LidERA

The inclusion criteria includes the following:

- Participants who are capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form and in this protocol.

- Participants (females, regardless of menopausal status, and males) who are age ≥ 18 years at the time of signing the Informed Consent Form.

- Participants who have documented ER+ tumor by immunohistochemistry, as assessed locally on a primary disease specimen and defined as ≥ 1% of tumor cells stained positive according to the ASCO/College of American Pathologists (CAP) guidelines.

- Participants who have documented HER2- tumor, as assessed locally on a primary disease specimen and defined according to ASCO/CAP guidelines.

- Participants who have multicentric (the presence of two of more tumor foci within different quadrants of the same breast) and/or multifocal (the presence of two or more tumor foci within a single quadrant of the breast) breast cancer are also eligible if all examined tumors meet pathologic criteria for ER positivity and HER2 negativity.

- Participants must have undergone definitive surgery of the primary breast tumor(s)with some exceptions allowed.

- Participants who received or will be receiving adjuvant chemotherapy must have completed adjuvant chemotherapy prior to randomization.

- Participants for whom resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE v5.0 Grade 1 or better (except alopecia, Grade < 2 peripheral neuropathy, arthralgia, or other toxicities not considered a safety risk for the participant per the investigator’s judgment).

- Participants have received (neo)adjuvant chemotherapy and/or had surgery and had no prior endocrine therapy are eligible, provided that they are enrolled within 12 months following definitive breast cancer surgery.

- Participants who have confirmed availability of an untreated primary breast tumor tissue specimen suitable for biomarker testing (i.e., representative archived formalin-fixed, paraffin-embedded [FFPE] tissue block [preferred] or 15-20 slides containing unstained, freshly cut, serial sections), with associated de-identified pathology report is required.

- Participants who received neoadjuvant chemotherapy must have residual disease in lymph nodes (≥ ypN1) after neoadjuvant chemotherapy and will be stratified to medium or high risk, based on disease characteristics.

- Participants with T4 primary tumor and any N.

- Participant who have Eastern Cooperative Oncology Group Performance (ECOG) Performance Status 0, 1, or 2.

- Participants who are able and willing to swallow, retain, and absorb oral medication.

- Participants who have adequate organ function.

- For women of childbearing potential: participants who agree to remain abstinent or use contraception.

- For men assigned: participants who agree to remain abstinent or use a condom, and agree to refrain from donating sperm. 

The exclusion criteria includes the following;

- Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 9 days after the final dose of giredestrant, or within the time period specified per local prescribing guidelines after the final dose of TPC.

- Participants who have received treatment with investigational therapy within 28 days prior to initiation of study treatment or is currently enrolled in any other type of medical research judged by the Sponsor not to be scientifically or medically compatible with this study.

- Participants receiving or planning to receive a CDK4/6i as adjuvant therapy.

- Participants who have active cardiac disease or history of cardiac dysfunction.

- Participants who have been diagnosed with Stage IV breast cancer.

- Participants who have a history of any prior (ipsilateral and/or contralateral) invasive breast cancer or DCIS. Participants with a history of contralateral DCIS treated by only local regional therapy at any time may be eligible.

- Participants who have a history of any other malignancy within 3 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer.

- Participants who have had any prior endocrine treatment with selective ER downregulators, degraders, or AI.

- Participants who have clinically significant liver disease consistent with Child-Pugh Class B or C, including active hepatitis (e.g., hepatitis B virus [HBV] or hepatitis C virus [HCV]), current alcohol abuse, cirrhosis, or positive test for viral hepatitis.

- Participants who have a known allergy or hypersensitivity to any of the study drugs or any of their excipients.

- Pre- and perimenopausal participants or male participants who have a known hypersensitivity to LHRH agonists.

- Participants who have a documented history of haemorrhagic diathesis, coagulopathy, or thromboembolism.

- Participants who have had a major surgical procedure unrelated to breast cancer within 28 days prior to randomization.

- Participants who have had a serious infection requiring oral or IV antibiotics within 14 days prior to screening or other clinically significant infection (e.g., COVID-19) within 14 days prior to screening.

- Participants who have had any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes an individual's safe participation in and completion of the study.

- Participants who are unable or unwilling to comply with the requirements of the protocol in the opinion of the investigator. 

Research Nurse: Huang Haiyan (Nolly) (x3766) Haiyan.Huang@lthtr.nhs.uk

Administrator: Rob Speirs (x8475)