Udvidet adgangsprogram til tilvejebringelse af Giredestrant til deltagere med ER+, HER2- tidlig eller lokalt fremskreden/metastatisk brystkræft

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