PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors

NCT03284723 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: C05410012017-002538-22
• Study Type: interventional
• Target: 95
• Locations: 6 countries
• Sites: 46

Brief Summary

The study will evaluate the safety, pharmacokinetics and pharmacodynamics of increasing doses of PF-06804103 in patients with HER2 positive and negative breast and gastric cancer (HER2 positive only and gastric were studied in Part 1A only). The study will expand to look at selected doses in patients with HER2 positive and negative breast cancer.

Conditions

Breast Neoplasms

Keywords

HER2; PF-06804103; ADC; breast cancer; neoplasms; solid tumors; human epidermal growth receptor 2

Outcome Measures

Primary Outcomes (11)

• Number of Participants With Cycle 1 (21 Days) Dose-Limiting Toxicities (DLTs) in Part 1A

  A DLT was any of the following adverse events(AEs) in the first cycle of treatment (within 21 days of first dose). (1) Hematologic: Grade 4 neutropenia lasting \>7 days; febrile neutropenia; Grade \>＝3 neutropenic infection; Grade \>＝3 thrombocytopenia with bleeding; thrombocytopenia; (2) Non-hematologic: Grade \>=3 toxicities that were considered clinically significant; delayed by more than 2 weeks in receiving the next scheduled cycle due to persisting treatment related toxicities; concurrent AST or ALT \>3x ULN and total bilirubin \>2x ULN; any Grade 5 event.

  First cycle, Day 1 up to Day 21

• Number of Participants Wth Cycle 1 (28 Days) Dose-Limiting Toxicities (DLTs) in Part 1B

  A DLT was any of the following adverse events(AEs) in the first cycle of treatment (within 28 days of first dose). (1) Hematologic: including a delay greater than 1 week in administration of the next scheduled dose of study treatment due to persistent treatment-related toxicities; Grade 4 neutropenia lasting \>7 days; febrile neutropenia; Grade \>=3 neutropenic infection; Grade \>=3 thrombocytopenia with bleeding; thrombocytopenia. (2) Non-hematologic: including Grade \>=3 toxicities that are considered clinically significant; Grade 3 QTc prolongation despite correction of reversible causes; delayed by \>2 week in receiving the next scheduled dose of any study treatment due to persisting treatment-related toxicities; inability to administer at least 80% of the planned palbociclib or letrozole or 100% of the planned PF-06804103 doses during Cycle 1 due to toxicity related to the study treatment; concurrent AST or ALT \>3x ULN and total bilirubin \>2x ULN; any Grade 5 event.

  First Cycle, Day 1 up to Day 28

• Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs (TEAEs) were defined as those with initial onset or increasing in severity after the first dose of study medication. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator.

  From the first dose of study treatment up to a minimum of 28 calendar days after the last dose of study treatment (maximum duration between first and last dose: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)

• Number of Participants With Laboratory Abnormalities-Hematology

  Participants who experienced hematology laboratory test abnormalities were summarized according to worst toxicity grade observed for each hematology laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated). This outcome measure calculated the number of participants with hematology laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above, including the following parameters: anemia, INR increased, lymphocyte count decreased, neutrophil count decreased, white blood cell decreased.

  From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)

• Number of Participants With Laboratory Abnormalities-Chemistries

  Participants who experienced chemistry laboratory test abnormalities were summarized according to worst toxicity grade observed for each chemistry laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated). This outcome measure calculated the number of participants with chemistry laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above, including the following parameters: alanine aminotransferase (ALT) increased, alkaline phosphatase (ALP) increased, aspartate aminotransferase (AST) increased, hyperglycemia, hypermagnesemia, hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia, lipase increased, serum amylase increased.

  From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)

• Number of Participants With Laboratory Abnormalities-Urinalysis

  Participants who experienced urinalysis laboratory test abnormalities were summarized according to worst toxicity grade observed for each urinalysis laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated). This outcome measure calculated the number of participants with urinalysis laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above.

  From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)

• Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria

  Blood pressure (BP), including systolic BP (SBP) and diastolic BP (DBP), and pulse rate were recorded in a supine or seated position.

  From baseline up to follow up (at least 28 days and no more than 35 days after discontinuation of treatment), maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B

• Percentage of Participants With Objective Response in Part 2

  Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 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 axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.

  Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks)

• Duration of Response (DR) in Part 2

  Duration of response (DR) was the time from first documentation of PR or CR to date of first documentation of progressive disease (PD) or death due to any cause. 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 axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.

  Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks)

• Progression-Free Survival (PFS) in Part 2

  Progression-free survival (PFS) was the time from randomization date to date of first documentation of PD or death due to any cause. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.

  Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks)

• Time to Tumor Progression (TTP) in Part 2

  Time to progression (TTP) was the time from start date to the date of the first documentation of PD. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.

  Baseline, every 6 weeks from the start of treatment until disease progression, death, or withdrawal from treatment (maximum treatment duration: 49.4 weeks)

Secondary Outcomes (26)

• Percentage of Participants With Objective Response in Part 1

  Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)

• Duration of Response (DR) in Part 1

  Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)

• Progression-Free Survival (PFS) in Part 1

  Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)

• Time to Tumor Progression (TTP) in Part 1

  Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)

• Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103

  Prior to the start of treatment on Day 1 of Cycle 1 up to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)

Study Arms (2)

PF-06804103

EXPERIMENTAL

Study Treatment

Drug: PF-06804103

PF-06804103+Combination Regimen

EXPERIMENTAL

Study Treatment

Drug: PF-06804103 + Palbociclib +Letrozole

Interventions

PF-06804103 DRUG

Dose Escalation Part - 1A Dose Expansion Part - 2A

PF-06804103

PF-06804103 + Palbociclib +Letrozole DRUG

Dose Escalation - Part 1B Dose Expansion - Part 2B

PF-06804103+Combination Regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HER2 positive breast cancer or gastric cancer that is resistant to standard therapy or for which no standard therapy is available (Part 1A only)
• HER2 positive and negative breast cancer (Part 2A)
• HER2 negative breast cancer (Part 1B \& Part 2B)
• Performance status of 0 or 1
• Adequate bone marrow, kidney and liver function

You may not qualify if:

• Known CNS disease including, but not limited to, metastases
• History of exposure to certain cumulative doses of anthracyclines
• Grade 3 or higher hypersensitivity reaction to prior receipt of any antibody therapy
• Active and clinically significant bacterial, fungal, or viral infection
• Abnormal cardiac function defined by a LVEF \<50% by ECHO or MUGA
• Patients with previous history or active interstitial lung disease or pulmonary fibrosis, or a history of other clinically significant lung diseases

Sponsors & Collaborators

• Pfizer: lead

Study Sites (46)

Banner-University Medical Center Tucson

Tucson, Arizona, 85719, United States

Location

The University of Arizona Cancer Center - North Campus

Tucson, Arizona, 85719, United States

Location

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

Location

UCLA Health (main campus)

Los Angeles, California, 90095, United States

Location

UCLA Hematology/Oncology

Los Angeles, California, 90095, United States

Location

Santa Monica - UCLA Medical Center and Orthopaedic Hospital

Santa Monica, California, 90404, United States

Location

UCLA Dept of Medicine - Hematology/Oncology, Santa Monica

Santa Monica, California, 90404, United States

Location

UCLA Health, Santa Monica

Santa Monica, California, 90404, United States

Location

Northside Hospital Inc.- GCS/Athens

Athens, Georgia, 30606, United States

Location

Atlanta Cancer Care - Atlanta

Atlanta, Georgia, 30342, United States

Location

Northside Hospital, Inc. - GCS/Northside

Atlanta, Georgia, 30342, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Northside Hospital,Inc.-GCS /Blairsville

Blairsville, Georgia, 30512, United States

Location

Northside Hospital, Inc. - GCS/Canton

Canton, Georgia, 30114, United States

Location

Atlanta Cancer Care - Cumming

Cumming, Georgia, 30041, United States

Location

Northside Hospital, Inc.-GCS/Stemmer

Decatur, Georgia, 30033, United States

Location

Suburban Hematology-Oncology Associates - Duluth

Duluth, Georgia, 30096, United States

Location

Atlanta Cancer Care - Lake Spivey

Jonesboro, Georgia, 30236, United States

Location

Suburban Hematology-Oncology Associates- Lawrenceville

Lawrenceville, Georgia, 30046, United States

Location

Northside Hospital, Inc. - GCS/Macon

Macon, Georgia, 31217, United States

Location

Northside Hospital, Inc. GCS/Kennestone

Marietta, Georgia, 30060, United States

Location

Oncology Hematology West, PC dba Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah, Huntsman Cancer Hospital

Salt Lake City, Utah, 84112, United States

Location

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Macquarie University

Macquarie Park, New South Wales, 2109, Australia

Location

Istituto Clinico Humanitas U. O. Oculistica

Milan, Lombardy, 20089, Italy

Location

Azienda Socio-Sanitaria Territoriale Monza

Monza, MB, 20900, Italy

Location

Fondazione IRCCS, Istituto Nazionale dei Tumori

Milan, MI, 20133, Italy

Location

Divisione di Cardiologia - Istituto Europeo di Oncologia Divisione di Medicina Nucleare

Milan, MI, 20141, Italy

Location

Istituto Europeo di Oncologia

Milan, MI, 20141, Italy

Location

LLC "Clinica UZI 4D"

Pyatigorsk, Stavropol Kray, 357502, Russia

Location

Private Healthcare Institution "Clinical hospital "RZD-Medicine" of Saint-Petersburg

Saint Petersburg, 195271, Russia

Location

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Universitario Quirón Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Related Publications (1)

• Meric-Bernstam F, Calvo E, Lee KS, Moreno V, Park YH, Rha SY, Chalasani P, Zhong W, Zhou L, Pirie-Shepherd S, Leung ACF, Curigliano G. Safety and Tolerability of a Novel Anti-HER2 Antibody-Drug Conjugate (PF-06804103) in Patients with HER2-Expressing Solid Tumors: A Phase 1 Dose-Escalation Study. Mol Cancer Ther. 2023 Oct 2;22(10):1191-1203. doi: 10.1158/1535-7163.MCT-23-0101.

  PMID: 37420274 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms

Interventions

PF-06804103

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

On 10 February 2021, a decision was made by the sponsor to terminate the study due to business reasons. The decision was not due to any urgent patient safety concerns, study conduct issues, or regulatory authority requests concerning treatment with the PF-06804103 compound. Part 2B had not enrolled prior to the termination of the study.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2017
• First Posted: September 15, 2017
• Study Start: November 1, 2017
• Primary Completion: August 31, 2021
• Study Completion: August 31, 2021
• Last Updated: September 3, 2024
• Results First Posted: September 3, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (5); US (26); AU (2); RU (2); KR (6); ES (5)