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

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ClinicalTrials.gov Identifier: NCT04152018
Recruitment Status : Not yet recruiting
First Posted : November 5, 2019
Last Update Posted : November 5, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
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.

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

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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
Estimated Study Start Date : November 7, 2019
Estimated Primary Completion Date : June 27, 2023
Estimated Study Completion Date : June 27, 2023


Arm Intervention/treatment
Experimental: Dose Escalation
Single Agent Dose Escalation
Drug: PF-06940434
PF-06940434 is given intravenously (IV) every 2 weeks in a 28 day cycle. Multiple dose levels will be evaluated

Experimental: Dose Finding Anti-PD-1 Combination 1
Part 1B PF-06940434 plus anti-PD-1
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

Experimental: Dose Finding Anti-PD-1 Combination 2
Part 1C PF-06940434 plus anti-PD-1
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

Experimental: Dose Expansion Arm A
PF-06940434 with anti-PD-1 in SCCHN
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

Experimental: Dose Expansion Arm B
PF-06940434 with anti-PD-1 in RCC
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 :
  1. Number of participants with Dose-limiting toxicities (DLT) for Dose Escalation and Dose Finding [ Time Frame: Baseline up to 28 Days (Cycle 1) ]
  2. Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities [ Time Frame: Baseline up to approximately 24 months ]
  3. Number of Participants With Adverse Events (AEs) According to Severity [ Time Frame: Baseline up to approximately 24 months ]
  4. Number of Participants With Adverse Events (AEs) According to Seriousness [ Time Frame: Baseline up to up to approximately 24 months ]
  5. Number of Participants With Adverse Events (AEs) by Relationship [ Time Frame: Baseline up to approximately 24 months ]
  6. 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.

  7. Objective Response Rate - Percentage of Participants With Objective Response in Dose Expansion [ Time Frame: Baseline up to 24 months ]
  8. Duration of Response (DR) for Dose Expansion [ Time Frame: Baseline up to 24 Months ]

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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) ]
  5. 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) ]
  6. 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.

  7. 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).

  8. 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.

  9. 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.

  10. 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.

  11. 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) ]
  12. 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.

  13. Duration of Response (DR) [ Time Frame: Baseline up to approximately 24 Months ]
  14. Number of Participants With Objective Response for Dose Expansion portion [ Time Frame: Baseline up to 24 months ]
  15. 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.

  16. 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) ]
  17. 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.

  18. 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.

  19. 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.



Information from the National Library of Medicine

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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.
  • 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.

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
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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United States, Texas
NEXT Oncology Not yet recruiting
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT04152018     History of Changes
Other Study ID Numbers: C3891001
First Posted: November 5, 2019    Key Record Dates
Last Update Posted: November 5, 2019
Last Verified: November 2019
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.

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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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Endometrial Neoplasms
Bile Duct Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Digestive System Neoplasms
Neoplasms by Site
Genital Neoplasms, Female
Urogenital Neoplasms
Head and Neck Neoplasms
Uterine Neoplasms
Biliary Tract Neoplasms
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Digestive System Diseases
Genital Diseases, Female
Uterine Diseases
Bile Duct Diseases
Biliary Tract Diseases