2-ultralow and negative excluded

CTC-EXPRESS: A Prospective Observational Study for CTC Expression and cfDNA/RNA Assessment in Metastatic Breast Cancer

Brief Summary: The purpose of this research is to learn if the CellSearch Circulating Tumor Cells (CTC) test can help doctors in making decisions about treatment and monitoring of breast cancer. The test consists of diagnostic CTC counts (enumeration) and expression of biomarkers Human Epidermal growth factor Receptor 2 (HER2), Estrogen Receptor (ER), and programmed death-ligand 1 (PD-L1) and cell free DNA/RNA (cfDNA/RNA) analysis.

Key Eligibility Criteria:

• Invasive breast cancer with radiographic and/or clinical evidence of advanced metastatic or unresectable disease.
• HR+/HER2 negative or triple negative (TN) subjects prior to starting first line therapy or beyond in the metastatic setting.
• OR HER2+ subjects prior to starting second line therapy or beyond in the metastatic setting.
  • Subject must have the CTC HER2, ER, PD-L1, and cfDNA/RNA tests ordered during routine patient care.
• Participant is pregnant excluded.
• Inability to provide blood samples based on the judgment of the treating physician excluded.

PALbociclib CoLlaborative Adjuvant Study: A Randomized Phase III Trial of Palbociclib With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone for Hormone Receptor Positive (HR+) / Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Early Breast Cancer

Brief Summary: This is a prospective, two arm, international, multicenter, randomized, open-label Phase III study evaluating the addition of 2 years of palbociclib to standard adjuvant endocrine therapy for patients with HR+ / HER2- early breast cancer (EBC).

Key Eligibility Criteria:

• Pre- and postmenopausal women or men with Stage II (Stage IIA limited to max. 1000 patients) or Stage III early invasive breast cancer.
• Patients with multicentric and/or multifocal and/or bilateral early invasive breast cancer are eligible if all histopathologically examined tumors meet pathologic criteria for ER+ and/or PR+ and HER2-.
• Patients must have histologically confirmed ER+ and/or PR+, HER2-, early invasive breast cancer.
• Patients must have undergone adequate (definitive) breast surgery for the current malignancy.
• Patients who already received neo/adjuvant endocrine therapy are eligible as long as they are enrolled within 12 months of initial histological diagnosis and after completing no more than 6 months of adjuvant endocrine therapy.
• Prior therapy with any CDK inhibitor excluded.
• Patients with Stage I or IV breast cancer are not eligible.

A phase IIIb study to characterize the efficacy and safety of ADJUVANT ribociclib plus endocrine therapy in a close-to-clinical practice patient population with HR+ HER2- early breast cancer (ADJUVANT WIDER)

MOA: Aromatase inhibitor, CDK4/6 inhibitor, LHRH agonist

Key Eligibility Criteria:

• Participant has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer (BC)Participant has HER2- BC
• Participant has no contraindication to receive adjuvant ET in the study.
• Participant after surgical resection where tumor was removed completely, with the final surgical specimen microscopic margins free from tumor, and belongs to one of the following categories:
  • Anatomic Stage Group III, or
  • Anatomic Stage Group IIB, or
  • A subset of Anatomic Stage Group IIA.
• Participant without distant metastases of BC beyond regional lymph nodes (Stage IV according to AJCC 8th edition) and/or evidence of recurrence after curative surgery.
• Participant is not concurrently using other antineoplastic therapy with the exception of adjuvant ET.

Randomised, Open-Label, Phase III Study of Saruparib (AZD5305) Plus Camizestrant versus Physician's Choice CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant for the First-Line Treatment of BRCA1, BRCA2, or PALB2 Mutations and Hormone Receptor-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH non-amplified) Advanced Breast Cancer (EvoPAR-Breast01)(D9722C00001)

MOA: Saruparib (AZD5305) is a selective inhibitor of PARP1, with minimal effect on PARP2. Camizestrant (AZD9833) is a next generation SERD with activity in both ESR1 mutant and WT settings.

Key Eligibility:

• Histologically or cytologically documented HR-positive (ER > 1%), HER2-negative (IHC 0/1+ or IHC 2+/ ISH-) based on local testing
• Locally advanced/metastatic breast cancer with no prior systemic therapy in the advanced/metastatic setting
• Participants must have BRCA1/2 or PALB2 loss of function mutation prior to screening, either germline (local testing) or somatic (central testing)
• Pre/peri-menopausal women and males must be on an LHRH agonist
• Measurable disease by RECIST 1.1
• Disease progression ≤84 days following (neo)adj tx for EBC excluded
• Disease progression ≤1 year from last dose of PARPi, platinum-agent, CDK4/6i, or oral SERD for EBC excluded

Elacestrant versus Standard Endocrine Therapy in Women and Men with Node -positive, Estrogen Receptor-positive, HER2-negative, Early Breast Cancer with High Risk of Recurrence - A Global, Multicenter, Randomized, Open-label Phase 3 Study (ELEGANT)(STML-ELA-0422)

MOA: Elacestrant is an oral SERD and ER antagonist.

Key Eligibility Criteria:

• Women or men with confirmed ER-positive (≥10% by IHC), HER2-negative [IHC = 0 or 1, or (IHC = 2 and ISH-negative)] early stage resected BC without evidence of recurrence or distant metastases
  • Pts should be between 2 to 6 years from the date of curative surgical resection
• Pts should have received ≥24 mo and <60 mo of ET(AIs or tamoxifen) with/without a CDK4/6i and with/without an LHRH agonist
  • Pts who received prior CDK4/6i or PARP inhibitor must have already completed or discontinued these treatments
• Pt must be considered candidate for additional 5 years of ET
• Pts considered at high risk of recurrence at pathologic staging
  • ≥ 4 positive axillary lymph nodes or
  • 1-3 positive axillary lymph nodes and
    • Histologic grade 3 disease or
    • Tumor size ≥ 5 cm.
• Male pts receiving AI or elacestrant must receive an LHRH agonist

A Phase 3, randomized, open-label, multicenter, controlled study to evaluate the efficacy and safety of zanidatamab in combination with physician's choice chemotherapy compared to trastuzumab in combination with physician's choice chemotherapy for the treatment of participants with metastatic HER2-positive breast cancer who have progressed on, or are intolerant to, previous trastuzumab deruxtecan treatment (JZP598-303)

MOA: Zanidatamab is a bispecific antibody targeting two distinct HER2 epitopes, ECD2 and ECD4.

Key Eligibility Criteria:

• Women and men with HER2-positive metastatic breast cancer
• Central testing of HER2 status must be performed w/in 6 mo prior to C1D1
• Most recent archival tissue or fresh biopsy must be submitted to confirm HER2 status by sponsor-designated central lab prior to randomization
• If pt meets all eligibility criteria but HER2 status is not confirmed, pts with previously assessed IHC 3+ HER2+ status will be randomized while tissue is submitted to central lab for HER2 confirmation
• Pt must have progressed on, or is intolerant to, previous T-DXd treatment
• Pt must have received 2-4 lines of HER2-directed tx in metastatic setting
• Prior HER2-targeted (neo)adj therapy that resulted in relapse w/in 6 mo considered line of therapy for metastatic disease
• Post-T-DXd therapy allowed (for ex: tucatinib-based regimen and/or T-DM1)
• Measurable disease per RECIST v1.1

A Phase III, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) with or without Durvalumab compared with Investigator's Choice of Chemotherapy (Paclitaxel/Nab-paclitaxel or Gemcitabine+ Carboplatin) in combination with Pembrolizumab in Patients with PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (TROPIONBreast05)

MOA: Anti-PD-1 monoclonal antibody, Anti-PD-L1 (CD274) monoclonal antibody, Platinum compound, Ribonucleotide reductase inhibitor, Pyrimidine antagonist, TROP-2-targeted ADC, Taxane

Key Eligibility Criteria:

• Histologically or cytologically documented locally recurrent inoperable, which cannot be treated with curative intent, or metastatic TNBC, as defined by the ASCO-CAP guidelines
• No prior chemotherapy or other systemic anti-cancer therapy for metastatic or locally recurrent inoperable breast cancer.
• Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin).
• Adequate bone marrow reserve and organ function.
• As judged by investigator, any evidence of diseases which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol
• No history of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before Cycle 1 Day 1 and of low potential risk for recurrence.

Open-label, Safety Extension Study for Subjects with Hormone-Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer Who Have Completed the OVarian Suppression Evaluating Subcutaneous LeuprolIde Acetate in Breast Cancer (OVELIA) Study (TOL2506A-EXT)

MOA: Aromatase inhibitor, First-generation selective estrogen receptor modulator (SERM)

Key Eligibility Criteria:

• Diagnosis of Stage I, II, or III HR+, HER2-negative breast cancer (ER>1% and/or, PR>1%, HER2-negative per ASCO CAP guidelines)
• Is a candidate for endocrine therapy + ovarian suppression LH > 4 IU/L within 28 days prior to Day 1
• Is premenopausal
• No prior (within 28 days prior to Day 1) and/or concomitant use of medications known to prolong the QT/QTc interval
• No prior use of tamoxifen, other SERMs (eg, raloxifene) or antagonists (eg, fulvestrant), aromatase inhibitor, mammalian target of rapamycin (mTOR) inhibitors, or hormone replacement therapy within 3 months before breast cancer diagnosis
• No prior neoadjuvant or adjuvant endocrine therapy since diagnosis of breast cancer

Phase 2 Single Arm Trial with a Safety Lead-in of Tucatinib in Combination with Doxil for the Treatment of HER2+ Metastatic Breast Cancer (BRE 381)

MOA: Tucatinib is an oral tyrosine kinase inhibitor selective for HER2 Doxil is an anthracycline topoisomerase II inhibitor

Key Eligibility Criteria:

• Women, men with HER2+ metastatic breast cancer (IHC3+ or FISH+)
• Prior tx with at least 1L anti-HER2 therapy in metastatic setting or relapsed w/in 6 mo of completion of adjuvant anti-HER2 therapy
  • Prior tx with tucatinib in metastatic setting allowed
  • Prior tx with anthracycline (any setting) excluded
• Measurable disease per RECIST v1.1
• CNS Inclusion – patients must have one of the following:
  • No evidence of brain metastases
  • Untreated brain metastases not needing immediate local therapy. Lesions >2.0 cm require approval from Medical Monitor.
  • Previously treated brain metastases that are stable or have progressed but do not require immediate re-treatment
    • Time since WBRT ≥14 days prior to first dose of tx
    • Time since SRS ≥7 days prior to first dose of tx
    • Time since surgical resection ≥28 days

A Phase Ib/III, Open-label, Randomised Study of Capivasertib plus CDK4/6 Inhibitors and Fulvestrant versus CDK4/6 Inhibitors and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer (CAPItello-292)

MOA: Capivasertib is an oral pan-AKT inhibitor

Key Eligibility Criteria:

• Men and women with adv/metastatic HR+/HER2- breast cancer
• Pre-/perimenopausal women, men must receive concurrent tx w/ LHRH
  agonist
• Pt must have progressed on or w/in 12 months of (neo)adjuvant ET
  (single agent or in combo)
• Maximum 1L chemotherapy in metastatic setting
• Measurable disease per RECIST v1.1 or lytic/mixed bone lesion
• Mandatory FFPE tumor sample for central testing
• Mandatory blood samples at screening for central testing
• Previous tx w/ AKT, PI3K, mTOR inhibitors excluded
• Endocrine-based therapy or CDK4/6i in metastatic setting excluded

A PHASE III RANDOMIZED, OPEN-LABEL STUDY EVALUATING EFFICACY AND SAFETY OF GIREDESTRANT COMPARED WITH FULVESTRANT, BOTH COMBINED WITH A CDK4/6 INHIBITOR, IN PATIENTS WITH ESTROGEN RECEPTOR-POSITIVE, HER2-NEGATIVE ADVANCED BREAST CANCER WITH RESISTANCE TO PRIOR ADJUVANT ENDOCRINE THERAPY (CO44657)

MOA: Giredestrant is an oral selective estrogen receptor degrader (SERD)

Key Eligibility Criteria:

• Locally advanced or metastatic ER+(≥1%)/HER2- BC
• Confirmed ESR1 mutation status [ESR1m vs ESR1nmd]
  • Central testing (F1LCDx)
• Relapsed on standard adjuvant ET with AI and/or SERM
  • On-treatment after ≥12 months
  • Off-treatment within 12 months of completion
  • If CDK4/6i, relapse ≥12 months since completion
• No prior tx in metastatic setting
• Measurable disease or evaluable bone-only disease per RECIST v1.1
• Prior tx w/ SERD, proteolysis tarting chimera, CERAN, novel SERM excluded

A Phase 3, Randomized, Multi-center, Open-label Study of DB-1303 Versus Investigator's Choice Chemotherapy in Human Epidermal Growth Factor Receptor 2 (HER2)-low, Hormone Receptor Positive (HR+) Metastatic Breast Cancer Patients whose Disease has Progressed on Endocrine Therapy (ET) (DYNASTY-Breast02)

MOA: DB-103 is a HER2- targeting ADC with a DNA topoisomerase I inhibitor (P1003) payload

Key Eligibility Criteria:

• Pathologically documented advanced/metastatic BC
  • HER2-low (IHC1+ or IHC2+/ISH-) as determined by central lab
  • Never previously reported as HER2-positive
  • Documented as HR+ (ER and/or PgR ≥1%)
  • Adequate tumor tissue sample for HER2 assessment by central lab
• Disease progression on ET + CDK4/6 inhibitor w/in 6 months of starting 1L or on at least 2 lines of ET with or without targeted therapy
• No prior chemotherapy for mBC
• Previous treatment with anti-HER2 therapy or with ADC comprising an exatecan derivative excluded

CAMBRIA-2: A Phase III, Open-Label, Randomised Study to Assess the Efficacy and Safety of Camizestrant (AZD9833, a Next Generation, Oral Selective Estrogen Receptor Degrader) vs Standard Endocrine Therapy (Aromatase Inhibitor or Tamoxifen) as Adjuvant Treatment for Patients With ER+/HER2- Early Breast Cancer and an Intermediate-high or High risk of Recurrence Who Have Completed Definitive Locoregional Treatment and Have No Evidence of Disease (D8535C00001)

MOA: Camizestrant is an oral selective estrogen receptor degrader (SERD)

Key Eligibility Criteria:

• ER+ (>10%)/HER2-negative early-stage invasive BC with no evidence of metastatic disease
• Pts must meet criteria for high or intermediate-high risk of recurrence
• Completed breast surgery +/- radiotherapy, +/- (neo)adj chemo
• Pts must be randomized w/in 12 weeks after RT or last dose of chemotherapy. Pts may have received up to 12 weeks of ET in (neo)adjuvant setting prior to randomization
• Pts may have received abemaciclib up to 12 weeks prior to randomization
• Pts with pCR or RCB-0 after neoadjuvant chemo are excluded
• Pts must be randomized within 12 months of breast surgery

A Randomized, Multicenter, Placebo-controlled, Phase 3 study to Evaluate the Efficacy and Safety of HER2/neu Peptide GLSI-100 (GP2 + GM-CSF) in HER2/neu Positive Subjects with Residual Disease or High-Risk PCR after both Neoadjuvant and Postoperative Trastuzumab-based Therapy (FLAMINGO-01)

MOA: GLSI-100 is the individual administration of GP2, a nine amino acid peptide of the HER2/neu protein, and GM-CSF. GLSI-100 induces a CD8+ T cell response targeted to HER2- positive cells

Key Eligibility Criteria:

• Histologically confirmed HER2+ primary BC
• HLA-A02 positive, unless being enrolled in non-HLA-A02 arm
• Stage I, II, or III at presentation with residual disease at surgery or
  Stage III at presentation with pCR at surgery
• Completion of primary standard of care BC therapy
• Neoadjuvant systemic treatment consisting of at least 6 cycles of
  chemotherapy with total duration of at least 16 weeks
• Must include 9 weeks of trastuzumab (or approved biosimilar) and
  taxane based chemo – finished within one year of starting study
• Surgery
• At least 90% of planned trastuzumab-based (or approved biosimilar)
  treatment post-surgery
• Patients may continue hormone-based therapy but must not be
  receiving chemotherapy. Concurrent neratinib is prohibited.
• No clinical evidence of residual BC; Stage IV disease excluded

MammaPrint, BluePrint, and Full-genome Data Linked with Clinical Data to Evaluate New Gene Expression Profiles: An Adaptable Registry (FLEX Registry)

Brief Summary:  The FLEX Registry will be implemented to operate as a large-scale, population based, prospective registry. All patients with stage I to III breast cancer who receive MammaPrint® and BluePrint testing on a primary breast tumor are eligible for entry into the FLEX Registry, which is intended to enable additional study arms at low incremental effort and cost. FLEX Registry will utilize an adaptive design, where additional targeted substudies and arms can be added after the initial study is opened.

Key Eligibility Criteria:

• Stage I, II, or III patients who receive MammaPrint, with or without BluePrint testing (male or female)
• Informed consent form signed on the same day or before enrollment
• New primary lesion
• Tumor sample shipped to Agendia with ≤ 30% tumor cells or that fails QA or QC criteria excluded
• Metastatic disease excluded
• Recurrent disease excluded
• Stage 0 disease excluded