Breast CancerEarly Phase 1FPA150-001NCT03514121
FPA150 in Patients With Advanced Solid Tumors
A Early Phase 1 study testing FPA150 and Pembrolizumab in people with Breast Cancer and Ovarian Cancer, run by Five Prime Therapeutics, Inc. at 18 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Breast Cancer, Ovarian Cancer, Endometrial Cancer
- What is being tested?
- FPA150 and Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 18 sitesin 2 countries
- Study dates
- 27 Mar 2018to 21 Apr 2021
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All Inclusion Criteria for Phase 1a (Exception: Phase 1a Inclusion Criterion #1).
- Positive for B7-H4 expression in an archival or fresh tumor sample as evaluated by an accompanying validated central laboratory IHC assay. Archival tissue for patients enrolled in Cohort 1b1 (Breast Cancer) must be within 24 months prior to pre-screening.
- History of other malignancy is permitted provided it has been definitively treated with no evidence of recurrence within the past 2 years (Exception: Definitively treated non-melanoma skin cancer, lobular cancer in situ, and cervical cancer in situ within 2 years are permitted). Cohort Specific Phase 1b Criteria (monotherapy and combination therapy)
- Breast Cancer Cohorts:
- TNBC:
- Histologically or cytologically confirmed metastatic TNBC
Show all 21Show fewer
- At least two prior lines of systemic chemotherapy with at least one being administered in the metastatic setting
- HR+ Breast:
- Histologically or cytologically confirmed metastatic HR+ breast carcinoma
- Patients must have received at least two prior lines of hormonal therapy
- Patients must have received at least one prior line of systemic chemotherapy (in the adjuvant or metastatic setting)
- Ovarian Cancer (monotherapy):
- Histologically or cytologically confirmed diagnosis of recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma that is refractory to existing
- Progressive disease on or after at least two prior regimens of treatment including at least one platinum-containing regimen, or unable to tolerate additional chemotherapy
- Endometrial Cancer:
- Histologically or cytologically confirmed recurrent or persistent endometrial cancer that is refractory to curative or established treatments
- Progressive disease on or after at least one prior regimen of systemic chemotherapy, or unable to tolerate systemic chemotherapy
- Ovarian Cancer (combination):
- Histologically or cytologically confirmed diagnosis of recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma that is refractory to existing
- Progressive disease on or after at least two prior regimens of treatment including at least one platinum-containing regimen, or unable to tolerate additional chemotherapy
- No prior therapy with an anti-PD1 or PD-L1-directed agent
Who cannot join
- 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.
Show all 16Show fewer
- 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
- For Cohort 1b1 only: Patients with HER2 positive disease
Trial locations and contacts
18 sites in 2 countries.
18 sites in 2 countries
United States13 sites
Karmanos Cancer Institute
Detroit, Michigan, 48201
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Cedars-Sinai Medical Center
Los Angeles, California, 90048
UCLA
Los Angeles, California, 90095
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Yale Cancer Center
New Haven, Connecticut, 06520
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Utah Cancer Specialists
Salt Lake City, Utah, 84106
South Texas Accelerated Research Therapeutics
San Antonio, Texas, 78229
Sarcoma Oncology Research Center
Santa Monica, California, 90403
Honor Health
Scottsdale, Arizona, 85258
Orchard Healthcare Research Inc.
Skokie, Illinois, 60077
Medical Oncology Associates, PS
Spokane, Washington, 99208
South Korea5 sites
National Cancer Center
Gyeonggi-do, 10408
Seoul National University Bundang Hospital
Gyeonggi-do, 13620
Severance Hospital
Seoul, 03722
ASAN Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
About this study
Official title: A Phase 1a/1b Study of FPA150, an Anti-B7-H4 Antibody, in Patients With Advanced Solid Tumors
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.
Read the detailed description
This is a Phase 1a/1b open-label, multicenter study to evaluate the dosing, safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of FPA150 as monotherapy and in combination with pembrolizumab, an anti-PD1 antibody, in patients with advanced solid tumors.
This study includes a Phase 1a FPA150 Monotherapy Dose Escalation, Phase 1a Monotherapy Dose Exploration, Phase 1a combination Safety Lead-in (FPA150 + pembrolizumab), a Phase 1b FPA150 Monotherapy Dose Expansion, and a Phase 1b combination Dose Expansion (FPA150 + pembrolizumab).
The Phase 1a Monotherapy Dose Escalation will include an initial accelerated titration design followed by a standard 3+3 dose escalation design until the MTD and/or RD for Phase 1b is determined. The Phase 1a combination Safety Lead-In will start enrolling once the FPA150 monotherapy RD is identified in Phase 1a monotherapy dose escalation and will continue until the FPA150 MTD/RD in combination is identified. Phase 1a FPA150 monotherapy Dose Exploration may include cohorts that may enroll beyond 3 patients whose tumors express high levels of B7-H4 protein and/or have varying levels of B7H4 expression including low (<10% IHC 2+ or 3+ scores) or no expression on their tumor cells (up to 20 additional patients across all dose levels) to further evaluate safety, PK, pharmacodynamics, and clinical activity at that dose (to be conditional upon the dose level clearing DLT criteria).
Phase 1b will be the Dose Expansion (monotherapy and combination) portion of the study.
Enrollment into Phase 1b Dose Expansion will begin after identification of the MTD and/or RD in Phase 1a (monotherapy and Safety Lead-in). Preliminary efficacy will be evaluated in Phase 1b in planned expansion cohorts that include patients with specific tumor types that are B7-H4+ advanced solid tumors.
- Being tested
- FPA150, Pembrolizumab
- Medical subject headings
- Breast Neoplasms, Ovarian Neoplasms, Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FPA150Biological
A monoclonal antibody against B7-H4
PembrolizumabBiological
An anti-PD1 antibody
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: FPA150; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
All ADA samples were collected prior to dosing. A baseline ADA-positive patient was defined as a patient who had an ADA positive sample at baseline. Postbaseline treatment induced ADA positive is derived as participants with ADA negative at baseline and ADA positive at any postbaseline timepoint, or ADA positive at baseline and ADA positive with titer of at least 4-fold of the baseline titer at one or more postbaseline timepoint.
Measured: 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
All ADA samples were collected prior to dosing. A baseline ADA-positive patient was defined as a patient who had an ADA positive sample at baseline. Postbaseline treatment induced ADA positive is derived as participants with ADA negative at baseline and ADA positive at any postbaseline timepoint, or ADA positive at baseline and ADA positive with titer of at least 4-fold of the baseline titer at one or more postbaseline timepoint.
Measured: Cycle 1 day 1 pre-dose (baseline)
Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 Postbaseline
All ADA samples were collected prior to dosing. A baseline ADA-positive patient was defined as a patient who had an ADA positive sample at baseline. Postbaseline treatment induced ADA positive is derived as participants with ADA negative at baseline and ADA positive at any postbaseline timepoint, or ADA positive at baseline and ADA positive with titer of at least 4-fold of the baseline titer at one or more postbaseline timepoint.
Measured: 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)
ORR was defined as the percentage of participants who achieved best overall response (BOR) of either complete response (CR) or partial response (PR) based on investigator assessment of tumor lesions per RECIST v1.1. The BOR was the best response documented from first dose until the end of study, first disease progression, death, or start of new anti-cancer therapy, whichever was earlier.
Measured: Up to approximately 24 months
Phase 1b Monotherapy: Duration of Response (DOR) Per RECIST v1.1
DOR is defined as the time from first onset of response (CR or PR determined by the investigator per RECIST v1.1) that is subsequently confirmed until the onset of progressive disease or death from any cause, whichever comes first. Patients who were alive and progression-free at the time of data analysis were censored at the time of their last assessment for tumor response. DOR was estimated using the Kaplan-Meier method.
Measured: Up to approximately 24 months
Phase 1b Monotherapy: Progression-free Survival (PFS) Per RECIST v1.1
PFS defined as time from the first dose of study treatment until the first documentation by the investigator of disease progression per RECIST v1.1 or death from any cause, whichever comes first. Patients who were alive and progression-free at the time of data analysis were censored at the time of their last assessment for tumor response.
Measured: Up to approximately 24 months
Phase 1b Combination: PFS Per RECIST v1.1
PFS defined as time from the first dose of study treatment until the first documentation by the investigator of disease progression per RECIST v1.1 or death from any cause, whichever comes first. Patients who were alive and progression-free at the time of data analysis were censored at the time of their last assessment for tumor response.
Measured: Up to approximately 24 months
Phase 1b Combination: ORR Per RECIST v1.1
ORR was defined as the percentage of participants who achieved best overall response (BOR) of either complete response (CR) or partial response (PR) based on investigator assessment of tumor lesions per RECIST v1.1. The BOR was the best response documented from first dose until the end of study, first disease progression, death, or start of new anti-cancer therapy, whichever was earlier.
Measured: Up to approximately 24 months
Phase 1b Combination: DOR Per RECIST v1.1
DOR is defined as the time from first onset of response (CR or PR determined by the investigator per RECIST v1.1) that is subsequently confirmed until the onset of progressive disease or death from any cause, whichever comes first. Patients who were alive and progression-free at the time of data analysis were censored at the time of their last assessment for tumor response. DOR was estimated using the Kaplan-Meier method.
Measured: Up to approximately 24 months
Phase 1a Monotherapy: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of FPA150
FPA150 concentration in serum was determined using an enzyme linked immunosorbent assay (ELISA) method and the PK parameters were derived from serum FPA150 concentration-time data using non-compartment analysis.
Measured: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
Phase 1a Monotherapy: Time to Reach Maximum Serum Concentration (Tmax) of FPA150
Measured: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
Phase 1a Monotherapy: Maximum Serum Concentration (Cmax) of FPA150
Measured: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
Phase 1a Monotherapy: Trough Serum Concentration (Ctrough) of FPA150
Measured: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
Phase 1a Monotherapy: Terminal Half-Life (T1/2) of FPA150
Measured: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
Phase 1b Monotherapy: AUClast of FPA150
Measured: Cycle 1 (one cycle = 21 days) day 1 pre-dose, day 1 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks)
Phase 1b Monotherapy: Time to Reach Cmax of FPA150
Measured: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks
Phase 1b Monotherapy: Cmax of FPA150
Measured: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks
Phase 1b Monotherapy: Cthrough of FPA150
Measured: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks
Phase 1b Monotherapy: T1/2 of FPA150 in Days
Measured: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2018
- Study start27 Mar 2018
- Primary completion21 Apr 2021
- Study completion21 Apr 2021
Why it stopped: The Sponsor terminated the study for reasons unrelated to safety.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm trial with multiple cohorts
- Masking
- None (open label)
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Five Prime Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03514121
- Sponsor's protocol ID
- FPA150-001
- Acronym
- FPA150-001
- Status last verified
- Jan 2022
- First submitted
- 27 Mar 2018
- Last updated
- 22 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1a/1b Study of FPA150, an Anti-B7-H4 Antibody, in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03514121
- Acronym / sponsor ID
- FPA150-001 / FPA150-001
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The Sponsor terminated the study for reasons unrelated to safety.
- Enrolment
- 95 participants (actual)
- Lead sponsor
- Five Prime Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 27 Mar 2018 (actual)
- Primary completion
- 21 Apr 2021 (actual)
- Study completion
- 21 Apr 2021 (actual)
- First posted
- 2 May 2018 (actual)
- Results
- Posted 22 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a Phase 1a/1b open-label, multicenter study to evaluate the dosing, safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of FPA150 as monotherapy and in combination with pembrolizumab, an anti-PD1 antibody, in patients with advanced solid tumors.
This study includes a Phase 1a FPA150 Monotherapy Dose Escalation, Phase 1a Monotherapy Dose Exploration, Phase 1a combination Safety Lead-in (FPA150 + pembrolizumab), a Phase 1b FPA150 Monotherapy Dose Expansion, and a Phase 1b combination Dose Expansion (FPA150 + pembrolizumab).
The Phase 1a Monotherapy Dose Escalation will include an initial accelerated titration design followed by a standard 3+3 dose escalation design until the MTD and/or RD for Phase 1b is determined. The Phase 1a combination Safety Lead-In will start enrolling once the FPA150 monotherapy RD is identified in Phase 1a monotherapy dose escalation and will continue until the FPA150 MTD/RD in combination is identified. Phase 1a FPA150 monotherapy Dose Exploration may include cohorts that may enroll beyond 3 patients whose tumors express high levels of B7-H4 protein and/or have varying levels of B7H4 expression including low (<10% IHC 2+ or 3+ scores) or no expression on their tumor cells (up to 20 additional patients across all dose levels) to further evaluate safety, PK, pharmacodynamics, and clinical activity at that dose (to be conditional upon the dose level clearing DLT criteria).
Phase 1b will be the Dose Expansion (monotherapy and combination) portion of the study.
Enrollment into Phase 1b Dose Expansion will begin after identification of the MTD and/or RD in Phase 1a (monotherapy and Safety Lead-in). Preliminary efficacy will be evaluated in Phase 1b in planned expansion cohorts that include patients with specific tumor types that are B7-H4+ advanced solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm trial with multiple cohorts
| Arm | Type | Receives |
|---|---|---|
| Phase 1a dose escalation/1b dose expansion | Experimental | Biological: FPA150, Biological: PembrolizumabThe study consists of Phase 1a dose escalation, Phase 1a dose exploration, Phase 1a combination safety-lead-in and Phase 1b dose expansion |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- All Inclusion Criteria for Phase 1a (Exception: Phase 1a Inclusion Criterion #1).
- Positive for B7-H4 expression in an archival or fresh tumor sample as evaluated by an accompanying validated central laboratory IHC assay. Archival tissue for patients enrolled in Cohort 1b1 (Breast Cancer) must be within 24 months prior to pre-screening.
- History of other malignancy is permitted provided it has been definitively treated with no evidence of recurrence within the past 2 years (Exception: Definitively treated non-melanoma skin cancer, lobular cancer in situ, and cervical cancer in situ within 2 years are permitted). Cohort Specific Phase 1b Criteria (monotherapy and combination therapy)
- Histologically or cytologically confirmed metastatic TNBC
- At least two prior lines of systemic chemotherapy with at least one being administered in the metastatic setting
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FPA150A monoclonal antibody against B7-H4 | Biological | Phase 1a dose escalation/1b dose expansion |
| PembrolizumabAn anti-PD1 antibody | Biological | Phase 1a dose escalation/1b dose expansion |
Primary outcome
Phase 1a Monotherapy: Number of Participants Experiencing Grade 3 and Grade 4 Adverse Events (AEs)
Time frame: From day 1 up to 28 days after last dose (median [min, max] treatment duration= 9.143 [3.00, 52.00] weeks)
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
Phase 1a Monotherapy: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
Time frame: Up to 21 days
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
Phase 1a Monotherapy: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Time frame: From day 1 up to 28 days after last dose (median [min, max] treatment duration= 9.143 [3.00, 52.00] weeks)
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.
Phase 1b Monotherapy: Number of Participants Experiencing AEs
Time frame: From day 1 up to 28 days after last dose (median [min, max] treatment duration= 6.35 [3.00, 108.14] weeks)
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.
Phase 1a Combination Safety Lead-In & Phase 1b Combination: Number of Participants Experiencing AEs
Time frame: From day 1 up to 28 days after last dose (median [min, max] treatment duration= 12.00 [6.00, 36.43] weeks)
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.
Phase 1a Combination Safety Lead-In & Phase 1b Combination: Number of Participants Experiencing Grade 3 and Grade 4 AEs
Time frame: From day 1 up to 28 days after last dose (median [min, max] treatment duration= 12.00 [6.00, 36.43] weeks)
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.
19 secondary outcomes
Phase 1a Monotherapy: Number of Participants With ADAs to FPA150
Time frame: 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
Time frame: Cycle 1 day 1 pre-dose (baseline)
Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 Postbaseline
Time frame: 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)
Time frame: Up to approximately 24 months
Phase 1b Monotherapy: Duration of Response (DOR) Per RECIST v1.1
Time frame: Up to approximately 24 months
Phase 1b Monotherapy: Progression-free Survival (PFS) Per RECIST v1.1
Time frame: Up to approximately 24 months
Phase 1b Combination: PFS Per RECIST v1.1
Time frame: Up to approximately 24 months
Phase 1b Combination: ORR Per RECIST v1.1
Time frame: Up to approximately 24 months
Phase 1b Combination: DOR Per RECIST v1.1
Time frame: Up to approximately 24 months
Phase 1a Monotherapy: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of FPA150
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
Phase 1a Monotherapy: Time to Reach Maximum Serum Concentration (Tmax) of FPA150
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
Phase 1a Monotherapy: Maximum Serum Concentration (Cmax) of FPA150
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
Phase 1a Monotherapy: Trough Serum Concentration (Ctrough) of FPA150
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
Phase 1a Monotherapy: Terminal Half-Life (T1/2) of FPA150
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
Phase 1b Monotherapy: AUClast of FPA150
Time frame: Cycle 1 (one cycle = 21 days) day 1 pre-dose, day 1 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks)
Phase 1b Monotherapy: Time to Reach Cmax of FPA150
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks
Phase 1b Monotherapy: Cmax of FPA150
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks
Phase 1b Monotherapy: Cthrough of FPA150
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks
Phase 1b Monotherapy: T1/2 of FPA150 in Days
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
18 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing FPA150 and Pembrolizumab in people with Breast Cancer and Ovarian Cancer, run by Five Prime Therapeutics, Inc. at 18 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1a Monotherapy: Number of Participants Experiencing Grade 3 and Grade 4 Adverse Events (AEs) (time frame: From day 1 up to 28 days after last dose (median [min, max] treatment duration= 9.143 [3.00, 52.00] weeks)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2024.