Recruiting NCT06982521

Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer

Phase III Interventional PIK3CA Mutation HER2- Negative Breast Cancer Hormone Receptor Positive Tumor Breast Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Zovegalisib, Capivasertib, Fulvestrant.
Who it may be relevant to: Registry conditions: PIK3CA Mutation, HER2- Negative Breast Cancer, Hormone Receptor Positive Tumor, Breast Cancer. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Austria, Belgium +19
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

A Phase 3 Open-Label Randomized Study Assessing the Efficacy and Safety of RLY-2608 + Fulvestrant Versus Capivasertib + Fulvestrant as Treatment for PIK3CA-mutant Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Locally Advanced or Metastatic Breast Cancer Following Recurrence or Progression On or After Treatment With a CDK4/6 Inhibitor

Overview

This is a global, multicenter, open-label, randomized Phase 3 study comparing the efficacy and safety of RLY-2608 (zovegalisib) + fulvestrant to capivasertib + fulvestrant for the treatment of patients with HR+/HER2- ABC with PIK3CA mutation following recurrence or progression on or after treatment with a CDK4/6 inhibitor.

Interventions

Drug Zovegalisib
400 mg orally BID administered daily on a 28-day treatment cycle
Drug Capivasertib
400mg orally BID administered on an intermittent weekly dosing schedule. Patients will dose on Days 1 through 4 each week of a 28-day treatment cycle
Drug Fulvestrant
500 mg intramuscularly administered on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (28-day treatment cycle)

Primary outcome measures

Progression-Free Survival (PFS) within the overall and kinase population by blinded independent central review (BICR) [Time frame: The time from date of randomization until radiographic progression per RECIST v1.1, or death due to any cause, up to approximately 77 months]

Secondary outcome measures (10)

Overall Survival (OS) within the overall and kinase populations [Time frame: The time from randomization to the date of death by any cause, up to approximately 77 months]
PFS by Investigator within the overall and kinase populations [Time frame: The time from date of randomization until radiographic progression per RECIST v1.1, or death due to any cause, up to approximately 77 months]
Objective Response Rate (ORR) within the overall and kinase populations [Time frame: Up to approximately 77 months]
Duration of Response (DOR) within the overall and kinase populations [Time frame: Up to approximately 77 months]
Clinical Benefit Rate (CBR) within the overall and kinase populations [Time frame: Up to approximately 77 months]
Occurrence/frequency of Adverse Events (AEs) and its relationship to the study drugs (safety and tolerability) within the overall and kinase populations [Time frame: Up to approximately 77 months]
Plasma concentrations of zovegalisib (and its metabolites as appropriate) [Time frame: Approximately every 2 weeks in Cycle 1 (4-week cycle) and during Cycles 2 and 3]
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) scale/item scores including change from baseline and time to deterioration within overall and kinase populations [Time frame: Up to approximately 77 months]
EORTC Quality of Life Questionnaire Breast Cancer-Specific Module (EORTC QLQ-BR23) scale/item scores including change from baseline and time to deterioration within the overall and kinase populations [Time frame: Up to approximately 77 months]
Health state utility data for economic evaluation by EQ-5D-5L health state utility index within the overall and kinase populations [Time frame: Up to approximately 77 months]

Eligibility criteria

Inclusion criteria

Patient has ECOG performance status of 0-1
One or more known primary oncogenic PIK3CA mutation(s)
Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with a gonadotropin-releasing hormone (GnRH) agonist. Patients are to have commenced treatment with a GnRH agonist at least 2 weeks prior to randomization and must be willing to continue on it for the duration of the study.
Histologically or cytologically confirmed diagnosis of HR+/HER2- locally advanced or metastatic breast cancer (ABC) with radiological or objective evidence of recurrence or progression; locally advanced disease must not be amenable to resection with curative intent
Measurable disease per RECIST v1.1 or evaluable bone-only disease.
Must have radiological evidence of progression on or after previous treatment for HR+/HER2- ABC with:

At least 1 and no more than 2 lines of endocrine therapy (ET) in the (neo)adjuvant setting with recurrence on or within 12 months of completion or in the ABC setting
Only 1 prior line of CDK4/6 inhibitor therapy in one of the following settings:

CDK4/6 inhibitor + ET in the ABC setting
CDK4/6 inhibitor therapy in the adjuvant setting if progression occurred during or within 12 months of completion of adjuvant CDK4/6 inhibitor with ET
Patients who progressed during or within 12 months of completion of adjuvant CDK4/6 inhibitor and after receiving CDK4/6 inhibitor therapy in the advanced setting are considered to have had >1 prior line of CDK4/6 inhibitor and are not eligible

Exclusion criteria

Prior treatment with any of the following:

CDK2 inhibitors. Prior treatment with other investigational CDK inhibitors could be permitted upon discussion and approval from the Sponsor
PIK3, AKT, or mTOR inhibitors or any agent whose mechanism of action is the inhibit the PIK3/AKT/mTOR pathway
Immunotherapy
Antibody drug conjugates
Type 1 diabetes, or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥ 140 mg/dL (7.8 mmol/L), or glycosylated hemoglobin (HbA1c) ≥7.0% (≥ 53 mmol/mol).
Clinically significant, uncontrolled cardiovascular disease
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
Known active uncontrolled or symptomatic CNS metastases associated with progressive neurological symptoms or requiring ongoing corticosteroids or anticonvulsants for symptomatic control
Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
History of hypersensitivity to fulvestrant or drugs in a similar class as fulvestrant, zovegalisib, or capivasertib, including their excipients
Known activating AKT mutations, loss-of-function PTEN mutations, or loss of PTEN expression resulting in oncogenic pathway activation downstream of PI3K

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Open label
Primary purpose: Treatment