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FPA150 in Patients With Advanced Solid Tumors (FPA150-001)

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ClinicalTrials.gov Identifier: NCT03514121
Recruitment Status : Recruiting
First Posted : May 2, 2018
Last Update Posted : July 24, 2019
Sponsor:
Information provided by (Responsible Party):
Five Prime Therapeutics, Inc.

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Ovarian Cancer Endometrial Cancer Advanced Solid Tumors Biological: FPA150 Biological: Pembrolizumab Early Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 278 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Single arm trial with multiple cohorts
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1a/1b Study of FPA150, an Anti-B7-H4 Antibody, in Patients With Advanced Solid Tumors
Actual Study Start Date : March 27, 2018
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2024


Arm Intervention/treatment
Experimental: Phase 1a dose escalation/1b dose expansion
The study consists of Phase 1a dose escalation, Phase 1a dose exploration, Phase 1a combination safety-lead-in and Phase 1b dose expansion
Biological: FPA150
A monoclonal antibody against B7-H4

Biological: Pembrolizumab
An anti-PD1 antibody




Primary Outcome Measures :
  1. 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 ]
    Tolerability

  2. For Phase 1a dose escalation, dose exploration and combination safety lead-in the number of participants with adverse events as assessed by the latest version of CTCAE [ Time Frame: Through study completion, an average of 24 weeks ]
    Safety

  3. For Phase 1b, number of participants with adverse events as assessed by the latest version of CTCAE at the maximum tolerated dose (MTD) and/or recommended dose (RD) of FPA150 [ Time Frame: Through study completion, average 24 weeks ]
    Safety


Secondary Outcome Measures :
  1. Area under serum concentration-time curve of FPA150 in day*µg/mL [ Time Frame: Through study completion, an average of 24 weeks ]
    Pharmacokinetic profile FPA150

  2. Maximum serum concentration of FPA150 in µg/mL [ Time Frame: Through study completion, an average of 24 weeks ]
    Pharmacokinetic Profile FPA150

  3. Trough serum concentration of FPA150 in µg/mL [ Time Frame: Through study completion, an average of 24 weeks ]
    Pharmacokinetic Profile FPA150

  4. Clearance of FPA150 in mL/day/kg [ Time Frame: Through study completion, an average of 24 weeks ]
    Pharmacokinetic Profile FPA150

  5. Terminal Half-Life of FPA150 in day [ Time Frame: Through study completion, an average of 24 weeks ]
    Pharmacokinetic Profile FPA150

  6. Volume of distribution (mL/kg) of FPA150 [ Time Frame: Through study completion, an average of 24 weeks ]
    Pharmacokinetic Profile FPA150

  7. Incidence of treatment emergent anti-FPA150 antibody response (levels in serum) [ Time Frame: Through study completion, an average of 24 weeks ]
    Immunogenicity FPA150


Other Outcome Measures:
  1. For Phase 1b, to evaluate the overall response rate (ORR) defined as the total number of patients with complete response (CR) or partial response (PR) per RECIST v1.1 divided by the total number of patients who are evaluable for a response [ Time Frame: Through study completion, an average of 24 weeks ]
    Efficacy



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03514121


Contacts
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Contact: Neyssa Marina (866) 588-3796 FPA150-001@fiveprime.com
Contact: Stefanie Sun (866) 588-3796 FPA150-001@fiveprime.com

Locations
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United States, Arizona
Honor Health Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Jasgit Sachdev, MD         
United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Kamalesh Sankhala, MD         
UCLA Recruiting
Los Angeles, California, United States, 90095
Contact: Zev A Wainberg, MD         
Sarcoma Oncology Research Center Recruiting
Santa Monica, California, United States, 90403
Contact: Sant P Chawla, MD         
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06520
Contact: Patricia LoRusso, DO         
United States, Illinois
Orchard Healthcare Research Inc. Recruiting
Skokie, Illinois, United States, 60077
Contact: Ira Oliff, MD         
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Amy M. Weise, DO         
United States, Oklahoma
Stephenson Cancer Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Debra Richardson, MD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Todd Bauer, MD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Shubham Pant, MD         
South Texas Accelerated Research Therapeutics Recruiting
San Antonio, Texas, United States, 78229
Contact: Amita Patnaik, MD         
United States, Utah
Utah Cancer Specialists Recruiting
Salt Lake City, Utah, United States, 84106
Contact: Justin Call, MD         
United States, Washington
Medical Oncology Associates, PS Recruiting
Spokane, Washington, United States, 99208
Contact: Arvind Chaudhry, MD         
Korea, Republic of
National Cancer Center Recruiting
Gyeonggi-do, Korea, Republic of, 10408
Contact: Keun Seok Lee, MD         
Seoul National University Bundang Hospital Recruiting
Gyeonggi-do, Korea, Republic of, 13620
Contact: Jee Hyun Kim, MD         
Severance Hospital Recruiting
Seoul, Korea, Republic of, 03722
Contact: Joo Hyuk Sohn, MD         
ASAN Medical Center Recruiting
Seoul, Korea, Republic of, 05505
Contact: Sung Bae Kim, MD         
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 06351
Contact: Yeon Hee Park, MD         
Sponsors and Collaborators
Five Prime Therapeutics, Inc.

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Responsible Party: Five Prime Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03514121     History of Changes
Other Study ID Numbers: FPA150-001
First Posted: May 2, 2018    Key Record Dates
Last Update Posted: July 24, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Endometrial Neoplasms
Neoplasms
Neoplasms by Site
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Neoplasms
Uterine Diseases
Pembrolizumab
Antibodies
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents