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

Ovarian Cancer Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04152018
• Other study ID #: C3891001
• Secondary ID: 2020-004009-29
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: November 13, 2019
• Est. completion date: August 30, 2024

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 85
• Est. completion date: August 30, 2024
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Southern Medical Day Care Centre	Wollongong	New South Wales
Korea, Republic of	Asan Medical Center	Seoul	Seoul-teukbyeolsi [seoul]
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Slovakia	Narodny ustav srdcovych a cievnych chorob, a.s.	Bratislava
Slovakia	Onkologicky ustav sv. Alzbety, s.r.o.	Bratislava
Slovakia	Univerzitna nemocnica Bratislava	Bratislava
Slovakia	MR Poprad s.r.o.	Komárno
Slovakia	KARDIO, s.r.o.	Poprad
Slovakia	MR Poprad s.r.o.	Poprad
Slovakia	Nemocnica Poprad a.s.	Poprad
Slovakia	Nemocnica Poprad a.s.	Poprad
Slovakia	POKO Poprad, s.r.o., Ambulancia klinickej onkologie	Poprad
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United States	Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	University of Maryland Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	Siteman Cancer Center - West County	Creve Coeur	Missouri
United States	Duke Univ. Medical Center/Duke Cancer Center	Durham	North Carolina
United States	Investigational Chemotherapy Service	Durham	North Carolina
United States	Siteman Cancer Center - North County	Florissant	Missouri
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Monter Cancer Center	Lake Success	New York
United States	R.J. Zuckerberg Cancer Center	Lake Success	New York
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	UCLA Hematology Oncology	Los Angeles	California
United States	UCLA Hematology/Oncology	Los Angeles	California
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center - North County	Saint Louis	Missouri
United States	Siteman Cancer Center - South County	Saint Louis	Missouri
United States	Washington University School of Medicine Siteman Cancer Center	Saint Louis	Missouri
United States	Siteman Cancer Center - St. Peters	Saint Peters	Missouri
United States	NEXT Oncology	San Antonio	Texas
United States	UCLA Hematology/Oncology	Santa Monica	California
United States	HonorHealth Research Institute	Scottsdale	Arizona
United States	HonorHealth Scottsdale Shea Medical Center	Scottsdale	Arizona
United States	Scottsdale Healthcare Hospitals DBA HonorHealth	Scottsdale	Arizona
United States	Virginia G. Piper Cancer Pharmacy	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Korea, Republic of,  Slovakia,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Dose-limiting toxicities (DLT) for Dose Escalation and Dose Finding		Baseline up to 28 Days (Cycle 1)
Primary	Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities		Baseline up to approximately 24 months
Primary	Number of Participants With Adverse Events (AEs) According to Severity		Baseline up to approximately 24 months
Primary	Number of Participants With Adverse Events (AEs) According to Seriousness		Baseline up to up to approximately 24 months
Primary	Number of Participants With Adverse Events (AEs) by Relationship		Baseline up to approximately 24 months
Primary	Progression-Free Survival (PFS) for Dose Expansion	The period from study entry until disease progression, death or date of last contact.	Baseline up to 24 Months
Primary	Objective Response Rate - Percentage of Participants With Objective Response in Dose Expansion		Baseline up to 24 months
Primary	Duration of Response (DR) for Dose Expansion		Baseline up to 24 Months
Secondary	PF-06940434 after multiple doses PK parameters (Cmax).	Maximum observed plasma concentration of PF-06940434.	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).
Secondary	Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434.	Time zero extrapolated to the last quantifiable time point prior to the next dose.	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).
Secondary	Systemic Clearance (CL)	CL is a quantitative measure of the rate at which a drug substance is removed from the body.	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).
Secondary	Volume of Distribution (Vd)		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).
Secondary	Incidence and titers of anti-drug antibodies (ADA) against PF-06940434.		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).
Secondary	Incidence and titers of neutralizing antibodies (NAb) against PF-06940434.	Titers of neutralizing antibodies (NAb) against PF-06940434.	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).
Secondary	PK parameters of PF-06940434 and PF-06801591 (Cmax).	Maximum observed plasma concentration after multiple doses of PF-06940434 and PD-1 (PF-06801591).	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)
Secondary	Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434 and PF-06801591.	Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434 and PF-06801591.	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)
Secondary	Characterize the multiple dose PK of PF-06940434 following intravenous administration in combination with PF-06801591.	Maximum observed plasma concentration of PF-06940434.	Cycle 4 Day 1 (each cycle is 28 days)
Secondary	Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434.	Time zero extrapolated to the last quantifiable time point prior to the next dose.	Cycle 4 Day 1 (each cycle is 28 days)
Secondary	Number of participants with increased T-cells after PF-06940434 treatment.		Pre-dose on Day 1 of Cycle 1; pre-dose on Day 1 of Cycles 2 and 3 (each cycle is 28 days)
Secondary	Progression-Free Survival (PFS) for Dose Expansion	The period from study entry until disease progression, death or date of last contact.	Baseline to measured progression (up to approximately 24 months)
Secondary	Duration of Response (DR)		Baseline up to approximately 24 Months
Secondary	Number of Participants With Objective Response for Dose Expansion portion		Baseline up to 24 months
Secondary	Disease Control Rate (DCR)	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.	Every 8 weeks from the time of enrollment up to 2 years
Secondary	Trough concentrations of PF-06940434 and PF-06801591 in Dose Expansion		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)
Secondary	Plasma Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	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]
Secondary	Incidence and titers of anti-drug antibodies (ADA) against PF-06801591 in Dose Finding and Dose Expansion	Incidence and titers of anti-drug antibodies (ADA) against PF-06801591.	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].
Secondary	Incidence and titers of neutralizing antibodies (NAb) against PF-06801591 in Dose Finding and Dose Expansion.	Incidence and titers of neutralizing antibodies (NAb) against PF-06801591.	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].
Secondary	Overall Survival	The period from study entry until death or date of last contact (24 months)	From baseline to up to 2 years after last dose of study drug

External Links

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