Clinical trial NCT04152018: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2019-11-05
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Open-label, multi-center, non-randomized, multiple dose, safety, tolerability, pharmacokinetic, and pharmacodynamics and clinical activity study of PF-06940434 (Integrin alpha-V/beta-8 Antagonist) 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) and dose expansion (Part 2). Part 2 Dose Combination Expansion will enroll participants into 3 cohorts at doses determined from Part 1B in order to further evaluate the safety of PF-06940434 in combination with anti-PD-1.


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.

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 treatment
* 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

Primary outcomes:
measure: Number of participants with Dose-limiting toxicities (DLT) for Dose Escalation and Dose Finding
timeFrame: Baseline up to 28 Days (Cycle 1)
measure: Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities
timeFrame: Baseline up to approximately 24 months
measure: Number of Participants With Adverse Events (AEs) According to Severity
timeFrame: Baseline up to approximately 24 months
measure: Number of Participants With Adverse Events (AEs) According to Seriousness
timeFrame: Baseline up to up to approximately 24 months
measure: Number of Participants With Adverse Events (AEs) by Relationship
timeFrame: Baseline up to approximately 24 months
measure: Progression-Free Survival (PFS) for Dose Expansion
timeFrame: Baseline up to 24 Months
measure: Objective Response Rate - Percentage of Participants With Objective Response in Dose Expansion
timeFrame: Baseline up to 24 months
measure: Duration of Response (DR) for Dose Expansion
timeFrame: Baseline up to 24 Months
Secondary outcomes:
measure: PF-06940434 after multiple doses PK parameters (Cmax).
timeFrame: 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).
measure: Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434.
timeFrame: 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).
measure: Systemic Clearance (CL)
timeFrame: 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).
measure: Volume of Distribution (Vd)
timeFrame: 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).
measure: Incidence and titers of anti-drug antibodies (ADA) against PF-06940434.
timeFrame: 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).
measure: Incidence and titers of neutralizing antibodies (NAb) against PF-06940434.
timeFrame: 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).
measure: PK parameters of PF-06940434 and PF-06801591 (Cmax).
timeFrame: 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)
measure: Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434 and PF-06801591.
timeFrame: 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)
measure: Characterize the multiple dose PK of PF-06940434 following intravenous administration in combination with PF-06801591.
timeFrame: Cycle 4 Day 1 (each cycle is 28 days)
measure: Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434.
timeFrame: Cycle 4 Day 1 (each cycle is 28 days)
measure: Number of participants with increased T-cells after PF-06940434 treatment.
timeFrame: Pre-dose on Day 1 of Cycle 1; pre-dose on Day 1 of Cycles 2 and 3 (each cycle is 28 days)
measure: Progression-Free Survival (PFS) for Dose Expansion
timeFrame: Baseline to measured progression (up to approximately 24 months)
measure: Duration of Response (DR)
timeFrame: Baseline up to approximately 24 Months
measure: Number of Participants With Objective Response for Dose Expansion portion
timeFrame: Baseline up to 24 months
measure: Disease Control Rate (DCR)
timeFrame: Every 8 weeks from the time of enrollment up to 2 years
measure: Trough concentrations of PF-06940434 and PF-06801591 in Dose Expansion
timeFrame: 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)
measure: Plasma Decay Half-Life (t1/2)
timeFrame: 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]
measure: Incidence and titers of anti-drug antibodies (ADA) against PF-06801591 in Dose Finding and Dose Expansion
timeFrame: 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].
measure: Incidence and titers of neutralizing antibodies (NAb) against PF-06801591 in Dose Finding and Dose Expansion.
timeFrame: 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].
measure: Overall Survival
timeFrame: From baseline to up to 2 years after last dose of study drug
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Scottsdale Shea Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology Oncology
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Baltimore
country: United States
facility: Greenebaum Comprehensive Cancer Center
state: Maryland
city: Creve Coeur
country: United States
facility: Siteman Cancer Center - West County
state: Missouri
city: Florissant
country: United States
facility: Siteman Cancer Center - North County
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine Siteman Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - South County
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center - St. Peters
state: Missouri
city: Durham
country: United States
facility: Duke Univ. Medical Center/Duke Cancer Center
state: North Carolina
city: Durham
country: United States
facility: Investigational Chemotherapy Service
state: North Carolina
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre
state: New South Wales
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul-teukbyeolsi [seoul]
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Bratislava
country: Slovakia
facility: Onkologicky ustav sv. Alzbety, s.r.o.
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava
city: Bratislava
country: Slovakia
facility: Narodny ustav srdcovych a cievnych chorob, a.s.
city: Komárno
country: Slovakia
facility: MR Poprad s.r.o.
city: Poprad
country: Slovakia
facility: KARDIO, s.r.o.
city: Poprad
country: Slovakia
facility: POKO Poprad, s.r.o., Ambulancia klinickej onkologie
city: Poprad
country: Slovakia
facility: Nemocnica Poprad a.s.
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: