Clinical Trials /

FPA150 in Patients With Advanced Solid Tumors

NCT03514121

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Endometrial Carcinoma
  • Fallopian Tube Carcinoma
  • Malignant Ovarian Epithelial Tumor
  • Malignant Solid Tumor
  • Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: FPA150 in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1a/1b Study of FPA150, an Anti-B7-H4 Antibody, in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: FPA150-001
  • NCT ID: NCT03514121

Conditions

  • Breast Cancer
  • Ovarian Cancer
  • Endometrial Cancer
  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
FPA150Phase 1a dose escalation/1b dose expansion
PembrolizumabPhase 1a dose escalation/1b dose expansion

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1a dose escalation/1b dose expansionExperimentalThe study consists of Phase 1a dose escalation, Phase 1a dose exploration, Phase 1a combination safety-lead-in and Phase 1b dose expansion
  • FPA150
  • Pembrolizumab

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
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:For Phase 1a dose escalation, to determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of FPA150
Time Frame:Through study completion, an average of 24 weeks
Safety Issue:
Description:Tolerability

Secondary Outcome Measures

Measure:Area under serum concentration-time curve of FPA150 in day*µg/mL
Time Frame:Through study completion, an average of 24 weeks
Safety Issue:
Description:Pharmacokinetic profile FPA150
Measure:Maximum serum concentration of FPA150 in µg/mL
Time Frame:Through study completion, an average of 24 weeks
Safety Issue:
Description:Pharmacokinetic Profile FPA150
Measure:Trough serum concentration of FPA150 in µg/mL
Time Frame:Through study completion, an average of 24 weeks
Safety Issue:
Description:Pharmacokinetic Profile FPA150
Measure:Clearance of FPA150 in mL/day/kg
Time Frame:Through study completion, an average of 24 weeks
Safety Issue:
Description:Pharmacokinetic Profile FPA150
Measure:Terminal Half-Life of FPA150 in day
Time Frame:Through study completion, an average of 24 weeks
Safety Issue:
Description:Pharmacokinetic Profile FPA150
Measure:Volume of distribution (mL/kg) of FPA150
Time Frame:Through study completion, an average of 24 weeks
Safety Issue:
Description:Pharmacokinetic Profile FPA150
Measure:Incidence of treatment emergent anti-FPA150 antibody response (levels in serum)
Time Frame:Through study completion, an average of 24 weeks
Safety Issue:
Description:Immunogenicity FPA150
Measure:Pharmacodynamic profile of FPA150
Time Frame:Through study completion, an average of 24 weeks
Safety Issue:
Description:Biomarker analysis of the fibroblast growth factor receptor (FGFR) pathway in blood

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Five Prime Therapeutics, Inc.

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