This study is being done to see how safe an investigational drug is and how well it will work to help people with ER+ (estrogen receptor positive), HER2- (human epidermal growth factor negative) breast cancer that is locally advanced or metastatic. "Investigational" means that the drug being tested has not been approved for routine clinical use or for the use described in this study by the United States Food and Drug Administration (FDA). The FDA is allowing the use of this drug for research.
The main reason for this study is to help answer the following research questions:
- How much LY3484356 should be given to study participants.
- The safety of LY3484356 and any side effects presented.
- Whether LY3484356 can help study participants with ER+, HER2 breast cancer that has advanced or endometrioid endometrial cancer that has advanced.
- Whether LY3484356 is tolerable when taken with abemaciclib.
Inova Schar Cancer Institute
8081 Innovation Park Dr.
Fairfax, VA 22031
A department of Inova Fairfax Hospital
3580 Joseph Siewick Dr., Suite 403
Fairfax, VA 22033
- Adults (18 years of age and older)
- Adequate organ function
- Have histological or cytological diagnosis of one of the following: locally advanced unresectable or mBC that is ER+, HER2-; or endometrioid endometrial cancer (EEC):
- Have had up to 3 prior regimens in the advanced/metastatic setting and fulfill one of the following:
I. Progression while on endocrine-containing therapy for ≥24 months in the adjuvant setting OR
II. Progression while on endocrine-containing therapy for ≥6 months in the advanced/metastatic setting
- To fulfill the requirement for ER+ disease by local testing, ≥1% of tumor cell nuclei must be immunoreactive by immunohistochemistry defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Guidelines
- To fulfill the requirement of HER2- disease by local testing on primary disease specimen, tumor must be HER2- according to ASCO/CAP guidelines for HER2 testing
- For ER+, EEC:
I. Have progressed after SOC therapy
II. Must have had prior platinum-containing therapy
- To fulfill the requirement for ER+ disease by local testing, ≥1% of tumor cell nuclei must be immunoreactive by immunohistochemistry defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Guidelines.
- For Phase 1a Dose Escalation: have one of the following as defined by RECIST v1.1:
I. Measurable disease
II. Nonmeasurable bone-only disease. Nonmeasurable bone-only diseasemay include any of the following:
i. blastic bone lesions
ii. lytic bone lesions without a measurable soft tissue component
iii. mixed lytic-blastic bone lesions without a measurable soft tissue component.
- For Phase 1b Dose Expansion: have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1
- Patients must be willing to provide an adequate archival tissue sample (primary or metastatic disease). Preferably, the most recently obtained nonbone biopsy should be provided.
- Additional eligibility in protocol.
- Inflammatory Breast Cancer
- Pregnant or breastfeeding
- Symptomatic central nervous system (CNS) metastasis and/or carcinomatous meningitis. Patients with treated CNS metastases are eligible for this study if they are not receiving corticosteroids and/or anticonvulsants for at least 14 days prior to first dose of study treatment, and their disease is asymptomatic and radiographically stable for at least 30 days prior to consent by repeat imaging (repeat imaging should be performed during study screening). Patients with untreated stable or asymptomatic brain metastases are eligible.
- Serious concomitant systemic disorder (eg, active infection or a gastrointestinal disorders causing clinically significant symptoms such as nausea, vomiting, or diarrhea, or profound immune suppression) that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol, including but not limited to the following:
I. Human immunodeficiency virus (HIV) positive patients (HIV 1 and/or 2; screening not required) are excluded unless they are well controlled on highly active antiretroviral therapy with - No evidence of autoimmune deficiency syndrome-defining opportunistic infections within the last 2 years, and - CD4 count > 350 cells/μL
II. Active hepatitis B or C virus infection (screening not required)
III. Severe renal impairment, interstitial lung disease (ILD), severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis or a preexisting chronic condition resulting in clinically significant diarrhea
- Pre-existing nausea, vomiting or diarrhea > Grade 1 per CTCAE 5.0. If this toxicity is related to prior therapy, must be resolved to < Grade 1 to go on study.
- Visceral crisis. Visceral crisis is not the mere presence of visceral metastases but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies and rapid progression of the disease.
- Additional ineligibility in protocol.
Additional information can be found at: https://clinicaltrials.gov/ct2/show/NCT04188548