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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 : Recruiting
First Posted : October 9, 2015
Last Update Posted : October 19, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Part 1 MELANOMA SCCHN OVCA SARCOMA OTHER SOLID TUMORS Part 1 and 2 NSCLC UROTHELIAL CARCINOMA Drug: PF-06801591 Phase 1

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : February 10, 2016
Estimated Primary Completion Date : March 4, 2019
Estimated Study Completion Date : November 11, 2020


Arm Intervention/treatment
Experimental: Arm 1 PF-06801591
0.5 mg/kg IV every 21 days (Part 1)
Drug: PF-06801591
IV every 21 days (Part 1)

Experimental: Arm 2 PF-06801591
1.0 mg/kg IV every 21 days (Part 1)
Drug: PF-06801591
IV every 21 days (Part 1)

Experimental: Arm 3 PF-06801591
3.0 mg/kg IV every 21 days (Part 1)
Drug: PF-06801591
IV every 21 days (Part 1)

Experimental: Arm 4 PF-06801591
10 mg/kg IV every 21 days (Part 1)
Drug: PF-06801591
IV every 21 days (Part 1)

Experimental: Arm 5 PF-06801591
300 mg SC every 28 days (Part 1 and 2)
Drug: PF-06801591
300 mg SC every 28 days (Part 1 and 2)




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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).


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. Evaluate overall survival [ Time Frame: Approximately 2 years ]
    Median time to death, proportion of patients alive at 6 months, 1 year, and 2 years.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT02573259


Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

  Show 93 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02573259     History of Changes
Other Study ID Numbers: B8011001
2016-003314-27 ( EudraCT Number )
First Posted: October 9, 2015    Key Record Dates
Last Update Posted: October 19, 2018
Last Verified: October 2018

Keywords provided by Pfizer:
efficacy
safety
pharmacokinetics
pharmacodynamics
open label
dose response
multiple ascending dose
immunogenicity
recommended phase 2 dose
subcutaneous

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Melanoma
Sarcoma
Head and Neck Neoplasms
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Connective and Soft Tissue