A Study to Learn About a New Medicine Called ARV-471 (PF-07850327) in People Who Have Advanced Metastatic Breast Cancer.

JRCT ID: jRCT2031220651

Registered date:22/02/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: ER+/HER2 Advanced Breast Cancer
• Date of first enrollment: 14/03/2023
• Target sample size: 560
• Countries of recruitment: Puerto Rico,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Drug: ARV-471
orally, once daily on a 28-day continuous dosing schedule
Other Name: PF-07850327
Drug: Fulvestrant
intramuscularly on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle starting from C2D1 (28-day cycle)

Outcome(s)

Primary Outcome

Primary Outcome Measures :
1.Progression Free Survival (PFS) [ Time Frame: From randomization date (every 8 weeks for the first 48 weeks and then every 12 weeks thereafter) to date of first documentation of progression OR death (approximately 2 years). ]
Progression-free survival is defined as the time interval from the date of randomization to the date of first documented tumor progression determined by blinded independent central review (BICR) assessment as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or death due to any cause, whichever come first.

Secondary Outcome

Secondary Outcome Measures :
1.Overall survival (OS) [ Time Frame: From randomization date (every 3 months) to date of death (approximately 3 years) ]
Overall survival is defined as the time interval from the date of randomization to the date of documented death due to any cause.

2.Objective Response Rate (ORR) [ Time Frame: From randomization date (every 8 weeks during the first 48 weeks and then every 12 weeks) to the date of progression OR death (approximately to 2 years). ]
Objective response rate is defined as the proportion of participants who have a confirmed CR or PR, as best overall response assessed by BICR as per RECIST 1.1, from the date of randomization to the date of disease progression, death due to any cause, whichever occurs first.

3.Duration of response (DR) [ Time Frame: From the date of the first objective response (every 8 weeks during the first 48 weeks and then every 12 week) to the date of disease progression or death (approximately to 2 years). ]
Duration of response is defined as the time from first documented evidence of CR or PR until progressive disease (PD) as determined by BICR assessment as per RECIST 1.1 or death due to any cause, whichever occurs first.

4.Clinical Benefit Rate [ Time Frame: From randomization date (every 8 weeks during the first 48 weeks and then every 12 weeks) to the date of progression or death (approximately to 2 years). ]
Clinical benefit rate is defined as the proportion of participants who have a confirmed CR, PR at any time, or SD or nonCR/non PD for at least 24 weeks determined by BICR assessment as per RECIST 1.1, from the date of randomization until disease progression, death due to any cause, whichever occurs first.

5.Number of participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs), electrocardiogram (ECG) and laboratory abnormalities [ Time Frame: From screening until 28 days after the last dose (approximately 2 years). ]
Incidence of participants with TEAEs, SAEs ECGs and laboratory abnormalities. TEAE/SAE and laboratory abnormalities will be graded according to NCI CTCAE V5.

6.QT Interval (QTc) [ Time Frame: From baseline to end of treatment (approximately 2 years). ]
Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) are performed.

7.Plasma Concentration Versus Time of ARV-471 [ Time Frame: From randomization date up to cycle 7 (each cycle is 28 days). ]
Plasma concentrations of ARV-471

8.Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L) [ Time Frame: From screening and every cycle until cycle 6 (each cycle is 28 days), and then every other cycle until 28 days after the last dose (approximately 2 years). ]
Change from baseline and time to deterioration between treatment comparison in Quality of Life using the EQ-5D 5L questionnaire.

9.Disease-related Quality of Life will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30) [ Time Frame: From screening and every cycle until cycle 6 (each cycle is 28 days), and then every other cycle until 28 days after the last dose (approximately 2 years). ]
Change from baseline and time to deterioration between treatment comparison in Quality of Life using the EORTC QLQ-C30 questionnaire.

10.Disease- and treatment-related Quality of Life will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) breast cancer module (QLQ-BR23) questionnaire [ Time Frame: From screening and every cycle until cycle 6 (each cycle is 28 days), and then every other cycle until 28 days after the last dose (approximately 2 years). ]
Change from baseline and time to deterioration between treatment comparison in Quality of Life Using the EORTC QLQ-BR23 (Breast) questionnaire.

11.Clinical Pain and its impact on functioning will be assessed using Brief Pain Inventory Short Form (BPI-SF) questionnaire. [ Time Frame: From screening and every cycle until cycle 6 (cycle=28 days) and then every other cycle until 28 days after the last dose (appr. 2 yrs).The modified BPI-SF (worst pain severity and pain interference) daily from baseline until the EOT (appr 2 yrs) ]
Change from baseline and time to deterioration between treatment comparison in Brief Pain Inventory Short Form questionnaire.

12.circulating deoxyribonucleic acid (DNA) [ Time Frame: From baseline to end of treatment (approximately 2 years). ]
Quantitative changes from baseline

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Inclusion Criteria:
*Adult participants with loco-regional recurrent or metastatic breast disease not amenable to surgical resection or radiation therapy
*Confirmed diagnosis of ER+/HER2- breast cancer
*Prior therapies for locoregional recurrent or metastatic disease must fulfill all the following criteria:
*One line of CDK4/6 inhibitor therapy in combination with endocrine therapy
*<=1 endocrine therapy in addition to CDK4/6 inhibitor with ET
*Most recent endocrine treatment duration must have been given for >=6 months prior to disease progression
*Radiological progression during or after the last line of therapy
*Measurable disease evaluable per Response Evaluation Criterion in Solid Tumors (RECIST) v.1.1 or non-measurable bone-only disease
*Eastern Cooperative Oncology Group (ECOG) performance status 0-1
*Participants should be willing to provide blood and tumor tissue

Exclude criteria

Exclusion Criteria:
*Participants with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term
*Prior treatment with:
*ARV-471, fulvestrant, mTOR, PI3K, AKT pathway inhibitors, PARP inhibitor for any setting
*other investigational novel endocrine therapy (ie, SERD, SERCA, CERAN) for any setting
*prior CDK4/6 inhibitor treatment in the neoadjuvant/ adjuvant setting
*prior chemotherapy for advanced/metastatic disease
*Inadequate liver, kidney and bone marrow function
*Active brain metastases
*Participants with significant concomitant illness

Related Information

• Primary Sponsor: Kawai Norisuke
• Secondary ID(s): NCT05654623