Study of PF-06940434 in Patients With Advanced or Metastatic Solid Tumors.
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| ClinicalTrials.gov Identifier: NCT04152018 |
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Recruitment Status :
Recruiting
First Posted : November 5, 2019
Last Update Posted : March 17, 2023
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Sponsor:
Pfizer
Information provided by (Responsible Party):
Pfizer
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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 2 cohorts at doses determined from Part 1B in order to further evaluate the safety of PF-06940434 in combination with anti-PD-1.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | Drug: PF-06940434 Drug: PF-06801591 | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 104 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | November 13, 2019 |
| Estimated Primary Completion Date : | February 12, 2025 |
| Estimated Study Completion Date : | February 12, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Melanoma
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dose Escalation
Single Agent Dose Escalation
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Drug: PF-06940434
PF-06940434 is given intravenously (IV) every 2 weeks in a 28 day cycle. Multiple dose levels will be evaluated |
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Experimental: Dose Finding Anti-PD-1 Combination 1
Part 1B PF-06940434 plus anti-PD-1
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Drug: PF-06940434
PF-06940434 is given intravenously (IV) every 2 weeks in a 28 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.
Other Name: Anti-PD-1 |
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Experimental: Dose Expansion Arm A
PF-06940434 with anti-PD-1 in SCCHN
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Drug: PF-06940434
PF-06940434 is given intravenously (IV) every 2 weeks in a 28 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.
Other Name: Anti-PD-1 |
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Experimental: Dose Expansion Arm B
PF-06940434 with anti-PD-1 in RCC
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Drug: PF-06940434
PF-06940434 is given intravenously (IV) every 2 weeks in a 28 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.
Other Name: Anti-PD-1 |
Primary Outcome Measures :
- Number of participants with Dose-limiting toxicities (DLT) for Dose Escalation and Dose Finding [ Time Frame: Baseline up to 28 Days (Cycle 1) ]
- Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities [ Time Frame: Baseline up to approximately 24 months ]
- Number of Participants With Adverse Events (AEs) According to Severity [ Time Frame: Baseline up to approximately 24 months ]
- Number of Participants With Adverse Events (AEs) According to Seriousness [ Time Frame: Baseline up to up to approximately 24 months ]
- Number of Participants With Adverse Events (AEs) by Relationship [ Time Frame: Baseline up to approximately 24 months ]
- Progression-Free Survival (PFS) for Dose Expansion [ Time Frame: Baseline up to 24 Months ]The period from study entry until disease progression, death or date of last contact.
- Objective Response Rate - Percentage of Participants With Objective Response in Dose Expansion [ Time Frame: Baseline up to 24 months ]
- Duration of Response (DR) for Dose Expansion [ Time Frame: Baseline up to 24 Months ]
Secondary Outcome Measures :
- 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) ]Maximum observed plasma concentration of PF-06940434.
- 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) ]Time zero extrapolated to the last quantifiable time point prior to the next dose.
- 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) ]CL is a quantitative measure of the rate at which a drug substance is removed from the body.
- 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) ]
- 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) ]
- 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) ]Titers of neutralizing antibodies (NAb) against PF-06940434.
- 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) ]Maximum observed plasma concentration after multiple doses of PF-06940434 and PD-1 (PF-06801591).
- 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) ]Area under the curve from time zero extrapolated to the last quantifiable dose of PF-06940434 and PF-06801591.
- 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) ]Maximum observed plasma concentration of PF-06940434.
- 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) ]Time zero extrapolated to the last quantifiable time point prior to the next dose.
- 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) ]
- Progression-Free Survival (PFS) for Dose Expansion [ Time Frame: Baseline to measured progression (up to approximately 24 months) ]The period from study entry until disease progression, death or date of last contact.
- Duration of Response (DR) [ Time Frame: Baseline up to approximately 24 Months ]
- Number of Participants With Objective Response for Dose Expansion portion [ Time Frame: Baseline up to 24 months ]
- Disease Control Rate (DCR) [ Time Frame: Every 8 weeks from the time of enrollment up to 2 years ]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.
- 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) ]
- 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] ]Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
- 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] ]Incidence and titers of anti-drug antibodies (ADA) against PF-06801591.
- 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] ]Incidence and titers of neutralizing antibodies (NAb) against PF-06801591.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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:
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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).
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04152018
Contacts
| Contact: Pfizer CT.gov Call Center | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
Locations
Show 33 study locations
Sponsors and Collaborators
Pfizer
Investigators
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
Additional Information:
| Responsible Party: | Pfizer |
| ClinicalTrials.gov Identifier: | NCT04152018 |
| Other Study ID Numbers: |
C3891001 2020-004009-29 ( EudraCT Number ) |
| First Posted: | November 5, 2019 Key Record Dates |
| Last Update Posted: | March 17, 2023 |
| Last Verified: | March 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Plan Description: | Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Carcinoma Carcinoma, Squamous Cell Endometrial Neoplasms Squamous Cell Carcinoma of Head and Neck Bile Duct Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Squamous Cell Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Genital Diseases, Female |
Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Genital Neoplasms, Female Urogenital Neoplasms Genital Diseases Head and Neck Neoplasms Uterine Neoplasms Uterine Diseases Biliary Tract Neoplasms Bile Duct Diseases Biliary Tract Diseases |