Inclusion Criteria
- Part 1: Breast Cancer (BC)
- Refractory Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) BC
- Part 1A/Part 1D/Part 1E also include: Refractory HR-positive/HER2-positive BC
- Part 1: Tumors other than BC (Part 1A/Part 1D/Part 1E): NSCLC, prostate, CRC, liposarcoma, or tumors with previously confirmed CDK4 or CCND1 amplification according to local standard tests
- Part 1F: prostate cancer
- Part 1G: HR-positive/HER2-negative BC
- Part 2A, 2B, 2C, 2E, and 2F: HR-positive/HER2-negative BC
- Part 1D: metastatic castration resistant prostate cancer
- Giredestrant Combination Cohort: ER-positive/HER2-negative BC
- Prior systemic Treatment
- Part 1: HR-positive/HER2-negative BC
- At least 1 line of SOC, including CD4/6 inhibitor therapy for advanced or metastatic disease, or if CDK4/6 inhibitors are not considered appropriate in the opinion of the investigator
- HR-positive/HER2-positive BC (Parts 1A/1D/1E): at least 1 prior treatment of approved HER2 targeting therapy
- Tumors other than BC (Parts 1A/1D/1E/1F): tumor that is resistant to at least 2 lines of SOC for advanced or recurrent disease or for which no standard therapy is available
- Part 2A and 2E: at least 1 line of standard of care (including prior CDK4/6i) for advanced/metastatic disease; Prior chemo is allowed; Prior fulvestrant, mTOR and/or PI3K inhibitors are allowed
- Part 2B: no prior systemic anti-cancer therapies for advanced/metastatic BC
- Part 2C:
- Progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre or perimenopausal, or
- Progressed while on or within 1 month after the endo the prior aromatase inhibitor therapy for advanced/metastatic BC if postmenopausal or prior endocrine treatment for advanced/metastatic BC if pre or perimenopausal
- One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy
- Part 1G and 2F: at least 2 lines of SOC for advanced or metastatic disease, including CDK4/6 inhibitor and endocrine therapy
- Giredestrant Combination Cohort: at least 1 (no more than 3) prior line(s) of SOC for advanced or metastatic disease, including CDK4/6 inhibitor and endocrine therapy
General Inclusion Criteria
- All participants must be refractory to or intolerant of existing therapies known to provide clinical benefit for their condition.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
- Adequate renal, liver, and bone marrow function
Exclusion Criteria:
- Part 2B: prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor with disease recurrence while on or within 12 months of completing treatment. Prior treatment with any CDK4/6 inhibitor
- Part 2C: prior treatment with any CDK inhibitor, fulvestrant, everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway
- Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases carcinomatous meningitis, or leptomeningeal disease
- Other active malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
- Major surgery or radiation within 4 weeks prior to study intervention
- Last anti-cancer treatment within 2 weeks prior to study intervention; Part 1G and 2F: tamoxifen treatment within 35 days of Day -4
- Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry
- Part 1G and 2F: history of or current pulmonary embolism or deep vein thrombosis
- Giredestrant Combination Cohort: history (within 6 months of screening) of or presence of idiopathic symptomatic bradycardia or resting heart rate <50 bpm at screening
- Pregnant or breastfeeding female participant
- Active inflammatory gastrointestinal (GI) disease, known diverticular disease or previous gastric resection or lap band surgery including impairment of gastrointestinal function or GI disease
