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Study Of OX40 Agonist PF-04518600 Alone And In Combination With 4-1BB Agonist PF-05082566

This study is currently recruiting participants.
Verified November 2017 by Pfizer
Sponsor:
ClinicalTrials.gov Identifier:
NCT02315066
First Posted: December 11, 2014
Last Update Posted: November 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Pfizer
  Purpose
To assess the safety and tolerability at increasing dose levels of PF-04518600 alone or in combination wtih PF-05082566 in patients with select advanced or metastatic carcinoma in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.

Condition Intervention Phase
Neoplasms Drug: PF-04518600 Drug: PF-04518600 plus PF-05082566 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: None (Open Label)
Masking Description:
Open-label
Primary Purpose: Treatment
Official Title: A Phase 1, Open-label, Dose Escalation Study Of Pf-04518600 As A Single Agent And In Combination With Pf-05082566 In Patients With Selected Locally Advanced Or Metastatic Cancers

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of participants with Dose-limiting toxicities (DLT) [Dose Escalation] [ Time Frame: Day 1 up to Day 28 ]
    First and second cycle DLTs in order to determine maximum tolerated dose

  • Overall safety profile [Dose Expansion] [ Time Frame: Day 1 up to Day 28 ]
    Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any laboratory abnormalities.


Secondary Outcome Measures:
  • Incidence of anti-drug antibodies and neutralization assays [ Time Frame: 0 hr on Day 1 Cycles 1 to 4, 7 and every other cycle ]
    Number of participants with the presence of anti-PF-04518600 antibodies and neutralization assays

  • Number of participants with objective response [ Time Frame: Baseline, every 6 weeks (Part 1) or 8 weeks (Part 2) until disease progression or unacceptable toxicity ]
    Number of participants with objective response based on assessment of progression free survival (PFS), time to progression (TTP), duration of stable disease (SD), duration of response (DR) according to RECIST version 1.1 and irRECIST and overall survival (OS).

  • Unbound (free) cell surface OX40 in peripheral blood [ Time Frame: 0 hr and scheduled timepoints post dose on Cycles 1 to 3, then 0hr on cycles 4 and 7 ]
    Levels of free OX40 receptor expressed on T cells in peripheral blood after dosing with PF 04518600 alone or in combination with PF 05082566.

  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0 hr and scheduled timepoints post dose on Cycles 1 to 6, then 0hr on every cycle ]
    Cmax will be calculated for PF-04518600 and PF-05082566

  • Area under the concentration versus time curve (AUCt) [ Time Frame: 0 hr and scheduled timepoints post dose on Cycles 1 to 6, then 0hr on every cycle ]
    Area under the plasma concentration versus time curve will be calculated for PF-04518600 and PF-05082566


Estimated Enrollment: 210
Actual Study Start Date: April 23, 2015
Estimated Study Completion Date: July 21, 2020
Estimated Primary Completion Date: November 25, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PF-04518600
OX40 agonist
Drug: PF-04518600
Part A1 - PF-04518600 will be administered intravenously every 14 days in cohorts of 2 or more patients starting at a dose of 0.01 mg/kg. Increases in dose will continue until MTD is determined
Drug: PF-04518600
Part A2 - patients with hepatocellular carcinoma will be randomized to receive treatment with PF-04518600 at various doses administered intravenously
Experimental: PF-04518600 plus PF-05082566
OX40 (CD134) agonist plus 4-1BB (CD137) agonist
Drug: PF-04518600 plus PF-05082566
Part B1 -In cohorts of 2 or more patients, PF-04518600 will be administered intravenously every 2 weeks starting at a dose of 0.1 mg/kg and PF-05082566 will be administered intravenously 4 weeks starting at a dose of 20 mg. Increases in dose will continue until MTD is determined.
Drug: PF-04518600 plus PF-05082566
Part B2 - patients with select tumor types (ocular melanoma, cutaneous/acral melanoma or non-small cell lung cancer) will be treated at dose levels based on the OBD selected in Part 1.

  Eligibility

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Part A1 only: Patients with histological or cytological diagnosis of HNSCC, HCC, melanoma, or clear cell RCC who progressed on or are intolerant to standard therapy, for which no standard therapy is available or who decline standard therapy.
  • Part A2 only: Patients with histological or cytological diagnosis of HCC who have had 0 to 2 prior lines of systemic therapy (progressed or intolerant to approved HCC standard of care treatment).
  • Part B1 only: Patients with histological or cytological diagnosis of NSCLC, HNSCC, melanoma, urothelial bladder carcinoma (including renal pelvis, ureters, urinary bladder, and urethra), gastric or squamous cell carcinoma of the uterine cervix who progressed on or are intolerant to standard therapy, for which no standard therapy is available, or who decline standard therapy.
  • Part B2

Arm 1 only:

  1. Ocular melanoma; and have received no more than one line of systemic therapy for metastatic disease. Patients must not have received immune modifying agents (eg. anti PD-L1, anti PD-1, anti CTLA4, TNF agonist, etc.) for metastatic disease, or
  2. Cutaneous/acral melanoma; and have 1) only previously received systemic therapy for advanced/metastatic disease with the following therapies: BRAF and MEK inhibitors, anti PD-L1, anti PD-1, or anti-CTLA4 and 2) have received checkpoint inhibitor (anti PD-L1, anti PD-1, or anti-CTLA4) based treatment as most recent line of therapy on which disease progressed, as long as progression did not occur in the first 3 months of receiving checkpoint inhibitor treatment.

Arm 2 only:

  • Histological or cytological diagnosis of NSCLC. Patients must have 1) previously received prior anti-PD-L1 or anti-PD-1 mAb as most recent therapy, AND 2) did not have progressive disease as best overall response on recent PD-L1/PD-1 therapy (ie, stable disease 3 months, PR, or CR), AND 3) who subsequently progressed on anti-PD-L1 or anti-PD-1 mAb.
  • Performance Status of 0 or 1 - Adequate bone marrow, kidney and liver function

Exclusion Criteria:

  • Brain metastases requiring steroids
  • Major surgery, radiation therapy, or systemic anti-cancer therapy within 4 weeks of study treatment start (6 weeks for mitomycin C or nitrosoureas)
  • Active and clinically significant bacterial, fungal, or viral infection
  • History of active autoimmune disorders
  • History of immune-mediated adverse events requiring immunosuppressive therapy or were grade 3 or higher related to prior immune-modulatory therapy
  • Prior treatment with an OX40 agonist and 4-1BB agonist (for Part B1/B2)
  • Prior anthracycline treatment and at risk of cardiac failure (New York Heart Association Class 2)
  Contacts and Locations
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): NCT02315066


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

  Show 36 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02315066     History of Changes
Other Study ID Numbers: B0601002
2014-004107-75 ( EudraCT Number )
B0601002 ( Other Identifier: Alias Study Number )
First Submitted: December 4, 2014
First Posted: December 11, 2014
Last Update Posted: November 7, 2017
Last Verified: November 2017

Keywords provided by Pfizer:
solid tumors
tumors
neoplasm metastasis
liver cancer
clear cell renal cell carcinoma
kidney cancer
head and neck cancer
cervical cancer
cancer of the cervix
gastric cancer
stomach cancer
non small cell lung cancer
lung cancer
bladder cancer
Immunotherapy
PF-04518600
PF-05082566
Phase 1
hepatocellular carcinoma
HCC
ocular melanoma
melanoma
RCC
head and neck squamous cell carcinoma
HNSCC
NSCLC
urothelial bladder carcinoma
OX40
4-1BB

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs