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 amenableto 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 orwho agree to use effective contraceptive methods..

Exclusion Criteria:

• Participants with central nervous system metastases are not eligible, unless theyhave completed local therapy and have discontinued the use of corticosteroids forthis indication for at least 4 weeks before starting treatment in this study

• Active malignancy (except for endometrial cancer, definitively treated in-situcarcinomas [e.g., breast, cervix, bladder], or basal or squamous cell carcinoma ofthe skin) within the past 24 months prior to treatment. Fully resected localizedmalignancies are eligible.

• Gastrointestinal malabsorption, gastrointestinal anastomosis, bowel obstruction, orany 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 clinicallysignificant CYP3A4 inducers within 7 days before the first dose of studyintervention, or participants who require treatment with strong CYP3A4 inhibitors orinducers during the study.

• Participants who require PPIs or chronic use of antacids, histamine H2 receptorblockers, 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/dLor receiving treatment with insulin.