Sapanisertib and Serabelisib (PIKTOR) With Paclitaxel and a Substudy With Diet in Patients With Advanced/Recurrent Endometrial Cancer

Inclusion Criteria

• Histologically confirmed diagnosis of endometrioid endometrial carcinoma.
• Documented evidence of advanced or recurrent endometrial cancer that is not amenable to surgery/radiation for curative intent.
• Participant has received at least 1 but not more than 3 prior systemic therapies. Prior therapy must include platinum-based chemotherapy and a checkpoint inhibitor, either separately or in combination.
• PI3K/AKT/mTOR pathway gene alteration identified.
• At least 1 measurable target lesion according to RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 at Screening.
• Non-pregnant, non-lactating females who are postmenopausal, surgically sterile or who agree to use effective contraceptive methods..

Exclusion Criteria

• Participants with central nervous system metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study
• Active malignancy (except for endometrial cancer, definitively treated in-situ carcinomas [e.g., breast, cervix, bladder], or basal or squamous cell carcinoma of the skin) within the past 24 months prior to treatment. Fully resected localized malignancies are eligible.
• Gastrointestinal malabsorption, gastrointestinal anastomosis, bowel obstruction, or any other condition that might affect the absorption of study treatment.
• Clinically significant hemoptysis or tumor bleeding.
• Significant cardiovascular impairment.
• Active, uncontrolled (requiring systemic antimicrobial therapy) infection.
• Concurrent participation in another therapeutic clinical trial.
• Prior radiation therapy within 21 days prior to start of study treatment.
• Strong CYP3A4 inhibitors, strong CYP1A2 inhibitors or CYP1A2 inducers, or clinically significant CYP3A4 inducers within 7 days before the first dose of study intervention, or participants who require treatment with strong CYP3A4 inhibitors or inducers during the study.
• Participants who require PPIs or chronic use of antacids, histamine H2 receptor blockers, or other treatments to raise gastric pH.
• Prolongation of QTc interval to >480 ms.
• HbA1c ≥ 8.0%, fasting serum glucose > 160 mg/dL, fasting triglycerides > 300 mg/dL or receiving treatment with insulin.