Clinical Trials /

Study of PF‑06940434 in Patients With Advanced or Metastatic Solid Tumors.

NCT04152018

Description:

Open-label, multi-center, non-randomized, multiple dose, safety, tolerability, pharmacokinetic, and pharmacodynamics and clinical activity study of PF-06940434 in patients with SCCHN (Squamous Cell Carcinoma of the Head and Neck), renal cell carcinoma (RCC - clear cell and papillary), ovarian, gastric, esophageal, esophageal (adeno and squamous), lung squamous cell, pancreatic and biliary duct, endometrial, melanoma and urothelial tumors. This study contains two parts, single agent dose escalation (Part 1A), dose finding of PF 06940434 in combination with anti-PD-1 (Part 1B), biopsy cohorts with monotherapy lead-in at the maximum tolerated dose (MTD) or maximum administered dose (MAD), followed by combination of anti-PD-1 [PF-06801591] (Part 1C) followed by dose expansion (Part 2). Part 2 Dose Combination Expansion will enroll participants into 2 cohorts at doses determined from Part 1B in order to further evaluate the safety of PF-06940434 in combination with anti-PD-1.

Related Conditions:
  • Biliary Tract Carcinoma
  • Clear Cell Renal Cell Carcinoma
  • Endometrial Carcinoma
  • Esophageal Adenocarcinoma
  • Esophageal Squamous Cell Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Melanoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Papillary Renal Cell Carcinoma
  • Renal Cell Carcinoma
  • Squamous Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of PF‑06940434 in Patients With Advanced or Metastatic Solid Tumors.
  • Official Title: A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF ESCALATING DOSES OF PF-06940434 IN PATIENTS WITH ADVANCED OR METASTATIC SOLID TUMORS

Clinical Trial IDs

  • ORG STUDY ID: C3891001
  • NCT ID: NCT04152018

Conditions

  • Squamous Cell Carcinoma of the Head and Neck
  • Renal Cell Carcinoma
  • Ovarian Cancer
  • Gastric Cancer
  • Esophageal Cancer
  • Lung Squamous Cell Carcinoma
  • Pancreatic Cancer
  • Bile Duct Cancer
  • Endometrial Cancer
  • Melanoma Cancer
  • Urothelial Cancer

Interventions

DrugSynonymsArms
PF-06940434Dose Escalation
PF-06801591Anti-PD-1Dose Finding Anti-PD-1 Combination 1

Purpose

Open-label, multi-center, non-randomized, multiple dose, safety, tolerability, pharmacokinetic, and pharmacodynamics and clinical activity study of PF-06940434 in patients with SCCHN (Squamous Cell Carcinoma of the Head and Neck), renal cell carcinoma (RCC - clear cell and papillary), ovarian, gastric, esophageal, esophageal (adeno and squamous), lung squamous cell, pancreatic and biliary duct, endometrial, melanoma and urothelial tumors. This study contains two parts, single agent dose escalation (Part 1A), dose finding of PF 06940434 in combination with anti-PD-1 (Part 1B), biopsy cohorts with monotherapy lead-in at the maximum tolerated dose (MTD) or maximum administered dose (MAD), followed by combination of anti-PD-1 [PF-06801591] (Part 1C) followed by dose expansion (Part 2). Part 2 Dose Combination Expansion will enroll participants into 2 cohorts at doses determined from Part 1B in order to further evaluate the safety of PF-06940434 in combination with anti-PD-1.

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalSingle Agent Dose Escalation
  • PF-06940434
Dose Finding Anti-PD-1 Combination 1ExperimentalPart 1B PF-06940434 plus anti-PD-1
  • PF-06940434
  • PF-06801591
Dose Finding Anti-PD-1 Combination 2ExperimentalPart 1C PF-06940434 plus anti-PD-1
  • PF-06940434
  • PF-06801591
Dose Expansion Arm AExperimentalPF-06940434 with anti-PD-1 in SCCHN
  • PF-06940434
  • PF-06801591
Dose Expansion Arm BExperimentalPF-06940434 with anti-PD-1 in RCC
  • PF-06940434
  • PF-06801591

Eligibility Criteria

        Inclusion Criteria:

          -  Histological or cytological diagnosis of SCCHN, RCC (clear cell and papillary cell),
             ovarian, gastric, esophageal (adeno and squamous), lung squamous cell, pancreatic and
             biliary duct, endometrial, melanoma, or urothelial cancer.

          -  Adequate bone marrow, kidney and liver function.

          -  Performance status of 0 or 1.

        Exclusion Criteria:

          -  Participant disease status is suitable for local therapy administered with curative
             intent.

          -  Hypertension that cannot be controlled by medications.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with Dose-limiting toxicities (DLT) for Dose Escalation and Dose Finding
Time Frame:Baseline up to 28 Days (Cycle 1)
Safety Issue:
Description:The period from study entry until disease progression, death or date of last contact.

Secondary Outcome Measures

Measure:PF-06940434 after multiple doses PK parameters (Cmax).
Time Frame:Pre-dose on Cycle 1 Day 1 and on days 3, 8, and 15 of Cycle 1; Day 1 and Day 15 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days)
Safety Issue:
Description:Maximum observed plasma concentration of PF-06940434.
Measure:Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434.
Time Frame:Pre-dose on Cycle 1 Day 1 and on days 3, 8, and 15 of Cycle 1; Day 1 and Day 15 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days)
Safety Issue:
Description:Time zero extrapolated to the last quantifiable time point prior to the next dose.
Measure:Systemic Clearance (CL)
Time Frame:Pre-dose on Cycle 1 Day 1 and on days 3, 8, and 15 of Cycle 1; Day 1 and Day 15 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days)
Safety Issue:
Description:CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Measure:Volume of Distribution (Vd)
Time Frame:Pre-dose on Cycle 1 Day 1 and on days 3, 8, and 15 of Cycle 1; Day 1 and Day 15 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days)
Safety Issue:
Description:
Measure:Incidence and titers of anti-drug antibodies (ADA) against PF-06940434.
Time Frame:Pre-dose on Days 1 and 15 of Cycle 1, pre-dose on Day 1 of Cycles 2 and 3, pre-dose on Day 1 of Cycle 4, pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days)
Safety Issue:
Description:
Measure:Incidence and titers of neutralizing antibodies (NAb) against PF-06940434.
Time Frame:Pre-dose on Days 1 and 15 of Cycle 1, pre-dose on Day 1 of Cycles 2 and 3, pre-dose on Day 1 of Cycle 4, pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days)
Safety Issue:
Description:Titers of neutralizing antibodies (NAb) against PF-06940434.
Measure:PK parameters of PF-06940434 and PF-06801591 (Cmax).
Time Frame:Pre-dose on Cycle 1 Day 1 and on day 15 of Cycle 1; Day 1 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days)
Safety Issue:
Description:Maximum observed plasma concentration after multiple doses of PF-06940434 and PD-1 (PF-06801591).
Measure:Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434 and PF-06801591.
Time Frame:Pre-dose on Cycle 1 Day 1 and on day 15 of Cycle 1; Day 1 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (each cycle is 28 days)
Safety Issue:
Description:Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434 and PF-06801591.
Measure:Characterize the multiple dose PK of PF-06940434 following intravenous administration in combination with PF-06801591.
Time Frame:Cycle 4 Day 1 (each cycle is 28 days)
Safety Issue:
Description:Maximum observed plasma concentration of PF-06940434.
Measure:Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434.
Time Frame:Cycle 4 Day 1 (each cycle is 28 days)
Safety Issue:
Description:Time zero extrapolated to the last quantifiable time point prior to the next dose.
Measure:Number of participants with increased T-cells after PF-06940434 treatment.
Time Frame:Pre-dose on Day 1 of Cycle 1; pre-dose on Day 1 of Cycles 2 and 3 (each cycle is 28 days)
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS) for Dose Expansion
Time Frame:Baseline to measured progression (up to approximately 24 months)
Safety Issue:
Description:The period from study entry until disease progression, death or date of last contact.
Measure:Duration of Response (DR)
Time Frame:Baseline up to approximately 24 Months
Safety Issue:
Description:
Measure:Number of Participants With Objective Response for Dose Expansion portion
Time Frame:Baseline up to 24 months
Safety Issue:
Description:
Measure:Disease Control Rate (DCR)
Time Frame:Every 8 weeks from the time of enrollment up to 2 years
Safety Issue:
Description:DCR is defined as the percent of participants with a confirmed complete response (CR), partial response (PR) or stable disease (SD) according to RECIST 1.1.
Measure:Trough concentrations of PF-06940434 and PF-06801591 in Dose Expansion
Time Frame:Day 1 of Cycle 1 though 4, Day 1 of every 2 Cycles starting from Cycle 5 up to 24 months (each cycle is 28 days)
Safety Issue:
Description:
Measure:Plasma Decay Half-Life (t1/2)
Time Frame:Pre-dose on Cycle 1 Day 1 and on days 3, 8, and 15 of Cycle 1; Day 1 and Day 15 of Cycles 2 and 3; Days 1, 3, 8, and 15 of Cycle 4 and Pre-dose on Day 1 of every cycle thereafter and at end of treatment (up to 24 Months) [each cycle is 28 days]
Safety Issue:
Description:Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Measure:Incidence and titers of anti-drug antibodies (ADA) against PF-06801591 in Dose Finding and Dose Expansion
Time Frame:Pre-dose on Days 1 and 15 of Cycle 1, pre-dose on Day 1 of Cycles 2 and 3, pre-dose on Day 1 of Cycle 4, pre-dose on Day 1 of every cycle thereafter and at end of treatment (up to 24 Months) [each cycle is 28 days]
Safety Issue:
Description:Incidence and titers of anti-drug antibodies (ADA) against PF-06801591.
Measure:Incidence and titers of neutralizing antibodies (NAb) against PF-06801591 in Dose Finding and Dose Expansion.
Time Frame:Pre-dose on Days 1 and 15 of Cycle 1, pre-dose on Day 1 of Cycles 2 and 3, pre-dose on Day 1 of Cycle 4, pre-dose on Day 1 of every cycle thereafter and at end of treatment (up to 24 Months) [each cycle is 28 days]
Safety Issue:
Description:Incidence and titers of neutralizing antibodies (NAb) against PF-06801591.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pfizer

Last Updated

December 16, 2019