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A Dose Escalation Study Of PF-06801591 In Melanoma, Head And Neck Cancer (SCCHN), Ovarian, Sarcoma, Non-Small Cell Lung Cancer, Urothelial Carcinoma or Other Solid Tumors

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ClinicalTrials.gov Identifier: NCT02573259
Recruitment Status : Completed
First Posted : October 9, 2015
Last Update Posted : January 28, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE October 6, 2015
First Posted Date  ICMJE October 9, 2015
Last Update Posted Date January 28, 2021
Actual Study Start Date  ICMJE February 10, 2016
Actual Primary Completion Date November 19, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 26, 2017)
  • Percentage of participants with Dose-limiting toxicities (DLT) [ Time Frame: 90 days ]
    A DLT is any of a predefined set of unacceptable adverse events that are observed and that are at least possibly related to the investigational agent(s) OR a DLT is any of a predefined set of unacceptable adverse events (AE), regardless of cause.
  • Overall Safety Profile [ Time Frame: approximately 2 years ]
    Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events (AE) and any laboratory abnormalities.
  • Estimate clinical efficacy [ Time Frame: Baseline and every 8-12 weeks through time of confirmed disease progression, unacceptable toxicity, or through study completion (approximately 2 years). ]
    Objective tumor response, as assessed using the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 criteria, immune-related RECIST (irRECIST).
Original Primary Outcome Measures  ICMJE
 (submitted: October 8, 2015)
  • Percentage of participants with Dose-limiting toxicities (DLT) [ Time Frame: Day 1 up to day 21 ]
    A DLT is any of a predefined set of unacceptable adverse events that are observed and that are at least possibly related to the investigational agent(s) OR a DLT is any of a predefined set of unacceptable adverse events, regardless of cause.
  • Overall Safety Profile [ Time Frame: Day 1 up to Day 21 ]
    Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any laboratory abnormalities.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2017)
  • Area under the concentration versus time curve (AUCt) [ Time Frame: Baseline through end of treatment, an approximate average of 4 months ]
    AUCt will be calculated for PF- 06801591
  • Incidence of anti drug antibodies (ADA) [ Time Frame: Baseline through end of treatment, an approximate average of 4 months ]
    Incidence of anti drug antibodies (ADA) and neutralizing antibodies (NAb) against PF-06801591.
  • Percentage of Receptor Occupancy (RO) [ Time Frame: 0hr at Baseline and through end of treatment, an approximate average of 4 months ]
    Percentage RO of PF-06801591 in circulating T cells over time following PF-06801591 administration.
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0hr at Baseline and through end of treatment; an approximate average of 4 months ]
    Cmax will be calculated for PF-06801591
  • Evaluate preliminary anti-tumor activity of PF-06801591 [ Time Frame: Baseline and every 8-12 weeks through time of confirmed disease progression, unacceptable toxicity, or through study completion (approximately 2 years). ]
    Time to event endpoints based on RECIST and irRECIST, including time to response (TTR) and time to progression (TTP) as well as progression free survival (PFS) and immune-related (ir) PFS (irPFS) as appropriate, duration of stable disease (DOSD) and irDOSD as appropriate, and duration of response (DOR) and irDOR as appropriate.
  • Evaluate overall survival [ Time Frame: Approximately 2 years ]
    Median time to death, proportion of patients alive at 6 months, 1 year, and 2 years.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2015)
  • Area under the concentration versus time curve (AUCt) [ Time Frame: 0hr on Day1, Day 2, Day 8, Day 15, Cycles 2 and 3 Day 1 and Cycle 4 days 1 and 15 and Cycle 5 Day 1 and Day 1 of each subsequent (21 day) cycle through study completion an average of 4 months ]
    AUCt will be calculated for PF- 06801591
  • Incidence of anti drug antibodies (ADA) [ Time Frame: 0 hr on Day 1 Cycles 2 (Day 42) and 4 (Day 84), and every other (21 day) cycle (42 days) through study completion an average of 4 months ]
    Incidence of anti drug antibodies (ADA) and neutralizing antibodies (NAb) against PF-06801591.
  • Number of patients with ORR (Objective Response Rate) (RECIST) [ Time Frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months ]
    Objective tumor response, as assessed using the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 criteria
  • Percentage of Receptor Occupancy [ Time Frame: 0hr on Day1, Day 2, Day 8, Day 15, Cycles 2 and 3 Day 1 (Days 22 and 43) and Cycle 4 days 1 (Day 85) and 15 (Day 100) and Cycle 5 Day 1 (Day 106) ]
    Percentage RO of PF-06801591 in circulating T cells over time following PF-06801591 administration.
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0hr on Day1, Day 2, Day 8, Day 15, Cycles 2 and 3 Day 1 (Days 22 and 43) and Cycle 4 days 1 (Day 85) and 15 (Day 100) and Cycle 5 Day 1 (Day 106) and every 21 days after Cycle 5 Day 1 through study completion an average of 4 months ]
    Cmax will be calculated for PF-06801591
  • Number of patients with ORR (Objective Response Rate)(irRECIST) [ Time Frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months ]
    Objective tumor response, as assessed using immune related RECIST (irRECIST) criteria
  • Number of patients with ORR (Objective Response Rate) (Lymphoma Response) [ Time Frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months ]
    Objective tumor response, as assessed using Lymphoma Response Criteria
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Dose Escalation Study Of PF-06801591 In Melanoma, Head And Neck Cancer (SCCHN), Ovarian, Sarcoma, Non-Small Cell Lung Cancer, Urothelial Carcinoma or Other Solid Tumors
Official Title  ICMJE A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND EXPANSION STUDY OF PF-06801591 IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC MELANOMA, SQUAMOUS CELL HEAD AND NECK CANCER, OVARIAN CANCER, SARCOMA, NON-SMALL CELL LUNG CANCER, UROTHELIAL CARCINOMA OR OTHER SOLID TUMORS.
Brief Summary Protocol B8011001 is a Phase 1, open-label, multi-center, multiple-dose, dose escalation and expansion, safety, pharmacokinetics (PK), and pharmacodynamics (PD) study of PF-06801591 in previously treated adult patients with locally advanced or metastatic melanoma, SCCHN, ovarian carcinoma, sarcoma, NSCLC, urothelial carcinoma or other solid tumors. This is a 2 Part study whereby the safety and tolerability of increasing dose levels of intravenous (IV) or subcutaneous (SC) PF-06801591 was assessed in Part 1. Part 2 expansion is designed to further evaluate the safety and efficacy of SC PF-06801591 in patients with NSCLC or urothelial carcinoma as well as confirm the recommended Phase 2 dose.
Detailed Description

Protocol B8011001 is a Phase 1, two part, open-label, multi center, multiple-dose, safety, efficacy, PK, and PD study of PF-06801591 administered intravenously (IV) or subcutaneous (SC) in previously treated adult patients with locally advanced or metastatic melanoma, squamous cell carcinoma head and neck (SCCHN), ovarian carcinoma, sarcoma, non-small cell lung carcinoma (NSCLC), urothelial carcinoma or other solid tumors.

The first part of the study, Part 1 dose escalation, was designed to assess the safety and tolerability of increasing dose levels of IV or SC administered PF-06801591 to establish the maximum tolerated dose (MTD) using a modified Toxicity Probability Interval (mTPI) design. Part 2 expansion is designed to further evaluate the safety and efficacy of 300 mg of PF-06801591 administered SC once every 4 weeks in patients with NSCLC or urothelial carcinoma as well as confirm the recommended Phase 2 dose (RP2D). Part 1 enrollment has completed, enrollment will only be allowed for Part 2.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Part 1
  • MELANOMA
  • SCCHN
  • OVCA
  • SARCOMA
  • OTHER SOLID TUMORS
  • Part 1 and 2
  • NSCLC
  • UROTHELIAL CARCINOMA
Intervention  ICMJE
  • Drug: PF-06801591
    IV every 21 days (Part 1)
  • Drug: PF-06801591
    300 mg SC every 28 days (Part 1 and 2)
Study Arms  ICMJE
  • Experimental: Arm 1 PF-06801591
    0.5 mg/kg IV every 21 days (Part 1)
    Intervention: Drug: PF-06801591
  • Experimental: Arm 2 PF-06801591
    1.0 mg/kg IV every 21 days (Part 1)
    Intervention: Drug: PF-06801591
  • Experimental: Arm 3 PF-06801591
    3.0 mg/kg IV every 21 days (Part 1)
    Intervention: Drug: PF-06801591
  • Experimental: Arm 4 PF-06801591
    10 mg/kg IV every 21 days (Part 1)
    Intervention: Drug: PF-06801591
  • Experimental: Arm 5 PF-06801591
    300 mg SC every 28 days (Part 1 and 2)
    Intervention: Drug: PF-06801591
Publications * Johnson ML, Braiteh F, Grilley-Olson JE, Chou J, Davda J, Forgie A, Li R, Jacobs I, Kazazi F, Hu-Lieskovan S. Assessment of Subcutaneous vs Intravenous Administration of Anti-PD-1 Antibody PF-06801591 in Patients With Advanced Solid Tumors: A Phase 1 Dose-Escalation Trial. JAMA Oncol. 2019 Jul 1;5(7):999-1007. doi: 10.1001/jamaoncol.2019.0836.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 15, 2019)
147
Original Estimated Enrollment  ICMJE
 (submitted: October 8, 2015)
180
Actual Study Completion Date  ICMJE November 19, 2020
Actual Primary Completion Date November 19, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria (Part 2 Only):

  • Histological or cytological diagnosis of locally advanced or metastatic NSCLC or urothelial carcinoma who have progressed on or were intolerant to standard of care systemic therapy, or for whom standard of care systemic therapy was refused (refusal must be documented) or unavailable.
  • No prior treatment with anti-PD-1 or anti-PD-L1 therapy.
  • NSCLC patients whose tumor is not known to have ALK or EGFR mutations must have progressed on or after no more than 1 prior line of platinum-containing systemic therapy or were intolerant or refused standard of care systemic therapy.
  • NSCLC patients whose tumor is known to have ALK or EGFR mutation must have received prior systemic therapies that only include 1 or more lines of ALK or EGFR targeting drugs and chemotherapy limited to 1 line of a platinum-based regimen and they must have progressed on or after both types of therapies.
  • Urothelial carcinoma patients must have received up to 2 lines of prior systemic therapy and progressed on or after, experienced disease recurrence within 12 months of neoadjuvant or adjuvant treatment, were intolerant to, ineligible or refused platinum-containing systemic therapy. If urothelial cancer patients are treatment naïve and eligible for platinum-containing systemic therapy but are refusing platinum chemotherapy, they must also be documented to have previous PD-L1 high status.
  • Provide archived tumor tissue sample taken within the past 2 years or provide a fresh tumor biopsy sample.
  • At least one measurable lesion as defined by RECIST version 1.1.
  • Adequate renal, liver, thyroid and bone marrow function.
  • Performance status 0 or 1.
  • Patient is capable of receiving study treatment for at least 8 weeks.

Exclusion Criteria (Part 2 Only)

  • Active brain or leptomeningeal metastases.
  • Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive therapy or prior allogeneic bone marrow or hematopoietic stem cell transplant.
  • Patients with a condition requiring systemic treatment with either corticosteroids (>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Patients with a history of interstitial lung disease, non-infectious pneumonitis, or active pulmonary tuberculosis. Those with active lung infections requiring treatment are also excluded.
  • History of Grade ≥3 immune mediated AE (including AST/ALT elevations that where considered drug related and cytokine release syndrome) that was considered related to prior immune modulatory therapy (eg, immune checkpoint inhibitors, co-stimulatory agents, etc.) and required immunosuppressive therapy.
  • Active hepatitis B or C, HIV/AIDS.
  • Other potentially metastatic malignancy within past 5 years.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   Korea, Republic of,   Malaysia,   Poland,   Russian Federation,   Ukraine,   United States
Removed Location Countries Singapore
 
Administrative Information
NCT Number  ICMJE NCT02573259
Other Study ID Numbers  ICMJE B8011001
2016-003314-27 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP