Expanded Access Program to Provide Giredestrant to Participants With ER+, HER2- Early or Locally Advanced/Metastatic Breast Cancer

General Inclusion Criteria:

- Documented ER-positive tumor according to American Society of Clinical
Oncology/College of American Pathologists (ASCO/CAP) guidelines (Allison et al
2020), defined as ≥1% of tumor cells stained positive, as documented through local
laboratory testing of a primary disease specimen

- Documented HER2-negative tumor according to ASCO/CAP guidelines (Wolff et al. 2023),
as documented through local laboratory testing of a primary disease specimen

- Adequate hematologic and organ function at screening

- Resolution of all acute toxic effects of prior anti-cancer therapy or surgical
procedures to CTCAE v6.0 Grade 1 or better (except alopecia, Grade ≤2 peripheral
neuropathy, or other toxicities not considered a safety risk for the participant per
treating physician's judgment)

- Agreement to adhere to the contraception requirements

- For women: postmenopausal, premenopausal, or perimenopausal status, defined as
follows:

1. Postmenopausal status, as defined by at least one of the following criteria:
Amenorrhea for ≥12 continuous months with no identified cause other than
menopause. If clinically justified or if there is any doubt of postmenopausal
state, a high blood follicle-stimulating hormone level in the postmenopausal
range may be used to confirm a postmenopausal state in participants who are not
using hormonal contraception or hormonal replacement therapy. Further guidance
for these exceptional circumstances is provided in "Recommendations related to
contraception and pregnancy testing in clinical trials" (CTFG 2020). Documented
bilateral oophorectomy (≥14 days prior to first treatment on Day 1 of Cycle 1
and recovery from surgery to baseline), hysterectomy, or bilateral
salpingectomy.

2. Premenopausal or perimenopausal status, as defined by not meeting the above
criteria for postmenopausal status.

- For premenopausal or perimenopausal women and men (except men with documented
bilateral orchiectomy): agreement to receive treatment with an approved luteinizing
hormone-releasing hormone (LHRH) agonist for the duration of the EAP treatment LHRH
agonist therapy may be initiated up to 28 days prior to Day 1 of Cycle 1 (or as per
clinical practice for the selected agent). To minimize the potential decrease of
LHRH agonist to subtherapeutic levels towards the end of the treatment cycle,
monthly injections of LHRH agonist are preferred and must be synchronized with Day 1
of each 28-day cycle. Known allergy or hypersensitivity to LHRH agonist therapy is
exclusionary.

- Ability to swallow capsules or tablets intact, without chewing or crushing

Inclusion Criteria for Early Breast Cancer (eBC) Cohort:

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

- Definitive surgery of primary breast tumor(s) and axillary lymph nodes dissection
(ALND) and/or sentinel lymph node biopsy (SLNB)

- For individuals who have received neoadjuvant chemotherapy and/or had definitive
breast cancer surgery and no prior endocrine therapy: surgery must have been
performed within 12 months prior to enrollment

- For individuals who have received adjuvant chemotherapy: adjuvant chemotherapy must
have been completed prior to enrollment. A washout period of at least 21 days is
required between last adjuvant chemotherapy dose and enrollment in EAP.

- Stage I, II, or III breast cancer, with medium or high risk of recurrence

Inclusion Criteria for Locally Advanced/Metastatic Breast Cancer (LA/mBC) Cohort:

- Locally advanced unresectable or metastatic adenocarcinoma of the breast, not
amenable to treatment with curative intent

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

- Disease progression after ≥6 months on endocrine therapy (ET) plus cyclin-dependent
kinase 4/6 inhibitor (CDK4/6i) in the LA/mBC setting, or recurrence while taking or
within 12 months of taking combination adjuvant ET plus CDK4/6i

- Documentation of the presence of a ESR1 mutation

General Exclusion Criteria:

- Previous enrollment in Roche- or Genentech-sponsored study of giredestrant

- Current participation in any ongoing Roche- or Genentech-sponsored clinical study of
giredestrant

- Eligible for participation in any ongoing Roche- or Genentech-sponsored clinical
study of giredestrant

- Inability to comply with EAP and follow-up procedures

- Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug
elimination half-lives (whichever is longer) prior to initiation of EAP treatment

- Treatment with any investigational therapy within 28 days prior to initiation of EAP
treatment

- Major surgery, chemotherapy, radiotherapy, or other anti-cancer therapy within 21
days prior to initiation of EAP treatment

- History of any other malignancy other than breast cancer within 3 years prior to
screening, except for appropriately treated carcinoma in situ of the cervix,
nonmelanoma skin carcinoma, papillary thyroid cancer treated with surgery, Stage I
endometrial cancer, or other non-breast cancers at very low risk of recurrence per
treating physician's judgment

- Known active uncontrolled or symptomatic central nervous system (CNS) metastases,
carcinomatous meningitis, or leptomeningeal disease. Participants with a history of
CNS metastases or cord compression are eligible if have been definitively treated
with local therapy (e.g., radiotherapy, surgery), are clinically stable, and have
not been treated with anticonvulsants or corticosteroids within 2 weeks prior to
initiation of EAP treatment

- Active cardiac disease or history of cardiac dysfunction

- Known clinically significant history of liver disease consistent with Child-Pugh
Class B or C, including active viral or other hepatitis (ex: hepatitis B [HBV] or
hepatitis C [HCV]) virus, current alcohol abuse or cirrhosis

- Interstitial lung disease or severe dyspnea at rest or requiring oxygen therapy

- Serious infection requiring oral or IV antibiotics, or other clinically significant
infection, within 14 days prior to initiation of EAP treatment

- Any serious medical condition or abnormality in clinical laboratory tests that, in
the treating physician's judgment, precludes the participant's safe participation in
and completion of the EAP

- Known allergy or hypersensitivity to any of the EAP drugs or any of their excipients

- Pregnant or breastfeeding, or intending to become pregnant during the EAP or within
the timeframe in which contraception is required

Exclusion Criteria for eBC Cohort:

- Current treatment or planned treatment with CDK4/6i as neoadjuvant or adjuvant
therapy. A short course of up to 12 weeks of neoadjuvant or adjuvant treatment with
CDK4/6i therapy prior to enrollment is allowed. A washout period of approximately 7
days is required between the last dose of CDK4/6i therapy and enrollment.

- History of >12 weeks of any endocrine treatment with selective ER modulator (e.g.,
tamoxifen), degrader, or aromatase inhibitor

Exclusion Criteria for LA/mBC Cohort:

- Progression on more than two prior lines of systemic ET in the locally advanced
unresectable or metastatic breast cancer setting

- Prior treatment with an oral selective estrogen receptor degrader (SERD),
proteolysis targeting chimera (PROTAC), complete estrogen receptor antagonist
(CERAN), novel oral selective estrogen receptor modulator (SERM), or everolimus in
any setting

- Advanced, symptomatic, visceral spread that is at risk of life-threatening
complications in the short term (including massive uncontrolled effusions [pleural,
pericardial, peritoneal] or pulmonary lymphangitis)

- Known positive HIV status and meeting any of the following criteria: CD4+ T-cell
count of <350 cells/uL; Detectable HIV viral load; History of an opportunistic
infection within the past 12 months; On stable antiretroviral therapy for <4 weeks

- Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major
upper gastrointestinal (GI) surgery including gastric resection, potentially
affecting enteral absorption, or a preexisting chronic condition resulting in
baseline Grade 2 or higher diarrhea