Sapanisertib and Serabelisib (PIKTOR) in Various Combinations in Patients With HR+/HER2- Advanced/Metastatic Breast Cancer

Purpose

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.

Condition

  • HR+ HER2- Breast Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible 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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort A1 - Sapanisertib and serabelisib (PIKTOR) with fulvestrant 		Subjects will receive doses of sapanisertib and serabelisib (PIKTOR) administered orally and fulvestrant administered intramuscularly.
  • Drug: Serabelisib
    Serabelisib is a selective, small molecule inhibitor of PI3Kα.
  • Drug: Sapanisertib
    Sapanisertib is a small molecule inhibitor of the mammalian mTOR serine/threonine kinase.
  • Drug: Fulvestrant
    Fulvestrant is a first-in-class SERD.
Experimental
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.
  • Drug: Serabelisib
    Serabelisib is a selective, small molecule inhibitor of PI3Kα.
  • Drug: Sapanisertib
    Sapanisertib is a small molecule inhibitor of the mammalian mTOR serine/threonine kinase.
  • Drug: Fulvestrant
    Fulvestrant is a first-in-class SERD.

Recruiting Locations

START Los Angeles
Los Angeles, California 90025

Oncology Associates of Oregon
Springfield, Oregon 97477

SCRI Oncology Partners
Nashville, Tennessee 37203

More Details

Status
Recruiting
Sponsor
Faeth Therapeutics

Study Contact

Medical Monitor
(708) 406-9282
clinicaltrials@faeththerapeutics.com

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.