A Phase IIIb Study to Evaluate Camizestrant Plus Ribociclib in ER-positive, HER2-negative Advanced Breast Cancer

Inclusion Criteria: 1. Capable of giving signed informed consent. 2. Female or male, must be ≥ 18 years or as per locally allowed age limit for screening. Type of Participant and Disease Characteristics 3. Histologically or cytologically documented diagnosis of ER+, HER2- BC based on local laboratory results and who are not amenable to resection or radiation therapy with curative intent. 4. Previously untreated with any systemic anti-cancer therapy for their locoregionally recurrent or metastatic ER+ disease. 5. De novo Stage 4 disease, or recurrence from early CD stage breast cancer after having received standard adjuvant endocrine therapy. Note that at least 12 months must have elapsed since the patient's last dose of adjuvant AI therapy without disease progression on treatment. Note that a 2-week washout period is required after the last dose of tamoxifen prior to randomisation. 6. ECOG performance status of 0 or 1. 7. Adequate organ and marrow function. Sex and Contraceptive/Barrier Requirements 8. For those female or male patients who are not abstinent (in line with their preferred and usual lifestyle choice), and intend to be heterosexually active with a partner: Female patients must be using highly effective contraceptive measures from the time of screening until 4 weeks after discontinuation of study treatment, and must have a negative serum pregnancy test before first dose of any study treatment if they are of childbearing potential; or must have evidence of nonchild-bearing potential by fulfilling one of the following criteria at screening: (a) Post-menopausal, defined as women with cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause: (i) Age ≥ 60 years (ii) Age \< 60 years with serum estradiol and FSH level within the laboratory's reference range for post-menopausal females (iii) Previous bilateral surgical oophorectomy (iv) Medically confirmed ovarian failure OR (b) Pre/peri-menopausal, ie, not meeting the criteria for being post-menopausal. (i) Pre-/peri-menopausal women can be enrolled if amenable to be treated with monthly LHRH agonists (goserelin or leuprorelin \[also known as leuprolide\]). Patients must have concomitant treatment with LHRH agonists (goserelin or leuprorelin \[leuprolide\]) before or on the same day as the first dose of study treatment - and must be willing to continue on it for the duration of the study. Non sterilised male partners of a patient who is a woman of childbearing potential must use a male condom plus spermicide (condom alone in countries where spermicides are not approved) throughout this period. Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception from the time of screening throughout the total duration of the programme and the drug washout period to prevent pregnancy in a partner. Male participants must not donate or bank sperm during this same time period. Male patients can be enrolled if amenable to be treated with monthly LHRH agonists (goserelin or leuprorelin \[also known as leuprolide\]) unless the patients have clear orchiectomy medical history. Willingness to use 2 non-hormonal based methods of contraception throughout the study. Exclusion Criteria: 1. Participants who are not clinically indicated for endocrine therapy in combination with the CDK4/6 inhibitor ribociclib. 2. No evidence of advanced inoperable disease, or bone only disease with sclerotic/osteoblastic bone lesions only per standard of care imaging. 3. Have advanced, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term, and/or pulmonary lymphangitis. 4. Persistent treatment-induced non-haematological toxicities (CTCAE Grade \> 2). 5. Known active infection including tuberculosis HBV and HCV. 6. Known to have tested positive for HIV. Participants with HIV may be enrolled if they fulfil the criteria recommended by FDA and ASCO guidelines. 7. Any clinically important abnormalities in heart conduction patterns; participants with pacemakers or medically controlled atrial fibrillation are not excluded. 8. Ongoing symptomatic hypotension. 9. Pregnant or lactating women or patients not willing to use highly effective contraception as defined in the protocol.