Sapanisertib and Serabelisib (PIKTOR) With Paclitaxel and a Substudy With an Insulin-Suppressing 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 4 prior systemic therapies.Prior therapy must include platinum-based chemotherapy and a checkpoint inhibitor,either separately or in combination. If a subject has been unable to be treated withcheckpoint inhibitor in the past due to medical contraindications, consult withMedical Monitor.

• 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.

• Gastric feeding tube (gastrostomy tube), gastrointestinal malabsorption,gastrointestinal anastomosis, bowel obstruction, or any other condition that mightaffect the absorption of study treatment.

• Clinically significant (per Investigator judgement) 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 and inducers are prohibited during the study. Strong CYP1A2inhibitors as well as CYP1A2 inducers should be administered with caution and at thediscretion of the Investigator. Alternative treatments, if available, should beconsidered. Additionally, strong CYP3A4 inhibitors or inducers should not be takenwithin 7 days before the first dose of study intervention.

• 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% or fasting serum glucose > 160 mg/dL or fasting triglycerides > 300mg/dL or receiving treatment with insulin.