Gedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or Metastatic HR+/HER2- Breast Cancer (VIKTORIA-1) (VIKTORIA-1)

• ClinicalTrials.gov Identifier: NCT05501886
• Recruitment Status: Recruiting
• First Posted: August 16, 2022
• Last Update Posted: August 1, 2023
• Sponsor: Celcuity Inc
• Information provided by (Responsible Party): Celcuity Inc

Tracking Information

• First Submitted Date: August 12, 2022
• First Posted Date: August 16, 2022
• Last Update Posted Date: August 1, 2023
• Actual Study Start Date: September 30, 2022
• Estimated Primary Completion Date: September 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 12, 2022)

Progression Free Survival (PFS) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer [ Time Frame: 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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 12, 2022)

• Overall Survival (OS) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer [ Time Frame: 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) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer [ Time Frame: 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) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer [ Time Frame: Up to approximately 48 months ]
  Time from the assessment of initial response (PR or better) to death or first documented disease progression as assessed by BICR, whichever occurs first
• Time to Response (TTR) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer [ Time Frame: Up to approximately 48 months ]
  Time form randomization to the first assessment of PR or better as assessed by BICR, whichever comes first
• Clinical Benefit Rate (CBR) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer [ Time Frame: Up to approximately 48 months ]
  Percentage of subjects with CR, PR, or stable disease (SD) >24 weeks as assessed by BICR
• Quality of Life (QOL)Functional Assessment of Cancer Therapy - Breast Trial Outcome Index (FACT-B TOI) Questions in Patients with PIK3CA WT and PIK3CA MT Breast Cancer [ Time Frame: From baseline to 30 Day Safety Follow-up ]
  The FACT-B TOI is an abbreviated (24-item) version of the full FACT-B which focuses only on the patient's Physical Well-being (PWB), Functional Well-being (FWB), and Breast Cancer Subscale (BCS) components using a 5-level scale, (Not at all, A little bit, Some-what, Quite a bit, Very much).
• Quality of Life (QOL) NCCN-FACT Breast Symptom Index -16 (NFBSI-16) in Patients with PIK3CA WT and PIK3CA MT Breast Cancer [ Time Frame: From baseline to 30 Day Safety Follow-up ]
  NCCN-FACT is derived from the FACT-B and only 4 additional items will be administered to enable optional scoring of the NFBSI subscales and total score using a 5-level scale (Not at all, A little bit, Some-what, Quite a bit, Very much).
• Patient-Reported Outcomes in Patients with PIK3CA WT and PIK3CA MT Breast Cancer [ Time Frame: From baseline to 30 Day Safety Follow-up ]
  Patient-Reported Outcomes Measurement Information System (PROMIS®) Short Form v2.0 - Physical Function 8c using a 5-level scale (Without any difficulty, With a little difficulty, With some difficulty, With much difficulty, Unable to do)
• EuroQol 5 in Patients with PIK3CA WT and PIK3CA MT Breast Cancer [ Time Frame: From baseline to 30 Day Safety Follow-up ]
  EuroQol 5 Dimension 5 Level (EQ-5D-5L) - This is a 5 question, self-administered visual analog scale (VAS) where patients use 0 (worst health) to 100 (best health) to indicate how they view their health.
• Adverse Events [ Time Frame: Up to approximately 48 months ]
  Safety and tolerability will be evaluated by review of type, incidence, severity (as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0), seriousness, and relationship to study medications of adverse events (AEs) and any laboratory abnormalities

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Gedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or Metastatic HR+/HER2- Breast Cancer (VIKTORIA-1)
• Official Title: Phase 3, Open-Label, Randomized, Study Comparing Gedatolisib Combined With Fulvestrant & With or Without Palbociclib to Standard-of-Care Therapies in Patients With HR-Positive, HER2-Negative Advanced Breast Cancer Previously Treated With a CDK4/6 Inhibitor in Combination w/Non-Steroidal Aromatase Inhibitor Therapy
• Brief Summary: This is a Phase 3, open-label, randomized, clinical trial evaluating the efficacy and safety of gedatolisib plus fulvestrant with or without palbociclib for the treatment of patients with locally advanced or metastatic HR+/HER2- breast cancer following progression on or after CDK4/6 and aromatase inhibitor therapy.
• Detailed Description: This is a Phase 3, open-label, randomized clinical trial evaluating the efficacy and safety of gedatolisib plus fulvestrant with or without palbociclib 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 progression on or after CDK4/6 and aromatase inhibitor therapy. Gedatolisib is an intravenously administered pan-PI3K/mTOR inhibitor. Palbociclib is a CDK4/6 inhibitor. Fulvestrant is a selective estrogen receptor degrader (SERD). Subjects will be assessed for PIK3CA status and then randomized to treatment arms according to their confirmed PIK3CA mutation status.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Drug: Gedatolisib
  Gedatolisib 180 mg IV given weekly for 3 weeks (Days 1, 8, 15) followed by 1 week off
  Other Names:

  • PF-05212384
  • PKI-587
• Drug: Palbociclib
  Palbociclib 125 mg PO given daily for 3 weeks (21 days), followed by 1 week off
  Other Names:

  • IBRANCE
  • PD-0332991
• Drug: Fulvestrant
  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
  Other Name: Faslodex
• Drug: Alpelisib
  Alpelisib 300 mg PO (2 × 150 mg tablets) given daily for 4 weeks (28 days)
  Other Names:

  • Piqray
  • Vijoice
  • BYL719

Study Arms

• Experimental: Arm A - Patients Lacking PIK3CA Mutations (WT)
  Gedatolisib + Palbociclib + Fulvestrant
  Interventions:

  • Drug: Gedatolisib
  • Drug: Palbociclib
  • Drug: Fulvestrant
• Experimental: Arm B - Patients Lacking PIK3CA Mutations (WT)
  Gedatolisib + Fulvestrant
  Interventions:

  • Drug: Gedatolisib
  • Drug: Fulvestrant
• Active Comparator: Arm C - Patients Lacking PIK3CA Mutations (WT)
  Fulvestrant
  Intervention: Drug: Fulvestrant
• Experimental: Arm D - Patients with PIK3CA Mutation (MT)
  Gedatolisib + Palbociclib + Fulvestrant
  Interventions:

  • Drug: Gedatolisib
  • Drug: Palbociclib
  • Drug: Fulvestrant
• Active Comparator: Arm E - Patients with PIK3CA Mutation (MT)
  Alpelisib + Fulvestrant
  Interventions:

  • Drug: Fulvestrant
  • Drug: Alpelisib
• Experimental: Arm F - Patients with PIK3CA Mutation (MT)
  Gedatolisib + Fulvestrant
  Interventions:

  • Drug: Gedatolisib
  • Drug: Fulvestrant

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 12, 2022): 701
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2026
• Estimated Primary Completion Date: September 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of metastatic or locally advanced breast cancer 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 on it for the duration of the study.
2. Negative pregnancy test for women of childbearing potential. Female subjects of childbearing potential must use an effective and/or acceptable contraceptive method from screening until 1 year after the last dose of study treatment
3. Confirmed diagnosis of estrogen receptor positive and/or progesterone receptor positive, as per American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines (2020), based on most recent tumor biopsy utilizing an assay consistent with local standards
4. Documented HER2 immunohistochemistry (IHC) negative as per ASCO-CAP 2018 guidance
5. Adequate archival or fresh tumor tissue for the analysis of PIK3CA mutational status
6. Subject must have documentation of radiological disease progression on or after the last prior treatment and also have radiologically evaluable disease (measurable and/or non-measurable) according to RECIST v1.1, per local assessment. Subjects with bone only disease must have lytic or mixed lytic/blastic lesions that can be accurately assessed; bone only blastic lesions with no soft tissue component is not allowed.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
8. Life expectancy of at least 3 months
9. Progressed during or after CDK4/6 inhibitor combination treatment with non-steroidal aromatase inhibitor (AI)
10. Adequate bone marrow, hepatic, renal and coagulation function

Exclusion Criteria:

1. History of malignancies other than adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥3 years
2. Prior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor, a protein kinase B (Akt) inhibitor, or a mechanistic target of rapamycin (mTOR) inhibitor
3. Prior treatment with chemotherapy and antibody drug conjugates for advanced disease is not permitted (prior adjuvant or neoadjuvant chemotherapy is permitted)
4. More than 2 lines of prior endocrine therapy treatment
5. Bone only disease that is only blastic with no soft tissue component
6. Subjects with type 1 diabetes or uncontrolled type 2 diabetes

7. Known and untreated, or active, brain or leptomeningeal metastases

   a. Subjects with previously treated central nervous system (CNS) metastases may be enrolled in the study if they meet the following criteria: do not require supportive therapy with steroids; do not have seizures and do not exhibit uncontrolled neurological symptoms; stable disease confirmed by radiographic assessment within at least 4 weeks prior to enrollment

8. Patients with advanced, symptomatic, visceral spread that are at risk of life-threatening complication in the short-term

9. History of clinically significant cardiovascular abnormalities such as: Congestive heart failure (New York Heart Association (NYHA) classification ≥ II within 6 months of study entry

   1. Myocardial infarction within 12 months of study entry
   2. History of any uncontrolled (or untreated) clinically significant cardiac arrhythmias, (e.g., ventricular tachycardia), complete left bundle branch block, high grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block), supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months
   3. Uncontrolled hypertension defined by systolic blood pressure (SBP) ≥160 mmHg and/or diastolic blood pressure (DBP) ≥100 mmHg, with or without antihypertensive medication (initiation or adjustment of antihypertensive medication[s] is allowed prior to screening)

   4. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:

      • i. Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, or history of clinically significant/symptomatic bradycardia
      • ii. On screening, inability to determine the corrected QT interval using Fridericia's formula (QTcF) on the ECG (i.e., unreadable or not interpretable) or QTcF >480 msec (determined by mean of triplicate ECGs at screening)
10. Known hypersensitivity to the study drugs or their components
11. Pregnant or breast-feeding women

12. Concurrent participation in another interventional clinical trial

    1. Subjects must agree not to participate in another clinical trial (other than observational) at any time during participation in VIKTORIA-1.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Nadene Zack, MS; 844-310-3900; VIKTORIA-1_TRIAL@CELCUITY.COM

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czechia, France, Germany, Greece, Hungary, India, Italy, Korea, Republic of, Mexico, Poland, Romania, Singapore, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT05501886
• Other Study ID Numbers: CELC-G-301; 2021-005235-24 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Celcuity Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: Celcuity Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Nadene Zack; Celcuity Inc

• PRS Account: Celcuity Inc
• Verification Date: July 2023