A Study Of 4-1BB Agonist PF-05082566 Plus PD-1 Inhibitor MK-3475 In Patients With Solid Tumors (B1641003/KEYNOTE-0036)

NCT02179918 | Completed Phase 1 Results

• 2 other identifiers: B1641003KEYNOTE-0036
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 9

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.

Conditions

Advanced Solid Tumors

Keywords

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose-Limiting Toxicities (DLT) of PF-05082566 in Combination With MK-3475

  Severity of adverse events (AEs) was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. For the purpose of dose escalation, any of the following AEs occurring during the DLT observation period that were attributable to one or both study drugs were classified as DLTs. 1) Hematologic: Grade 4 neutropenia; Febrile neutropenia, defined as absolute neutrophil count (ANC) \<1000/mm3 with a single temperature of \>38.3C(101F) or a sustained temperature of 38C (100.4F) for more than 1 hour; Grade\>=3 neutropenic infection; Grade\>=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia. 2) Non hematologic: Grade\>=3 toxicities (non-laboratory); Grade\>=3 nausea, vomiting or diarrhea despite maximal medical therapy; Grade 4 aspartate aminotransferase (AST) and alanine aminotransferase (ALT). 3) Other (non-AST/ALT) non-hematologic Grade\>=3 laboratory value. 4) Inability to complete 2 infusions of MK-3475 and PF-05082566 during the DLT observation period.

  First 2 cycles of treatment up to 24 months

Secondary Outcomes (20)

• Number of Subjects With Serious Adverse Events (SAEs) and Treatment Emergent Adverse Events (TEAEs) by Maximum CTCAE Grade (All Causalities)

  Baseline up to 90 days after the last dose of study drug, approximately 27 months

• Number of Participants With Serious Adverse Events (SAEs) and Treatment Emergent Adverse Events (TEAEs) by Maximum CTCAE Grade (PF-05082566-related)

  Baseline up to 90 days after the last dose of study drug, approximately 27 months

• Number of Participants With Serious Adverse Events (SAEs) and Treatment Emergent Adverse Events (TEAEs) by Maximum CTCAE Grade (MK-3475-related)

  Baseline up to 90 days after the last dose of study drug, approximately 27 months

• Number of Participants With Serious Adverse Events (SAEs) and Treatment Emergent Adverse Events (TEAEs) by Maximum CTCAE Grade (Both-related)

  Baseline up to 90 days after the last dose of study drug, approximately 27 months

• Number of Participants With Laboratory Test Values Meeting Categorical Summarization Criteria by Maximum CTCAE Grade (Hematology)

  Baseline up to 28 days after the last dose of study drug, approximately 25 months

Study Arms (1)

PF-05082566 +MK-3475

EXPERIMENTAL

PF-05082566 +MK-3475

Drug: PF-05082566; Drug: MK-3475

Interventions

PF-05082566 DRUG

Starting dose of 0.45 mg/kg q3wks IV, dose escalation

PF-05082566 +MK-3475

MK-3475 DRUG

2 mg/kg q3wks, IV

Also known as: pembrolizumab

PF-05082566 +MK-3475

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Pfizer: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (9)

Research Administration Office

Los Angeles, California, 90095, United States

Location

Ronald Reagan UCLA Medical Center, Drug Information Center

Los Angeles, California, 90095, United States

Location

UCLA Hematology-Oncology Clinic

Los Angeles, California, 90095, United States

Location

UCLA Oncology Center

Los Angeles, California, 90095, United States

Location

Smilow Cancer Center at Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, 06510, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

utomilumab; pembrolizumab

Limitations and Caveats

The study was terminated early due to strategic reasons before any expansion cohort patient was enrolled.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2014
• First Posted: July 2, 2014
• Study Start: August 1, 2014
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: February 8, 2019
• Results First Posted: October 11, 2018

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)