FPA150 in Patients With Advanced Solid Tumors

NCT03514121 | Terminated Early Phase 1 Results FDA Drug

• 1 other identifier: FPA150-001
• Study Type: interventional
• Target: 95
• Locations: 2 countries
• Sites: 18

Brief Summary

This is a multi-center study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of FPA150, an anti-B7H4 antibody alone or in combination with pembrolizumab an anti-PD1 antibody in patients with advanced solid tumors. The Phase 1a, open-label, cohort will identify a recommended dose of FPA150 to use for Phase 1a Combination (FPA150 and Pembrolizumab) Safety Lead-in and for Phase 1b monotherapy cohorts.

Conditions

Breast Cancer; Ovarian Cancer; Endometrial Cancer; Advanced Solid Tumors

Outcome Measures

Primary Outcomes (6)

• Phase 1a Monotherapy: Number of Participants Experiencing Grade 3 and Grade 4 Adverse Events (AEs)

  An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject that was administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. Grade 3 and 4 severity ratings were defined as follows: Grade 3: Severe or medically significant but non-immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; severe AE Grade 4: Life-threatening consequences; urgent intervention indicated

  From day 1 up to 28 days after last dose (median [min, max] treatment duration= 9.143 [3.00, 52.00] weeks)

• Phase 1a Monotherapy: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

  DLTs were defined as any of the following events regardless of attribution (except for those events clearly due to the underlying disease or extraneous causes): Any Grade 3 or higher non-hematologic toxicity (except Grade 3 nausea, vomiting, and diarrhea) that occurred within the first 21 days of treatment. Grade 3 nausea, vomiting, diarrhea lasting \>72 hours, that occurred within the first 21 days of treatment. Febrile neutropenia and/or documented infection, Grade 4 neutropenia that lasted more than 7 days, Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia accompanied by bleeding within first 21 days of treatment. Aspartate aminotransferase (AST) / alanine transaminase (ALT) \>3 × upper limit of normal (ULN) and concurrent total bilirubin \> 2 × ULN that was not related to liver involvement with cancer. Other Grade 3 laboratory values that did not resolve within 72 hours. Any Grade 4 laboratory value regardless of clinical sequelae

  Up to 21 days

• Phase 1a Monotherapy: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

  TEAEs were defined as an AE that began or worsened in severity after at least one dose of study treatment (FPA150) had been administered. Clinically significant laboratory abnormalities and ECG abnormalities are included as TEAEs.

  From day 1 up to 28 days after last dose (median [min, max] treatment duration= 9.143 [3.00, 52.00] weeks)

• Phase 1b Monotherapy: Number of Participants Experiencing AEs

  An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject that was administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A serious AE is defined as any AE that resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality/birth defect or important medical events. Clinically significant laboratory abnormalities and ECG abnormalities were included as TEAEs.

  From day 1 up to 28 days after last dose (median [min, max] treatment duration= 6.35 [3.00, 108.14] weeks)

• Phase 1a Combination Safety Lead-In & Phase 1b Combination: Number of Participants Experiencing AEs

  An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject that was administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A serious AE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgment may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above.

  From day 1 up to 28 days after last dose (median [min, max] treatment duration= 12.00 [6.00, 36.43] weeks)

• Phase 1a Combination Safety Lead-In & Phase 1b Combination: Number of Participants Experiencing Grade 3 and Grade 4 AEs

  An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject that was administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A serious AE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgment may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above.

  From day 1 up to 28 days after last dose (median [min, max] treatment duration= 12.00 [6.00, 36.43] weeks)

Secondary Outcomes (19)

• Phase 1a Monotherapy: Number of Participants With ADAs to FPA150

  From day 1 up to 28 days after last dose (median [min, max] treatment duration= 9.143 [3.00, 52.00] weeks)

• Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 at Baseline

  Cycle 1 day 1 pre-dose (baseline)

• Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 Postbaseline

  From day 1 up to 28 days after last dose (median [min, max] treatment duration= 6.35 [3.00, 108.14] weeks)

• Phase 1b Monotherapy: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  Up to approximately 24 months

• Phase 1b Monotherapy: Duration of Response (DOR) Per RECIST v1.1

  Up to approximately 24 months

Study Arms (1)

Phase 1a dose escalation/1b dose expansion

EXPERIMENTAL

The study consists of Phase 1a dose escalation, Phase 1a dose exploration, Phase 1a combination safety-lead-in and Phase 1b dose expansion

Biological: FPA150; Biological: Pembrolizumab

Interventions

FPA150 BIOLOGICAL

A monoclonal antibody against B7-H4

Phase 1a dose escalation/1b dose expansion

Pembrolizumab BIOLOGICAL

An anti-PD1 antibody

Phase 1a dose escalation/1b dose expansion

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed solid tumors except primary central nervous system (CNS) tumors.
• Disease that is unresectable, locally advanced, or metastatic.
• Patients must have had progressive disease during or after, or refused, appropriate standard therapy for their tumor type.
• All patients must have at least one measurable lesion at baseline according to RECIST v1.1; tumor sites situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are not considered measurable unless there has been demonstrated progression in the lesion.
• Adequate washout for prior anti-cancer therapy (ie, ≥ 5 half-lives or 4 weeks since the last dose, whichever is shorter).
• Availability of archival tumor tissue and consent to providing archival tumor for retrospective biomarker analysis, or willingness to undergo a fresh tumor biopsy during screening (a biopsy is required for patients in the Phase 1a Dose Exploration portion).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Prior radiotherapy must be completed at least 2 weeks before the first dose of study drug.
• Prior radiopharmaceuticals (eg strontium, samarium) must be completed at least 8 weeks before the first dose of study drug.
• Prior surgery requiring general anesthesia must be completed one week before first study drug administration. Surgery requiring local/epidural must be completed at least 72 hours before first study drug administration.
• Screening laboratory values must meet the following criteria:
• Neutrophils ≥ 1200 cells/ µL
• Platelets ≥ 75 × 103/ µL
• Hemoglobin (Hb) ≥ 9.0 g/dL
• Serum creatinine \< 1.5× ULN or creatinine clearance (CrCl) of ≥ 40 mL/ minute

You may not qualify if:

• Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses \> 10 mg/day prednisone or equivalent daily) must be discontinued at least 2 weeks before the first dose of study drug. Short courses of high dose steroids or continuous low dose (prednisone \< 10 mg/day ) are allowed.
• Decreased cardiac function with New York Heart Association (NYHA) \> Class 2 at screening.
• Uncontrolled or significant heart disorder such as unstable angina.
• QT interval corrected for heart rate (QTc) per institutional guidelines \> 450 msec for males or \> 470 msec for females at screening.
• Current unresolved infection or history of chronic, active, clinically significant infection (viral, bacterial, fungal, or other) which, in the opinion of the Investigator, would preclude the patient from exposure to a biologic agent or may pose a risk to patient safety.
• Any uncontrolled medical condition or psychiatric disorder which, in the opinion of the Investigator, would pose a risk to patient safety or interfere with study participation or interpretation of individual patient results.
• Active, known, or suspected autoimmune disease. Patients with Type I diabetes mellitus, hypothyroidism requiring only hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger, are permitted to enroll.
• Known history of testing positive for human immunodeficiency virus (HIV) 1 or 2 or known acquired immunodeficiency syndrome (AIDS).
• Positive test for hepatitis B virus surface antigen (HBsAg) or detectable hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection.
• Ongoing adverse effects from prior treatment \> Grade 1 (with the exception of Grade 2 alopecia or peripheral neuropathy) based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
• Symptomatic interstitial lung disease or inflammatory pneumonitis.
• Untreated or active CNS or leptomeningeal metastases. Patients are eligible if metastases have been treated and patients are neurologically returned to baseline or neurologically stable (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks before the first dose of study drug.
• Evidence of coagulopathy or bleeding diathesis. Patients receiving stable therapeutic doses of anti-coagulants will be permitted.
• Transfusion of blood or platelets completed within 72 hours before the first dose of study drug.
• Any uncontrolled inflammatory GI disease including Crohn's Disease and ulcerative colitis

Sponsors & Collaborators

• Five Prime Therapeutics, Inc.: lead

Study Sites (18)

Honor Health

Scottsdale, Arizona, 85258, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Orchard Healthcare Research Inc.

Skokie, Illinois, 60077, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

Location

Medical Oncology Associates, PS

Spokane, Washington, 99208, United States

Location

National Cancer Center

Gyeonggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, 13620, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

ASAN Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

MeSH Terms

Conditions

Breast Neoplasms; Ovarian Neoplasms; Endometrial Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single arm trial with multiple cohorts

Study Record Dates

• First Submitted: March 27, 2018
• First Posted: May 2, 2018
• Study Start: March 27, 2018
• Primary Completion: April 21, 2021
• Study Completion: April 21, 2021
• Last Updated: November 22, 2024
• Results First Posted: November 22, 2024

Record last verified: 2022-01

Locations

US (13); KR (5)