Combining sapanisertib and serabelisib (PIKTOR) with hormonal therapy for HR+/HER2- advanced breast cancer

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

Phase1; Phase2 Interventional Faeth Therapeutics · NCT07558733

This trial will test whether combining sapanisertib and serabelisib (PIKTOR) with fulvestrant and other therapies can help people with HR+, HER2- advanced or metastatic breast cancer.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment32 (estimated)
Ages18 Years and up
SexAll
SponsorFaeth Therapeutics Industry-sponsored
Drugs / interventionsradiation
Locations3 sites (Los Angeles, California and 2 other locations)
Trial IDNCT07558733 on ClinicalTrials.gov

What this trial studies

This is a Phase 1b/2, multi-center, open-label, dose-escalation trial that gives sapanisertib and serabelisib (PIKTOR) alone or together with fulvestrant and other anticancer therapies to participants with HR+/HER2- advanced or metastatic breast cancer. The Phase 1b portion determines safe dose levels and the Phase 2 portion gathers preliminary evidence of anti-tumor activity. Eligible participants must have measurable disease per RECIST v1.1, an ECOG performance status of 0–1, and prior systemic therapy for advanced disease, while uncontrolled CNS metastases and certain active malignancies are excluded.

Who should consider this trial

Good fit: Adults with histologically confirmed HR+, HER2- advanced or metastatic breast cancer who have received at least one prior systemic therapy, have measurable disease, an ECOG 0–1, and are postmenopausal or using effective contraception are ideal candidates.

Not a fit: Patients with triple-negative breast cancer, uncontrolled or active CNS metastases, poor performance status (ECOG >1), pregnant or breastfeeding women, or those unable to tolerate the study drugs are unlikely to benefit.

Why it matters

Potential benefit: If successful, this combination could delay disease progression and help overcome resistance to endocrine therapy in HR+/HER2- advanced breast cancer.

How similar studies have performed: Other drugs targeting the PI3K/mTOR pathway (for example alpelisib and everolimus) have shown benefit in endocrine-resistant HR+ breast cancer, but the specific sapanisertib + serabelisib combination is experimental with limited prior clinical data.

Eligibility criteria

Show full inclusion / exclusion criteria
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.

Where this trial is running

Los Angeles, California and 2 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions HR+ HER2- Breast CancerSerabelisibSapanisertibFulvestrantPalbociclibPI3KmTORDual PI3K/mTOR inhibition
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.