Phase 3 Study of Gedatolisib as First-Line Treatment for Patients With HR-Positive, HER2-Negative Advanced Breast Cancer (VIKTORIA-2)

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of metastatic or locallyadvanced HR+/HER2- breast cancer

2. Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (andperi-menopausal) women can be enrolled if amenable to treatment with an LHRHagonist. Patients are to have commenced concomitant treatment with LHRH agonistprior to or on Cycle 1, Day 1 and must be willing to continue for the duration ofthe study.

3. Negative pregnancy test for females of childbearing potential. Female subjects whoare not surgically sterile must use a medically effective contraceptive method fromscreening until 2 years after the last dose of study treatment.

4. Progression of disease during or within 12 months of completing (neo)adjuvant ET.

5. Adequate archival, fresh tumor tissue, or liquid biopsy for the analysis of PIK3CAmutational status.

6. Permitted prior therapies:

7. (neo)adjuvant fulvestrant or any selective ER degrader only if the treatmentduration < 6 months

8. (neo)adjuvant chemotherapy

9. (neo)adjuvant CDK4/6 inhibitor, unless PD was on or within 6 months ofdiscontinuation of CDK4/6i

10. Subject has radiologically measurable disease according to RECIST v1.1, per localassessment. Patients with evaluable bone-only disease are not eligible. Patientswith bone-only disease that has lytic or mixed lytic/blastic lesions and at leastone measurable soft tissue component per RECIST v1.1 may be eligible.

11. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

12. Life expectancy of at least >6 months.

13. Adequate bone marrow, hepatic, renal and coagulation function.

Exclusion Criteria:

1. Concurrent malignancies other than adequately treated non-melanoma skin cancer.Previous malignancies in remission but curatively treated with no evidence ofdisease progression and judged by local Investigator to be at low risk of impactinghealth or survival while on study.

2. Prior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor, a protein kinaseB (Akt) inhibitor, or a mechanistic target of rapamycin (mTOR) inhibitor

3. Prior treatment with systemic anticancer therapy for ABC

4. Subjects with type 1 diabetes

5. Known and untreated, or active, brain or leptomeningeal metastases

6. History of clinically significant cardiovascular abnormalities

7. History of drug-induced symptomatic interstitial lung disease (pneumonitis) orhepatitis