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.
Brief Title
FPA150 in Patients With Advanced Solid Tumors
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Breast Cancer
Ovarian Cancer
Endometrial Cancer
Advanced Solid Tumors
Eligibility Criteria
Inclusion Criteria (Phase 1a Monotherapy and Combination Therapy):
* 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
* AST and ALT \< 3× ULN (\<5ULN in patients with liver metastases)
* Bilirubin \< 1.5× ULN (except patients with Gilbert's syndrome, who must have total bilirubin \< 3 mg/dL)
* For Phase 1a Combination Safety Lead-in Patients ONLY:
* B7-H4 positive ovarian cancer
* or cytologically confirmed diagnosis of recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma that is refractory to existing therapy(ies) known to provide clinical benefit
* 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
Inclusion Criteria (Phase 1b monotherapy and combination):
* 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
* 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
Exclusion Criteria:
* 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
* For Cohort 1b1 only: Patients with HER2 positive disease
* 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
* AST and ALT \< 3× ULN (\<5ULN in patients with liver metastases)
* Bilirubin \< 1.5× ULN (except patients with Gilbert's syndrome, who must have total bilirubin \< 3 mg/dL)
* For Phase 1a Combination Safety Lead-in Patients ONLY:
* B7-H4 positive ovarian cancer
* or cytologically confirmed diagnosis of recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma that is refractory to existing therapy(ies) known to provide clinical benefit
* 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
Inclusion Criteria (Phase 1b monotherapy and combination):
* 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
* 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
Exclusion Criteria:
* 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
* For Cohort 1b1 only: Patients with HER2 positive disease
Inclusion Criteria
Inclusion Criteria (Phase 1a Monotherapy and Combination Therapy):
* 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
* AST and ALT \< 3× ULN (\<5ULN in patients with liver metastases)
* Bilirubin \< 1.5× ULN (except patients with Gilbert's syndrome, who must have total bilirubin \< 3 mg/dL)
* For Phase 1a Combination Safety Lead-in Patients ONLY:
* B7-H4 positive ovarian cancer
* or cytologically confirmed diagnosis of recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma that is refractory to existing therapy(ies) known to provide clinical benefit
* 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
Inclusion Criteria (Phase 1b monotherapy and combination):
* 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
* 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
* 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
* AST and ALT \< 3× ULN (\<5ULN in patients with liver metastases)
* Bilirubin \< 1.5× ULN (except patients with Gilbert's syndrome, who must have total bilirubin \< 3 mg/dL)
* For Phase 1a Combination Safety Lead-in Patients ONLY:
* B7-H4 positive ovarian cancer
* or cytologically confirmed diagnosis of recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma that is refractory to existing therapy(ies) known to provide clinical benefit
* 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
Inclusion Criteria (Phase 1b monotherapy and combination):
* 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
99 Years
Minimum Age
18 Years
NCT Id
NCT03514121
Org Class
Industry
Org Full Name
Five Prime Therapeutics, Inc.
Org Study Id
FPA150-001
Overall Status
Terminated
Phases
Early Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 1a/1b Study of FPA150, an Anti-B7-H4 Antibody, in Patients With Advanced Solid Tumors
Primary Outcomes
Outcome Description
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
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
Outcome Measure
Phase 1a Monotherapy: Number of Participants Experiencing Grade 3 and Grade 4 Adverse Events (AEs)
Outcome Time Frame
From day 1 up to 28 days after last dose (median [min, max] treatment duration= 9.143 [3.00, 52.00] weeks)
Outcome Description
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
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
Outcome Measure
Phase 1a Monotherapy: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
Outcome Time Frame
Up to 21 days
Outcome Description
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.
Outcome Measure
Phase 1a Monotherapy: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Outcome Time Frame
From day 1 up to 28 days after last dose (median [min, max] treatment duration= 9.143 [3.00, 52.00] weeks)
Outcome Description
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.
Outcome Measure
Phase 1b Monotherapy: Number of Participants Experiencing AEs
Outcome Time Frame
From day 1 up to 28 days after last dose (median [min, max] treatment duration= 6.35 [3.00, 108.14] weeks)
Outcome Description
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.
Outcome Measure
Phase 1a Combination Safety Lead-In & Phase 1b Combination: Number of Participants Experiencing AEs
Outcome Time Frame
From day 1 up to 28 days after last dose (median [min, max] treatment duration= 12.00 [6.00, 36.43] weeks)
Outcome Description
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.
Outcome Measure
Phase 1a Combination Safety Lead-In & Phase 1b Combination: Number of Participants Experiencing Grade 3 and Grade 4 AEs
Outcome Time Frame
From day 1 up to 28 days after last dose (median [min, max] treatment duration= 12.00 [6.00, 36.43] weeks)
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
From day 1 up to 28 days after last dose (median [min, max] treatment duration= 9.143 [3.00, 52.00] weeks)
Outcome Measure
Phase 1a Monotherapy: Number of Participants With ADAs to FPA150
Outcome Description
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.
Outcome Time Frame
Cycle 1 day 1 pre-dose (baseline)
Outcome Measure
Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 at Baseline
Outcome Description
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.
Outcome Time Frame
From day 1 up to 28 days after last dose (median [min, max] treatment duration= 6.35 [3.00, 108.14] weeks)
Outcome Measure
Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 Postbaseline
Outcome Description
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.
Outcome Time Frame
Up to approximately 24 months
Outcome Measure
Phase 1b Monotherapy: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Outcome Description
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.
Outcome Time Frame
Up to approximately 24 months
Outcome Measure
Phase 1b Monotherapy: Duration of Response (DOR) Per RECIST v1.1
Outcome Description
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.
Outcome Time Frame
Up to approximately 24 months
Outcome Measure
Phase 1b Monotherapy: Progression-free Survival (PFS) Per RECIST v1.1
Outcome Description
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.
Outcome Time Frame
Up to approximately 24 months
Outcome Measure
Phase 1b Combination: PFS Per RECIST v1.1
Outcome Description
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.
Outcome Time Frame
Up to approximately 24 months
Outcome Measure
Phase 1b Combination: ORR Per RECIST v1.1
Outcome Description
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.
Outcome Time Frame
Up to approximately 24 months
Outcome Measure
Phase 1b Combination: DOR Per RECIST v1.1
Outcome Description
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.
Outcome 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
Outcome Measure
Phase 1a Monotherapy: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of FPA150
Outcome 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
Outcome Measure
Phase 1a Monotherapy: Time to Reach Maximum Serum Concentration (Tmax) of FPA150
Outcome 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
Outcome Measure
Phase 1a Monotherapy: Maximum Serum Concentration (Cmax) of FPA150
Outcome 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
Outcome Measure
Phase 1a Monotherapy: Trough Serum Concentration (Ctrough) of FPA150
Outcome 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
Outcome Measure
Phase 1a Monotherapy: Terminal Half-Life (T1/2) of FPA150
Outcome 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)
Outcome Measure
Phase 1b Monotherapy: AUClast of FPA150
Outcome 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
Outcome Measure
Phase 1b Monotherapy: Time to Reach Cmax of FPA150
Outcome 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
Outcome Measure
Phase 1b Monotherapy: Cmax of FPA150
Outcome 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
Outcome Measure
Phase 1b Monotherapy: Cthrough of FPA150
Outcome 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
Outcome Measure
Phase 1b Monotherapy: T1/2 of FPA150 in Days
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
99
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sanjay Goel
Investigator Email
sgoel@montefiore.org
Investigator Phone
718-405-8404