Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as PF-05212384, PKI-587
Gedatolisib · 6 trials · 9 indications
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)
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)
Number of patients alive and disease progression-free per RECIST 1.1 criteria.
Number of patients who experience objective tumor responses per RECIST 1.1 criteria.
Type, incidence, severity (as graded by National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0), seriousness, and relationship to study medications of adverse events (AEs) and any laboratory abnormalities
Incidence of dose-limiting toxicities (DLTs) and AEs graded according to NCI CTCAE v5.0
Radiographic progression-free survival rate at 6 months as measured by the Kaplan-Meier (K-M) method and assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 with modifications as specified in Prostate Cancer Working Group 3 (PCWG3) criteria
Determine the recommended Phase 2 dose (RP2D) of talazoparib in combination with gedatolisib in patients with advanced human epidermal growth factor receptor 2 (HER2) negative (triple negative or BRCA1/2 deficient) breast cancer.
Calculate ORR, which will include confirmed complete response (CR) + confirmed partial response (PR) determined as per RECIST1.1 on treatment with talazoparib in combination with gedatolisib in patients with BRCA1/2 deficient advanced HER2 negative breast cancer.
Number of patients for each response category, objective response rate (number of patients with a complete response (CR)) relative to the number of response evaluable patients
| Arm | Type | Description |
|---|---|---|
| Arm A: Gedatolisib + Palbociclib + Fulvestrant | EXPERIMENTAL | Subjects with treatment-naïve endocrine-resistant ABC. |
| Arm B: Ribociclib + Fulvestrant | ACTIVE_COMPARATOR | Subjects with treatment-naïve endocrine-resistant ABC. |
| Arm C: Gedatolisib + Palbociclib + Letrozole | EXPERIMENTAL | Subjects with treatment-naïve endocrine-sensitive ABC. |
| Arm D: Ribociclib + Letrozole | ACTIVE_COMPARATOR | Subjects with treatment-naïve endocrine-sensitive ABC. |
| Arm A - Patients Lacking PIK3CA Mutations (WT) | EXPERIMENTAL | Gedatolisib + Palbociclib + Fulvestrant |
| Arm B - Patients Lacking PIK3CA Mutations (WT) | EXPERIMENTAL | Gedatolisib + Fulvestrant |
| Arm C - Patients Lacking PIK3CA Mutations (WT) | ACTIVE_COMPARATOR | Fulvestrant |
| Arm D - Patients with PIK3CA Mutation (MT) | EXPERIMENTAL | Gedatolisib + Palbociclib + Fulvestrant |
| Arm E - Patients with PIK3CA Mutation (MT) | ACTIVE_COMPARATOR | Alpelisib + Fulvestrant |
| Arm F - Patients with PIK3CA Mutation (MT) | EXPERIMENTAL | Gedatolisib + Fulvestrant |
| Cohort 1 | EXPERIMENTAL | * Abemaciclib is administered by mouth twice daily * LY3023414 is administered by mouth twice daily * Letrozole is administered by mouth once daily |
| Cohort 2 | EXPERIMENTAL | * Abemaciclib is administered by mouth twice daily * LY3023414 is administered by mouth twice daily |
| Cohort 1A | EXPERIMENTAL | * Abemaciclib is administered by mouth twice daily * Letrozole is administered by mouth once daily |
| Cohort 3 | EXPERIMENTAL | * Abemaciclib is administered by mouth twice daily * Letrozole is administered by mouth once daily * Metformin is administered by mouth once daily |
| Cohort 6 | EXPERIMENTAL | * Abemaciclib is administered by mouth twice daily * Letrozole is administered by mouth once daily * Gedatolisib is administered intravenously on days 1, 8 and 15 of a 28-day cycle |
| Cohort 7 | EXPERIMENTAL | * Abemaciclib is administered by mouth twice daily * Letrozole is administered by mouth once daily * Gedatolisib is administered intravenously on days 1, 8 and 15 of a 28-day cycle |
| Phase 1 Arm 1 | EXPERIMENTAL | Arm 1 - 120 mg of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle) |
| Phase 1 Arm 2 | EXPERIMENTAL | Arm 2 - 180 mg of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle) |
| Phase 2 | EXPERIMENTAL | The recommended Phase 2 dose (RP2D) of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle) |
| Talazoparib + Gedatolisib | EXPERIMENTAL | Talazoparib + Gedatolisib Phase 1: Dose Level -1: Gedatolisib 150mg IV, Days 1,8,15,22; Talazoparib 0.75 mg/orally qd, Days 1-28 Dose Level 1: Gedatolisib 180mg IV, Days 1,8,15,22; Talazoparib 0.75 mg/orally qd, Days 1-28 Dose Level 2: Gedatolisib 180mg IV, Days 1,8,15,22; Talazoparib 1.00 mg/orally qd, Days 1-28 Phase 2: Gedatolisib 180 mg IV on days 1, 8, 15 and 22; Talazoparib 1.00 mg once daily, Days 1-28. Subjects receiving weekly gedatolisib may continue current regimen or may switch to gedatolisib 180 mg IV on days 1, 8, and 15; Talazoparib 1.00 mg once daily, Days 1-28 (3 weeks on/ 1 week off). All changes will be permanent. |
| Letrozole Cohort | EXPERIMENTAL | Letrozole combination cohort in dose escalation |
| Fulvestrant cohort | EXPERIMENTAL | Fulvestrant combination cohort in dose escalation |
| ARM A | EXPERIMENTAL | Gedatolisib + palbociclib + letrozole in dose expansion |
| ARM B | EXPERIMENTAL | Gedatolisib + palbociclib + fulvestrant in dose expansion |
| ARM C | EXPERIMENTAL | Gedatolisib + palbociclib + fulvestrant in dose expansion |
| Arm D | EXPERIMENTAL | Gedatolisib (3:1) + palbociclib + fulvestrant in dose expansion |
| Name | Type | Description |
|---|---|---|
| Arm A: Gedatolisib + Palbociclib + Fulvestrant | DRUG | 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 |
| Arm B: Ribociclib + Fulvestrant | DRUG | 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 |
| Arm C: Gedatolisib + Palbociclib + Letrozole | DRUG | 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. |
| Arm D: Ribociclib + Letrozole | DRUG | Drug: Ribociclib Participants will receive oral ribociclib on Days 1-21 of each 28-day cycle Drug: Letrozole Participants will receive oral letrozole daily. |
| Gedatolisib | DRUG | Gedatolisib 180 mg IV given weekly for 3 weeks (Days 1, 8, 15) followed by 1 week off |
| Palbociclib | DRUG | Palbociclib 125 mg PO given daily for 3 weeks (21 days), followed by 1 week off |
| Fulvestrant | DRUG | Fulvestrant 500 mg IM (2 × 5 mL injections) given every 2 weeks during Cycle 1 (Days 1 and 15), then every 4 weeks beginning with Cycle 2 Day 1 |
| Alpelisib | DRUG | Alpelisib 300 mg PO (2 × 150 mg tablets) given daily for 4 weeks (28 days) |
| Letrozole | DRUG | Letrozole is a hormonal therapy that works by lowering the production of estrogen in the body. |
| Abemaciclib | DRUG | Abemaciclib is a cyclin-dependent kinase (CDK) inhibitor. |
| LY3023414 | DRUG | LY3023414 is a potent selective inhibitor of the class I PI3K isoforms, mTOR, and DNA-PK. |
| Metformin | DRUG | Metformin inhibits mitochondrial adenosine-5'-triphosphate (ATP) synthesis, resulting in activation of the AMPK (5' AMP-activated protein kinase) pathway through LKB1, eventually causing inhibition of the mTOR pathway and subsequent reduction in protein synthesis and cellular proliferation. |
| Darolutamide | DRUG | Darolutamide is a novel androgen receptor inhibitor that has been studied and received approval for treatment of patients with nonmetastatic CRPC and in metastatic hormone-sensitive prostate cancer. |
| Talazoparib | DRUG | .75-1.00mg |
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 agoni...
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Gedatolisib is an investigational small molecule being studied in breast cancer, endometrial cancer, triple-negative breast cancer, and metastatic castration-resistant prostate cancer. It is being developed as a treatment for advanced or metastatic solid tumors, with the most advanced clinical program in HR-positive, HER2-negative advanced breast cancer.
Gedatolisib is a pan-PI3K inhibitor that targets the PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, and PIK3R2 subunits of phosphoinositide 3-kinase. By inhibiting these targets, it is designed to block the PI3K signaling pathway, which is frequently dysregulated in breast cancer and other solid tumors.
Gedatolisib is being developed by Celcuity Inc., a biopharmaceutical company traded on the Nasdaq under the ticker CELC. Celcuity is the sponsor of the clinical trials evaluating gedatolisib in breast cancer and prostate cancer.
Gedatolisib is in Phase 3 clinical development. The Phase 3 program includes the VIKTORIA-1 and VIKTORIA-2 trials in HR-positive, HER2-negative advanced breast cancer. Gedatolisib has received a Priority Review designation from the FDA, but it remains an investigational drug and is not approved for any indication.
Gedatolisib is being evaluated in several clinical trials. The Phase 3 VIKTORIA-2 trial (NCT06757634) is testing gedatolisib as first-line treatment for HR-positive, HER2-negative advanced breast cancer. The Phase 3 VIKTORIA-1 trial (NCT05501886) is studying gedatolisib plus fulvestrant with or without palbociclib in advanced breast cancer. A Phase 1 trial (NCT06190899) is testing gedatolisib with darolutamide in metastatic castration-resistant prostate cancer, and another Phase 1 trial (NCT03911973) is evaluating gedatolisib plus talazoparib in triple-negative breast cancer.