HR+ HER2- Breast Cancer
Conditions
Keywords
Serabelisib, Sapanisertib, Fulvestrant, Palbociclib, PI3K, mTOR, Dual PI3K/mTOR inhibition, Genetic Mutation, Faslodex, SERDs, Select Estrogen Receptor Degraders, CDK, CDK46, CDK4-6, HER2-, HER2 negative, HR+, HR positive, Hormone Receptor Positive, Advanced Breast Cancer, Metastatic Breast Cancer, Recurrent Breast Cancer, Breast Cancer, Cancer of the breast, Carcinoma of the breast, Neoplasms, Breast, Metabolism, Synthetic Lethality, Metabolism Programming, PIK3CA, Oral Medications, Antineoplastic agents, AKT
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.
Interventions
DRUGSerabelisib
Serabelisib is a selective, small molecule inhibitor of PI3Kα.
DRUGSapanisertib
Sapanisertib is a small molecule inhibitor of the mammalian mTOR serine/threonine kinase.
DRUGFulvestrant
Fulvestrant is a first-in-class SERD.
Sponsors
Faeth Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of drugs by assessment of adverse events (AEs) / serious adverse events (SAEs) | 2 years | Graded according to the National Cancer Institute (NCI CTCAE v5.0). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 2 years. | Defined as the proportion of participants from the Response-Evaluable population who have confirmed best overall response of either CR or PR according to RECIST v1.1 as confirmed by the Investigator. |
| Progression Free Survival (PFS) | Up to 5 years. | Defined as the time from first dose to the date of the first evidence of disease progression or death. |
| Progression Free Survival (PFS) at 6 months | 6 months | Defined as the progression free survival (PFS) rate at 6 months. |
| Overall Survival (OS) | Up to 5 years. | Defined as the time from first dose to the date of death due to any cause. |
| Clinical Benefit Rate (CBR) | Up to 5 years. | Defined as the percentage of participants from the All Treated population who achieve CR, PR, or SD. |
| Duration of Response (DoR) | Up to 5 years. | Defined for participants with a confirmed CR or PR as the time from response to the date of first evidence of disease progression or death. |
Countries
United States
Contacts
CONTACTMedical Monitor
Outcome results
None listed