Clinical Trials /

PF-06801591 (PD-1 Inhibitor) in Participants With Advanced Malignancies

NCT04181788

Description:

This is a Phase 1b/2 protocol to evaluate pharmacokinetics, safety, efficacy, and pharmacodynamics of PF-06801591, a programmed death-1(PD-1) antagonist monoclonal antibody (mAb) in participants with advanced malignancies. This study consists of 2 parts: Phase 1b part in patients with advanced malignancies in Japan and a global Phase 2 part in non small cell lung cancer (NSCLC) patients.

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PF-06801591 (PD-1 Inhibitor) in Participants With Advanced Malignancies
  • Official Title: A Phase 1b/2 Open-Label Study to Evaluate Pharmacokinetics, Safety, Efficacy, and Pharmacodynamics of PF-06801591 (PD-1 Inhibitor) in Participants With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: B8011007
  • SECONDARY ID: 2019-003818-14
  • NCT ID: NCT04181788

Conditions

  • Advanced Malignancies
  • Non-small-cell Lung Cancer

Interventions

DrugSynonymsArms
PF-06801591Arm A1 (Phase 1b)

Purpose

This is a Phase 1b/2 protocol to evaluate pharmacokinetics, safety, efficacy, and pharmacodynamics of PF-06801591, a programmed death-1(PD-1) antagonist monoclonal antibody (mAb) in participants with advanced malignancies. This study consists of 2 parts: Phase 1b part in patients with advanced malignancies in Japan and a global Phase 2 part in non small cell lung cancer (NSCLC) patients.

Trial Arms

NameTypeDescriptionInterventions
Arm A1 (Phase 1b)Experimental
  • PF-06801591
Arm B1 (Phase 1b)Experimental
  • PF-06801591
Arm A2 (Phase 2)Experimental
  • PF-06801591
Arm B2 (Phase 2)Experimental
  • PF-06801591

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥18 years (≥ 20 years in Japan)

          -  Easter Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Adequate bone marrow function, renal and liver functions Phase 1b

          -  Histological or Cytological diagnosis of advanced solid tumor with clinical evidence
             of response to anti-PD-1 or PD-L1 agent

          -  Participant must have received at least 1 prior line of therapy for recurrent or
             metastatic disease, and must have progressed/relapsed, be refractory, or intolerant to
             standard therapy approved for the specific tumor type Phase 2

          -  Participants must have a documented diagnosis of stage III where participants are not
             candidates for surgical resection or definitive chemoradiation, or stage IV NSCLC

          -  EGFR mutation, BRAF mutation, and ALK or ROS1 translocation/rearrangement are not
             permitted

          -  Participants whose tumor is known to be PD-L1 positive (Tumor Proportion Score [TPS]
             ≥1%) or unknown are eligible

          -  Up to 1 line of prior therapy in advanced disease settings allowed

          -  Participant should not have received prior treatment with anti PD-1/PD-L1 drugs

          -  At least one measurable lesion as defined by RECIST version 1.1

        Exclusion Criteria:

          -  Participants with known symptomatic brain metastases requiring steroids

          -  Baseline (defined as the timepoint prior to the first dose of drug, i.e screening or
             Cycle 1 Day 1 (C1D1))12-lead electrocardiogram (ECG) that demonstrates clinically
             relevant abnormalities that may affect participant safety or interpretation of study
             results

          -  Hypertension that cannot be controlled by medications (eg, >150/90 mmHg) despite
             optimal medical therapy

          -  Known or suspected hypersensitivity to active ingredient or excipients of the study
             drug.

          -  History of Grade ≥3 immune mediated AE (including AST/ ALT elevations that where
             considered drug related and cytokine release syndrome [CRS]) that was considered
             related to prior immune modulatory therapy (eg, immune checkpoint inhibitors,
             co-stimulatory agents, etc.) and required immunosuppressive therapy (For Phase 1b
             only)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1b: Number of participants with Dose-Limiting Toxicities (DLT)
Time Frame:At the end of cycle 1 (28 days) for Arm A1 and (42 days) for Arm B1
Safety Issue:
Description:A DLT is any of a predefined set of unacceptable adverse events that are observed and that are related to the investigational agent.

Secondary Outcome Measures

Measure:Number of participants with Treatment-Emergent Adverse Events
Time Frame:Baseline and up to 90 days post treatment period
Safety Issue:
Description:Assessment of the overall safety and tolerability.
Measure:Number of participants with laboratory abnormalities
Time Frame:Baseline and up to 30 days post treatment period
Safety Issue:
Description:Assessment of the overall safety and tolerability.
Measure:Pharmacokinetic parameters: AUC after first dose
Time Frame:Arms A1/A2 (each cycle/28 days): Day 1, 8, 15, 22 of Cycles 1 and 4, Day 1 of Cycles 2, 3, 5, 6, 8, 10 and EOT (up to 24 months). Arms B1/B2 (each cycle/42 days): day 1, 8, 15, 29 of Cycles 1 and 3, Day 1 of Cycles 2, 4, 5, 7 and EOT (up to 24 months)
Safety Issue:
Description:AUC is defined as the area under the curve after the first dose.
Measure:Pharmacokinetic parameters: Ctrough after first dose
Time Frame:Arms A1/A2 (each cycle/28 days): Day 1, 8, 15, 22 of Cycles 1 and 4, Day 1 of Cycles 2, 3, 5, 6, 8, 10 and EOT (up to 24 months). Arms B1/B2 (each cycle/42 days): day 1, 8, 15, 29 of Cycles 1 and 3, Day 1 of Cycles 2, 4, 5, 7 and EOT (up to 24 months)
Safety Issue:
Description:Ctrough after first dose is defined as the concentration at the end of the first dosing interval of PF-06801591.
Measure:Pharmacokinetic parameters: Ctrough at steady State
Time Frame:Arms A1/A2 (each cycle/28 days): Day 1, 8, 15, 22 of Cycles 1 and 4, Day 1 of Cycles 2, 3, 5, 6, 8, 10 and EOT (up to 24 months). Arms B1/B2 (each cycle/42 days): day 1, 8, 15, 29 of Cycles 1 and 3, Day 1 of Cycles 2, 4, 5, 7 and EOT (up to 24 months)
Safety Issue:
Description:Ctrough at steady state is defined as the concentration at the end of PF-06801591 dosage interval at steady state.
Measure:Anti-Drug Antibody (ADA) levels of PF-06801591/Neutralizing antibodies titers for PF-06801591
Time Frame:Arm A1 and Arm A2 (each cycle is 28 days): On day 1 of cycles 1, 2, 3, 4, 6, 8, 10 and EOT (up to 24 months). Arm B1 and Arm B2 (each cycle is 42 days): On day 1 of cycles 1, 2, 3, 4, 5, 7 and EOT (up to 24 months)
Safety Issue:
Description:Immunogenicity assessment of PF-06801591.
Measure:Number of participants with Objective Response
Time Frame:Every 12 weeks (up to 24 months)
Safety Issue:
Description:Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 from the date of first dose of study treatment (Phase 1b) or randomization (Phase 2) until the date of the first documentation of progression of disease.
Measure:Time to Response (TTR)
Time Frame:Every 12 weeks (up to 24 months)
Safety Issue:
Description:TTR is the time from first dose of study treatment (Phase 1b) or randomization (Phase 2) to the date of first documentation of objective tumor response (CR or PR) by RECIST 1.1 that is subsequently confirmed.
Measure:PD-L1 expression in baseline
Time Frame:Baseline
Safety Issue:
Description:Correlation(s) between PD-L1 expression in baseline tumor tissue and pharmacodynamic markers and/or clinical activity.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • Advanced solid tumors
  • NSCLC

Last Updated

November 27, 2019