Clinical trial NCT02179918: A Study Of 4-1BB Agonist PF-05082566 Plus PD-1 Inhibitor MK-3475 In Patients With Solid Tumors (B1641003/KEYNOTE-0036)
Official title: A PHASE 1B STUDY OF THE 4-1BB AGONIST PF-05082566 IN COMBINATION WITH THE PD-1 INHIBITOR MK-3475 IN PATIENTS WITH ADVANCED SOLID TUMORS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Advanced Solid Tumors
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2014-07-02
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: This is a safety, pharmacokinetic and pharmacodynamic study designed to estimate the maximum tolerated dose (MTD), and determine the Recommended Phase 2 Dose (RP2D) of PF-05082566, a 4-1BB agonist monoclonal antibody (mAb), in combination with MK-3475, a PD-1 inhibitor in patients with solid tumors.


Eligibility criteria: Inclusion Criteria:

* Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy which has progressed on standard therapy or for which no standard therapy is available.
* Measurable disease per RECIST v1.1.
* Adequate bone marrow, renal and liver functioning

Exclusion Criteria:

* CNS primary malignancies, active seizure disorder or spinal cord compression, or carcinomatous meningitis.
* History of any of the following toxicities associated with a prior immunotherapy:

  * Grade 3 immune mediated adverse event that was considered related to previous immunotherapy and required immune suppressive therapy;
  * Grade 2 hepatic function related adverse event that persisted more than 1 week, was considered related to immunotherapy, or required treatment discontinuation or immunosuppressive therapy
* Any of the following within the 12 months prior to registration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism.
* History of or known presence of extensive, disseminated/bilateral or Grade 3 or 4 interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, or pulmonary fibrosis, but not including a history of prior radiation pneumonitis. Patients with clinically significant lung disease requiring oxygen therapy (eg, COPD).

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLT) of PF-05082566 in Combination With MK-3475
timeFrame: First 2 cycles of treatment up to 24 months
Secondary outcomes:
measure: Number of Subjects With Serious Adverse Events (SAEs) and Treatment Emergent Adverse Events (TEAEs) by Maximum CTCAE Grade (All Causalities)
timeFrame: Baseline up to 90 days after the last dose of study drug, approximately 27 months
measure: Number of Participants With Serious Adverse Events (SAEs) and Treatment Emergent Adverse Events (TEAEs) by Maximum CTCAE Grade (PF-05082566-related)
timeFrame: Baseline up to 90 days after the last dose of study drug, approximately 27 months
measure: Number of Participants With Serious Adverse Events (SAEs) and Treatment Emergent Adverse Events (TEAEs) by Maximum CTCAE Grade (MK-3475-related)
timeFrame: Baseline up to 90 days after the last dose of study drug, approximately 27 months
measure: Number of Participants With Serious Adverse Events (SAEs) and Treatment Emergent Adverse Events (TEAEs) by Maximum CTCAE Grade (Both-related)
timeFrame: Baseline up to 90 days after the last dose of study drug, approximately 27 months
measure: Number of Participants With Laboratory Test Values Meeting Categorical Summarization Criteria by Maximum CTCAE Grade (Hematology)
timeFrame: Baseline up to 28 days after the last dose of study drug, approximately 25 months
measure: Number of Participants With Laboratory Test Values Meeting Categorical Summarization Criteria by Maximum CTCAE Grade (Chemistries)
timeFrame: Baseline up to 28 days after the last dose of study drug, approximately 25 months
measure: Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Criteria of Potential Clinical Concern
timeFrame: Baseline up to 28 days after the last dose of study drug, approximately 25 months
measure: Number of Participants With Shift From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status to Worst on Study
timeFrame: Baseline up to 28 days after the last dose of study drug, approximately 25 months
measure: Maximum Observed Serum Concentration (Cmax) of PF-05082566
timeFrame: During Cycle 5 on Day 1 at pre-dose, end of infusion, and at 2, 6, and 24 hours after the start of infusion, day 8 (168 hours) and day 15 (336 hours) after start of infusion
measure: Maximum Observed Serum Concentration (Cmax) of MK-3475
timeFrame: During Cycle 5 Day 1 at pre-dose; and end of infusion.
measure: Time for Cmax (Tmax) of PF-05082566
timeFrame: During Cycle 5 on Day 1 at pre-dose, end of infusion, and at 2, 6, and 24 hours after the start of infusion, day 8 (168 hours) and day 15 (336 hours) after start of infusion.
measure: Pre-dose Concentration During Multiple Dosing (Ctrough) of PF-05082566
timeFrame: During Cycle 5 on Day 1 at pre-dose, end of infusion, and at 2, 6, and 24 hours after the start of infusion, day 8 (168 hours) and day 15 (336 hours) after start of infusion.
measure: Pre-dose Concentration During Multiple Dosing (Ctrough) of MK-3475
timeFrame: During Cycle 5 Day 1 at pre-dose; and end of infusion.
measure: Terminal Half-life （t½）of PF-05082566
timeFrame: During Cycle 5 on Day 1 at pre-dose, end of infusion, and at 2, 6, and 24 hours after the start of infusion, day 8 (168 hours) and day 15 (336 hours) after start of infusion.
measure: Clearance (CL) of Study Drug of PF-05082566
timeFrame: During Cycle 5 on Day 1 at pre-dose, end of infusion, and at 2, 6, and 24 hours after the start of infusion, day 8 (168 hours) and day 15 (336 hours) after start of infusion.
measure: Volume of Distribution at Steady State (Vss) of PF-05082566
timeFrame: During Cycle 5 on Day 1 at pre-dose, end of infusion, and at 2, 6, and 24 hours after the start of infusion, day 8 (168 hours) and day 15 (336 hours) after start of infusion.
measure: Area Under the Serum Concentration-time Curve From Time 0 to Time Tau, the Dosing Interval, Where Tau = 504 Hours (21 Days) [AUCtau] for PF-05082566
timeFrame: During Cycle 5 on Day 1 at pre-dose, end of infusion, and at 2, 6, and 24 hours after the start of infusion, day 8 (168 hours) and day 15 (336 hours) after start of infusion.
measure: Number of Participants With Positive Anti-Drug Antibody (ADA) of PF-05082566
timeFrame: Pre-dose (Day 1), Cycles 1, 3, 5, 7, and subsequently pre-dose (Day 1) every 2 cycles up to Cycle 12, and every 4 cycles thereafter
measure: Number of Participants With Positive Anti-Drug Antibody (ADA) of MK-3475
timeFrame: Pre-dose in Cycles 1, 3, 5, 7 and subsequently pre dose every 2 cycles up to Cycle 12 and every 4 cycles thereafter and 28 days, and during follow-up (3 months and 6 months after the end of MK-3475 treatment).
measure: Number of Participants With Objective Tumor Response
timeFrame: Baseline, at Week 9, and then every 6 weeks up to 90 days after the last dose of study drug, approximately 27 months. For those patients who achieved a confirmed PR or CR, tumor assessments could be conducted as clinically indicated.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Administration Office
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center, Drug Information Center
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology-Oncology Clinic
state: California
city: Los Angeles
country: United States
facility: UCLA Oncology Center
state: California
city: New Haven
country: United States
facility: Smilow Cancer Center at Yale-New Haven Hospital
state: Connecticut
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale-New Haven
state: Connecticut
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: