The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

NCT04152018

Geo Regions

Clinical Study Trial ID
NCT04152018
Brief Title
Study of PF-06940434 in Patients With Advanced or Metastatic Solid Tumors.
Study Start Date
Study End Date
Enrollment Count
85
Conditions (Long)
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
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

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. Part 2:

  • Arm A SCCHN: * Primary tumor location of the oral cavity, oropharynx, hypopharynx or larynx. * PDL-1 expression positive and CPS ≥1. No prior systemic therapy administered in the recurrent or metastatic setting (except for systemic therapy given as part of a multimodal treatment for locally advanced disease).
  • Arm B RCC (clear cell):
    • 1 or 2 prior lines of therapy including PD-L1/PD-1 immunotherapy in combination or sequentially with antiangiogenic directed treatme
  • 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.
  • Active or prior autoimmune disease
  • Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) Hepatitis B, Hepatitis C, and known Human Immunodeficiency Virus infection or Acquired Immunodeficiency Syndrome-related illness
Study Design
Participant Group/Arm

EXPERIMENTAL: Dose Escalation

Single Agent Dose Escalation

Intervention/Treatment

DRUG: PF-06940434

PF-06940434 is given intravenously (IV) every 2 or 4 weeks in a 28 day cycle or every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated

Participant Group/Arm

EXPERIMENTAL: Dose Finding Anti-PD-1 Combination 1

Part 1B PF-06940434 plus anti-PD-1

Intervention/Treatment

DRUG: PF-06940434

PF-06940434 is given intravenously (IV) every 2 or 4 weeks in a 28 day cycle or every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated

DRUG: PF-06801591

PF-06801591 will be administered subcutaneously on Day 1 of each 28 day cycle or Day 1 of each 21 day cycle.

Participant Group/Arm

EXPERIMENTAL: Dose Expansion Arm A

PF-06940434 with anti-PD-1 in SCCHN

Intervention/Treatment

DRUG: PF-06940434

PF-06940434 is given intravenously (IV) every 2 or 4 weeks in a 28 day cycle or every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated

DRUG: PF-06801591

PF-06801591 will be administered subcutaneously on Day 1 of each 28 day cycle or Day 1 of each 21 day cycle.

Participant Group/Arm

EXPERIMENTAL: Dose Expansion Arm B

PF-06940434 with anti-PD-1 in RCC

Intervention/Treatment

DRUG: PF-06940434

PF-06940434 is given intravenously (IV) every 2 or 4 weeks in a 28 day cycle or every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated

DRUG: PF-06801591

PF-06801591 will be administered subcutaneously on Day 1 of each 28 day cycle or Day 1 of each 21 day cycle.

Participant Group/Arm

EXPERIMENTAL: Dose Expansion, Arm C

PF-06940434 with anti-PD-1 (both Q3W)

Intervention/Treatment

DRUG: PF-06940434

PF-06940434 is given intravenously (IV) every 2 or 4 weeks in a 28 day cycle or every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated

DRUG: PF-06801591

PF-06801591 will be administered subcutaneously on Day 1 of each 28 day cycle or Day 1 of each 21 day cycle.

Primary Outcome Measures
Outcome Measure

Number of participants with Dose-limiting toxicities (DLT) for Dose Escalation and Dose Finding

Time Frame

Baseline up to 28 Days (Cycle 1)

Outcome Measure

Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities

Time Frame

Baseline up to approximately 24 months

Outcome Measure

Number of Participants With Adverse Events (AEs) According to Severity

Time Frame

Baseline up to approximately 24 months

Outcome Measure

Number of Participants With Adverse Events (AEs) According to Seriousness

Time Frame

Baseline up to up to approximately 24 months

Outcome Measure

Number of Participants With Adverse Events (AEs) by Relationship

Time Frame

Baseline up to approximately 24 months

Outcome Measure

Progression-Free Survival (PFS) for Dose Expansion

Measure Description

The period from study entry until disease progression, death or date of last contact.

Time Frame

Baseline up to 24 Months

Outcome Measure

Objective Response Rate - Percentage of Participants With Objective Response in Dose Expansion

Time Frame

Baseline up to 24 months

Outcome Measure

Duration of Response (DR) for Dose Expansion

Time Frame

Baseline up to 24 Months

Secondary Outcome Measures
Outcome Measure

PF-06940434 after multiple doses PK parameters (Cmax).

Measure Description

Maximum observed plasma concentration 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).

Outcome Measure

Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434.

Measure Description

Time zero extrapolated to the last quantifiable time point prior to the next dose.

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).

Outcome Measure

Systemic Clearance (CL)

Measure Description

CL is a quantitative measure of the rate at which a drug substance is removed from the body.

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).

Outcome 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).

Outcome 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).

Outcome Measure

Incidence and titers of neutralizing antibodies (NAb) against PF-06940434.

Measure Description

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).

Outcome Measure

PK parameters of PF-06940434 and PF-06801591 (Cmax).

Measure Description

Maximum observed plasma concentration after multiple doses of PF-06940434 and PD-1 (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)

Outcome Measure

Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434 and PF-06801591.

Measure Description

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)

Outcome Measure

Characterize the multiple dose PK of PF-06940434 following intravenous administration in combination with PF-06801591.

Measure Description

Maximum observed plasma concentration of PF-06940434.

Time Frame

Cycle 4 Day 1 (each cycle is 28 days)

Outcome Measure

Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434.

Measure Description

Time zero extrapolated to the last quantifiable time point prior to the next dose.

Time Frame

Cycle 4 Day 1 (each cycle is 28 days)

Outcome 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)

Outcome Measure

Progression-Free Survival (PFS) for Dose Expansion

Measure Description

The period from study entry until disease progression, death or date of last contact.

Time Frame

Baseline to measured progression (up to approximately 24 months)

Outcome Measure

Duration of Response (DR)

Time Frame

Baseline up to approximately 24 Months

Outcome Measure

Number of Participants With Objective Response for Dose Expansion portion

Time Frame

Baseline up to 24 months

Outcome Measure

Disease Control Rate (DCR)

Measure 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.

Time Frame

Every 8 weeks from the time of enrollment up to 2 years

Outcome 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). For Part 2 Cohort 3, Day 1 of Every Cycle (each cycle is 21 days)

Outcome Measure

Plasma Decay Half-Life (t1/2)

Measure Description

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

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]

Outcome Measure

Incidence and titers of anti-drug antibodies (ADA) against PF-06801591 in Dose Finding and Dose Expansion

Measure Description

Incidence and titers of anti-drug antibodies (ADA) against PF-06801591.

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].

Outcome Measure

Incidence and titers of neutralizing antibodies (NAb) against PF-06801591 in Dose Finding and Dose Expansion.

Measure Description

Incidence and titers of neutralizing antibodies (NAb) against PF-06801591.

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].

Outcome Measure

Overall Survival

Measure Description

The period from study entry until death or date of last contact (24 months)

Time Frame

From baseline to up to 2 years after last dose of study drug

Sponsor
Pfizer
Data Updated date
Enrollment Status
Phases
Location
United States, Australia, Korea, Republic of, Slovakia, Taiwan
Study Type
Interventional