Breast Cancer
Conditions
Keywords
Breast Cancer, Advanced or Metastatic, Gedatolisib, HR Positive, ER Positive, HER2 Negative, PIK3CA MT, PI3K
Brief summary
This is a Phase 3, open-label, randomized, clinical trial evaluating the efficacy and safety of gedatolisib and palbociclib plus endocrine therapy for the treatment of patients with locally advanced or metastatic HR+/HER2- advanced breast cancer.
Detailed description
This is a Phase 3, open-label, randomized clinical trial evaluating the efficacy and safety of gedatolisib plus endocrine therapy and palbociclib versus endocrine therapy and ribociclib for the treatment of patients with advanced (inoperable) or metastatic hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer. Following completion of the screening procedures to determine eligibility, patients will be assigned manually according to their endocrine sensitivity status to either Study 1 (endocrine-resistant) or Study 2 (endocrine-sensitive) and subsequently be randomized 1:1 to either investigational treatment or standard-of-care control. Study 1 is expected to enroll approximately 440 subjects with treatment-naïve endocrine-resistant ABC whose cancer progressed while receiving or within 12 months of completing adjuvant endocrine therapy. The trial will evaluate the efficacy and safety of the investigational arm (gedatolisib combined with palbociclib and fulvestrant - Arm A) compared to the control arm (ribociclib combined with fulvestrant - Arm B). Study 2 is expected to enroll approximately 740 subjects with treatment-naïve endocrine-sensitive ABC whose cancer relapsed or progressed 12 months or more after completion of adjuvant endocrine therapy, or those with de novo metastatic disease without prior endocrine therapy exposure. The trial will evaluate the efficacy and safety of the investigational arm (gedatolisib combined with palbociclib and letrozole - Arm C) compared to the control arm (ribociclib combined with letrozole - Arm D). Gedatolisib is an intravenously administered pan-PI3K/mTOR inhibitor. Palbociclib and ribociclib are CDK4/6 inhibitors. Fulvestrant is a selective estrogen receptor degrader (SERD). Letrozole is an aromatase inhibitor (AI).
Interventions
DRUGArm A: Gedatolisib + Palbociclib + Fulvestrant
Drug: Gedatolisib Participants will receive intravenous (IV) gedatolisib once weekly for 3 weeks (Days 1, 8, 15) followed by 1 week off Other Names: • PF-05212384 Drug: Palbociclib Participants will receive oral palbociclib on days 1-21 of each 28-day cycle. Other Names: • IBRANCE Drug: Fulvestrant Participants will receive intramuscular (IM) fulvestrant every 2 weeks during Cycle 1 and then every 4 weeks Other Names: • Faslodex
DRUGArm B: Ribociclib + Fulvestrant
Drug: Ribociclib Participants will receive oral ribociclib on Days 1-21 of each 28-day cycle Other Names: • KISQALI® Drug: Fulvestrant Participants will receive intramuscular (IM) fulvestrant approximately every 2 weeks during Cycle 1 then approximately every 4 weeks Other Names: • Faslodex
DRUGArm C: Gedatolisib + Palbociclib + Letrozole
Drug: Gedatolisib Participants will receive intravenous (IV) gedatolisib once weekly for 3 weeks (Days 1, 8, 15) followed by 1 week off Drug: Palbociclib Participants will receive oral palbociclib on days 1-21 of each 28-day cycle. Drug: Letrozole Participants will receive oral letrozole daily.
DRUGArm D: Ribociclib + Letrozole
Drug: Ribociclib Participants will receive oral ribociclib on Days 1-21 of each 28-day cycle Drug: Letrozole Participants will receive oral letrozole daily.
Sponsors
Celcuity Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed diagnosis of metastatic or locally advanced HR+/HER2- breast cancer 2. Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with an LHRH agonist. Patients are to have commenced concomitant treatment with LHRH agonist prior to or on Cycle 1, Day 1 and must be willing to continue for the duration of the study. 3. Negative pregnancy test for females of childbearing potential. Female subjects who are not surgically sterile must use a medically effective contraceptive method from screening until 2 years after the last dose of study treatment. 4. Progression of disease during or within 12 months of completing (neo)adjuvant endocrine therapy (ET) or progression of disease after 12 months of completing (neo)adjuvant ET. 5. Adequate archival, fresh tumor tissue, or liquid biopsy for the analysis of PIK3CA mutational status. 6. Permitted prior therapies: 1. (neo)adjuvant fulvestrant only if the treatment duration \< 6 months 2. (neo)adjuvant chemotherapy 3. (neo)adjuvant CDK4/6 inhibitor, unless PD was on or within 6 months of discontinuation of CDK4/6i i. Study 1: if disease progression was on or within event occurred \>6 months of discontinuation after completion of CDK4/6 inhibitor portion of treatment. ii. Study 2: if disease progression event occurred \>12 months after completion of CDK4/6 inhibitor portion of treatment. 7. Subject has radiologically measurable disease according to RECIST v1.1, per local assessment. Patients with nonmeasurable bone-only disease are not eligible. Patients with bone-only disease that has lytic or mixed lytic/blastic lesions and at least one measurable soft tissue component per RECIST v1.1 may be eligible. 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 9. Life expectancy of at least \>6 months. 10. Adequate bone marrow, hepatic, renal and coagulation function.
Exclusion criteria
1. Concurrent malignancies other than adequately treated non-melanoma skin cancer. Previous malignancies in remission but curatively treated with no evidence of disease progression and judged by local Investigator to be at low risk of impacting health or survival while on study. 2. Prior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor, a protein kinase B (Akt) inhibitor, or a mechanistic target of rapamycin (mTOR) inhibitor or any other selective estrogen receptor degrader (SERD), except fulvestrant, used in (neo)adjuvant setting. 3. Prior treatment with systemic anticancer therapy for ABC 4. Subjects with type 1 diabetes, or uncontrolled type 2 diabetes requiring daily insulin therapy. 5. Known and untreated, or active, brain or leptomeningeal metastases 6. History of clinically significant cardiovascular abnormalities 7. Known, clinically significant ophthalmic conditions 8. History of drug-induced symptomatic interstitial lung disease (pneumonitis) or hepatitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From date of randomization to the date of death due to any cause, up to approximately 48 months | PFS is defined as the time from randomization to death or the first documented progression, whichever occurs first, confirmed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, as determined based on blinded independent central review (BICR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From date of randomization to the date of death due to any cause, up to approximately 48 months | OS is defined as the length of time from randomization until the date of death from any cause method, where PFS is defined as the time from randomization to death or the first documented progression, whichever occurs first, confirmed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, as determined based on blinded independent central review (BICR) |
| Overall Response Rate (ORR) | Up to approximately 48 months | Percentage of subjects who achieved an objective response according to RECIST v1.1 criteria (complete response \[CR\] or partial response \[PR\]) as assessed by BICR) |
| Duration of Response (DOR) | Up to approximately 48 months | Time from the assessment of initial response (PR or better) to death or first documented radiologically confirmed disease progression as assessed by BICR, whichever occurs first |
| Time to Response (TTR) | Time from randomization to the first assessment of PR or better as assessed by BICR | Time to Response (TTR) |
| Clinical Benefit Rate (CBR) | Up to approximately 48 months | Percentage of subjects with CR or PR; or with stable disease (SD) lasting \>24 weeks as assessed by BICR |
| Quality of Life (QOL) Functional Assessment of Cancer Therapy - Breast Trial Outcome Index (FACT-B TOI) | From baseline to 30 Day Safety Follow-up | — |
| Adverse Events | Up to approximately 48 months | Type, incidence, severity (as graded by the NCI CTCAE v5.0), seriousness, and relationship to study medications of Adverse Events and any laboratory abnormalities |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Czechia, France, Germany, Greece, Hungary, Italy, Malaysia, Mexico, Poland, Portugal, Romania, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United States
Contacts
CONTACTNadene Zack, MS
Outcome results
None listed