Trial Outcomes & Findings for A Study to Learn About the Vepdegestrant (ARV-471, PF-07850327) in People With ER+/HER2- Locally Advanced or Metastatic Breast Cancer (BC) (NCT NCT05463952)

NCT ID: NCT05463952

Last Updated: 2024-11-13

Results Overview

DLT was defined as any adverse event (AE) or abnormal laboratory value which were related to ARV-471 and assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies occurring during the first 28 days of treatment that met at least 1 of the study specified criteria.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE1
• Target enrollment: 6 participants
• Primary outcome timeframe: Cycle 1 (28 days)
• Results posted on: 2024-11-13

Participant Flow

Japanese participants with estrogen receptor (ER+) or human epidermal growth factor receptor 2 (HER-2) locally advanced or metastatic breast cancer (mBC) were treated with ARV-471 (PF-07850327) as monotherapy. A total of 6 participants were enrolled.

Results are reported at primary completion date. Remaining results would be reported on completion of analysis at study completion date later.

Participant milestones

Measure	ARV-471 200 mg Participants received ARV-471 200 milligrams (mg) orally once daily (QD) with food, in continuous dosing over 28-day cycle (1 cycle = 28 days). Participants continued treatment at the discretion of the investigator until a treatment discontinuation criterion was met (disease progression; global deterioration of health status requiring discontinuation; unacceptable toxicity; pregnancy; significant protocol violation; lost to follow-up; participant refused further treatment; study terminated by sponsor; death).
Treatment STARTED	6
Treatment COMPLETED	0
Treatment NOT COMPLETED	6
Follow-up STARTED	4
Follow-up COMPLETED	4
Follow-up NOT COMPLETED	0

Reasons for withdrawal

Measure	ARV-471 200 mg Participants received ARV-471 200 milligrams (mg) orally once daily (QD) with food, in continuous dosing over 28-day cycle (1 cycle = 28 days). Participants continued treatment at the discretion of the investigator until a treatment discontinuation criterion was met (disease progression; global deterioration of health status requiring discontinuation; unacceptable toxicity; pregnancy; significant protocol violation; lost to follow-up; participant refused further treatment; study terminated by sponsor; death).
Treatment Progressive disease	4
Treatment Ongoing	2

Baseline Characteristics

A Study to Learn About the Vepdegestrant (ARV-471, PF-07850327) in People With ER+/HER2- Locally Advanced or Metastatic Breast Cancer (BC)

Baseline characteristics by cohort

Measure	ARV-471 200 mg n=6 Participants Participants received ARV-471 200 mg orally QD, in continuous dosing over 28-day cycle.
Age, Continuous	56.0 Years STANDARD_DEVIATION 6.10 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 1 (28 days)

Population: DLT evaluable analysis set included all enrolled participants who received at least 75% of the planned dose intensity of study treatment and either experienced DLT or did not have major protocol deviations during the DLT observation period.

DLT was defined as any adverse event (AE) or abnormal laboratory value which were related to ARV-471 and assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies occurring during the first 28 days of treatment that met at least 1 of the study specified criteria.

Outcome measures

Measure	ARV-471 200 mg n=6 Participants Participants received ARV-471 200 mg orally QD, in continuous dosing over 28-day cycle.
Number of Participants With Dose Limiting Toxicity (DLTs) During First Treatment Cycle	0 Participants

SECONDARY outcome

Timeframe: Day 1 of study treatment up to 35 days after last dose of study treatment (approximately 1.5 years)

An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness was judged by investigator. SAE was an AE resulted in any of the following outcomes: death, inpatient hospitalization or prolongation of existing hospitalization; was life-threatening experience (immediate risk of dying); resulted in persistent or significant disability/incapacity; congenital anomaly, a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: During study treatment, approximately 1.5 years

The following hematology parameters were assessed: hemoglobin, platelets, white blood cell (WBC), absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils and absolute basophils. Laboratory abnormality events were graded according to NCI CTCAE v 5.0 (grade 0=no change from normal or reference range, grade 1=mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: During study treatment, approximately 1.5 years

The following chemistry parameters were assessed: aspartate transaminase (AST), alkaline phosphatase (ALP), sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, phosphorus or phosphate, creatinine kinase (CK), amylase and lipase. Laboratory abnormality events were graded according to NCI CTCAE v 5.0 (grade 0=no change from normal or reference range, grade 1=mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through the end of the study treatment (approximately 1.5 years)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through the end of the study treatment (approximately 1.5 years)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through the end of the study treatment (approximately 1.5 years)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through the end of the study treatment (approximately 1.5 years)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through the end of the study treatment (approximately 1.5 years)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through the end of the study treatment (approximately 1.5 years)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through the end of the study treatment (approximately 1.5 years)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through the end of the study treatment (approximately 1.5 years)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through the end of the study treatment (approximately 1.5 years)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through the end of the study treatment (approximately 1.5 years)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through the end of the study treatment (approximately 1.5 years)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through the end of the study treatment (approximately 1.5 years)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through the end of the study treatment (approximately 1.5 years)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From start of study treatment until disease progression or death due to any cause (approximately 1.5 years)

ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) and partial response (PR) as per Response Evaluation Criteria in Solid Tumours (RECIST version [v] 1.1). BOR: best response was recorded from start of study treatment until disease progression or death due to any cause. CR: complete disappearance of all target lesions with exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<]10 millimeter [mm]). PR: greater than or equal to (>=) 30 percent (%) decrease under baseline of sum of diameters of all targets measurable lesions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. All target lesions were assessed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From start of study treatment until disease progression or death due to any cause (approximately 1.5 years)

CBR is defined as the percentage of participants with BOR of CR, PR and stable disease (SD) of 24 weeks duration or longer. As per RECIST v1.1. SD: Does not qualify for CR, PR or Progression. All target lesions must be assessed. Stable could follow PR only in the rare case that the sum increased by <20% from the nadir, but enough that a previously documented 30% decrease no longer held. CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease. All nodes, both target and non-target, must decrease to normal short axis <10 mm). No new lesions. PR: >= 30% decrease under baseline of sum of diameters of all targets measurable lesions. Short diameter was used in sum for target nodes, while longest diameter was used in sum for all other target lesions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From start of study treatment until disease progression or death due to any cause or censoring date (approximately 1.5 years)

PFS was defined as the time from first dose of study treatment (ie, start date) to the date of progression of disease (PD) or death due to any cause, whichever occurred first. PFS data was censored on the date of the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to an event, or for participants with an event after two or more missing tumor assessments. PD as per RECIST v1.1 for target lesions was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. For non-target lesions- PD was defined as unequivocal progression of pre-existing lesions. Analysis was performed using Kaplan-Meier method.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause (approximately 1.5 years)

Duration of response was defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first in participants with confirmed objective response (CR or PR). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. Analysis was performed using Kaplan-Meier method.

Outcome measures

Outcome data not reported

Adverse Events

ARV-471 200 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	ARV-471 200 mg n=6 participants at risk Participants received ARV-471 200 mg orally QD, in continuous dosing over 28-day cycle.
Blood and lymphatic system disorders Anaemia	16.7% 1/6 • Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)
Gastrointestinal disorders Abdominal discomfort	16.7% 1/6 • Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)
Gastrointestinal disorders Abdominal pain	16.7% 1/6 • Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)
Gastrointestinal disorders Constipation	16.7% 1/6 • Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)
Gastrointestinal disorders Nausea	16.7% 1/6 • Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)
General disorders Pyrexia	16.7% 1/6 • Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)
Immune system disorders Seasonal allergy	16.7% 1/6 • Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)
Infections and infestations COVID-19	16.7% 1/6 • Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)
Investigations Alanine aminotransferase increased	16.7% 1/6 • Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)
Investigations Aspartate aminotransferase increased	16.7% 1/6 • Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)
Metabolism and nutrition disorders Hypercalcaemia	16.7% 1/6 • Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	16.7% 1/6 • Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)
Nervous system disorders Dizziness	16.7% 1/6 • Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)
Skin and subcutaneous tissue disorders Pruritus	16.7% 1/6 • Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)
Skin and subcutaneous tissue disorders Rash	16.7% 1/6 • Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquires@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER