Open-Label Umbrella Study to Evaluate Safety and Efficacy of Sapanisertib and Serabelisib (PIKTOR) in Various Combinations in Patients With HR+/HER2- Advanced or Metastatic Breast Cancer
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 32
- Locations
- 7
- Primary Endpoint
- Safety and tolerability of drugs by assessment of adverse events (AEs) / serious adverse events (SAEs)
Study Overview
Brief Summary
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.
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Cohort A1 - Sapanisertib and serabelisib (PIKTOR) with fulvestrant
Subjects will receive doses of sapanisertib and serabelisib (PIKTOR) administered orally and fulvestrant administered intramuscularly.
Intervention: Serabelisib (Drug)
Cohort A1 - Sapanisertib and serabelisib (PIKTOR) with fulvestrant
Subjects will receive doses of sapanisertib and serabelisib (PIKTOR) administered orally and fulvestrant administered intramuscularly.
Intervention: Fulvestrant (Drug)
Cohort A1 - Sapanisertib and serabelisib (PIKTOR) with fulvestrant
Subjects will receive doses of sapanisertib and serabelisib (PIKTOR) administered orally and fulvestrant administered intramuscularly.
Intervention: Sapanisertib (Drug)
Cohort A2 - Sapanisertib and serabelisib (PIKTOR) with fulvestrant
Subjects will receive doses of sapanisertib and serabelisib (PIKTOR) at a higher dose than Cohort A1 administered orally and fulvestrant administered intramuscularly.
Intervention: Fulvestrant (Drug)
Cohort A2 - Sapanisertib and serabelisib (PIKTOR) with fulvestrant
Subjects will receive doses of sapanisertib and serabelisib (PIKTOR) at a higher dose than Cohort A1 administered orally and fulvestrant administered intramuscularly.
Intervention: Serabelisib (Drug)
Cohort A2 - Sapanisertib and serabelisib (PIKTOR) with fulvestrant
Subjects will receive doses of sapanisertib and serabelisib (PIKTOR) at a higher dose than Cohort A1 administered orally and fulvestrant administered intramuscularly.
Intervention: Sapanisertib (Drug)
Outcomes
Primary Outcomes
Safety and tolerability of drugs by assessment of adverse events (AEs) / serious adverse events (SAEs)
Time Frame: 2 years
Graded according to the National Cancer Institute (NCI CTCAE v5.0).
Secondary Outcomes
- Objective Response Rate (ORR)(Up to 2 years.)
- Progression Free Survival (PFS)(Up to 5 years.)
- Progression Free Survival (PFS) at 6 months(6 months)
- Overall Survival (OS)(Up to 5 years.)
- Clinical Benefit Rate (CBR)(Up to 5 years.)
- Duration of Response (DoR)(Up to 5 years.)