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

Eligibility 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..
• * 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.