Overview
The study is a Phase 1b/2, multi-center, open-label, dose escalation trial evaluating the safety and preliminary efficacy of sapanisertib and serabelisib (PIKTOR) with fulvestrant and/or other anticancer therapies in participants with HR+/HER2- advanced/metastatic breast cancer.
Description
The study is a Phase 1b/2, multi-center, open-label, dose escalation trial evaluating the safety and preliminary efficacy of sapanisertib and serabelisib (PIKTOR) with fulvestrant and/or other anticancer therapies in participants with HR+/HER2- advanced/metastatic breast cancer.
Eligibility
Inclusion Criteria:
- Histologically confirmed diagnosis of HR+/HER2- breast cancer.
- Documented evidence of advanced or recurrent disease that is not amenable to surgery/radiation for curative intent.
- Participant has received at least one prior systemic therapy.
- At least 1 measurable or evaluable 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 triple-negative breast cancer.
- 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 breast 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.
- Gastric feeding tube (gastrostomy tube), gastrointestinal malabsorption, gastrointestinal anastomosis, bowel obstruction, or any other condition that might affect the absorption of study treatment.
- Significant cardiovascular impairment.
- Active, uncontrolled infection.
- Concurrent participation in another therapeutic clinical trial.
- Prior radiation therapy within 21 days prior to start of study treatment.
- Participants who have received a prior PI3K, AKT, mTORC1/2, or dual PI3K/mTOR inhibitor.
- 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.
- Prolongation of QTc interval to \>480 ms.
- Type 1 or Type 2 diabetes mellitus on insulin.