Clinical Trials /

Study to Test the Safety and Tolerability of PF-07209960 in Advanced or Metastatic Solid Tumors

NCT04628780

Description:

This is a first-in-human, Phase 1, open label, multicenter, multiple dose, dose escalation and dose expansion study intended to evaluate the safety, pharmacokinetic, pharmacodynamic, and potential clinical benefit of PF-07209960, an anti-PD-1 targeting IL-15 fusion protein, in participants with selected locally advanced or metastatic solid tumors for whom no standard therapy is available, or would not be an appropriate option in the opinion of the participant and their treating physician, or participants who have refused standard therapy. The study contains 2 parts, single agent Dose Escalation (Part 1) to determine the recommended dose of PF-07209960, followed by Dose Expansion (Part 2) in selected tumor types at the recommended dose.

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study to Test the Safety and Tolerability of PF-07209960 in Advanced or Metastatic Solid Tumors
  • Official Title: A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY TO EVALUATE SAFETY, TOLERABILITY, PHARMACOKINETIC, PHARMACODYNAMIC, AND ANTI-TUMOR ACTIVITY OF PF-07209960 IN PARTICIPANTS WITH ADVANCED OR METASTATIC SOLID TUMORS

Clinical Trial IDs

  • ORG STUDY ID: C4011001
  • NCT ID: NCT04628780

Conditions

  • Non-small-cell Lung Cancer
  • Squamous Cell Carcinoma of the Head and Neck
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
  • Colorectal Carcinoma
  • Ovarian Carcinoma

Interventions

DrugSynonymsArms
PF-07209960Dose Escalation (Part 1)

Purpose

This is a first-in-human, Phase 1, open label, multicenter, multiple dose, dose escalation and dose expansion study intended to evaluate the safety, pharmacokinetic, pharmacodynamic, and potential clinical benefit of PF-07209960, an anti-PD-1 targeting IL-15 fusion protein, in participants with selected locally advanced or metastatic solid tumors for whom no standard therapy is available, or would not be an appropriate option in the opinion of the participant and their treating physician, or participants who have refused standard therapy. The study contains 2 parts, single agent Dose Escalation (Part 1) to determine the recommended dose of PF-07209960, followed by Dose Expansion (Part 2) in selected tumor types at the recommended dose.

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation (Part 1)ExperimentalParticipants will receive PF-07209960 at escalating dose levels
  • PF-07209960
Dose Expansion (Part 2) - Cohort 1 (NSCLC)ExperimentalParticipants with non-small cell lung cancer (NSCLC) will receive PF-07209960 at the recommended dose from Part 1
  • PF-07209960
Dose Expansion (Part 2) - Cohort 2 (RCC)ExperimentalParticipants with renal cell carcinoma (RCC) will receive PF-07209960 at the recommended dose from Part 1
  • PF-07209960
Dose Expansion (Part 2) - Cohort 3 (UC)ExperimentalParticipants with urothelial carcinoma (UC) will receive PF-07209960 at the recommended dose from Part 1
  • PF-07209960

Eligibility Criteria

        Inclusion Criteria:

          -  Histological/cytological diagnosis of selected locally advanced or metastatic solid
             tumor

          -  Demonstrated radiographic progression on most recent tumor assessment imaging

          -  Have ≥1 measurable lesion as defined by RECIST 1.1 that has not been previously
             irradiated

          -  Eastern Cooperative Oncology Group performance status 0-2 for Part 1 and 0-1 for Part
             2

          -  Adequate hematologic, renal, liver, and coagulation functions

          -  LVEF ≥50% by echocardiogram or MUGA

          -  Resolved acute effects of any prior therapy

          -  Participants in Dose Expansion (Part 2) must have ≥2 prior lines of standard of care
             therapy

          -  Able to provide tumor tissue for submission to the Sponsor, including mandatory
             pre-treatment tumor biopsy (adequate archival tissue within the past 1 year is
             accepted in lieu of new biopsy) for all participants. Participants in Part 2 must also
             be able to undergo new (de novo) tumor biopsy at baseline (pre-treatment) and
             on-treatment biopsy until the Sponsor deems that an adequate number of biopsied
             samples have been received.

        Exclusion Criteria:

          -  Known active symptomatic brain or leptomeningeal metastases requiring steroids.

          -  Other active malignancy within 3 years prior to enrollment, except for adequately
             treated basal cell or squamous cell skin cancer, or carcinoma in situ

          -  Major surgery or radiation therapy within 4 weeks prior to planned first dose

          -  Last systemic anti-cancer therapy within 4 weeks prior to planned first dose (6 weeks
             for mitomycin C or nitrosoureas). Participants who received anti-PD-1 therapy require
             an interval of 90 days prior to first dose

          -  Participation in other studies involving investigational drug(s) within 4 weeks prior
             to planned first dose

          -  Active and clinically significant bacterial, fungal, or viral infection; Hepatitis B
             or Hepatitis C infection, AIDS-related illness (HIV+ and in good immune health as
             defined in the protocol may be eligible)

          -  Active COVID-19/SARS-CoV2

          -  Anticoagulation with vitamin K antagonists is not allowed

          -  Active bleeding disorder in the past 6 months prior to first dose

          -  History of clinically significant severe immune mediated adverse event that was
             considered related to prior immune modulatory therapy and required immunosuppressive
             therapy (other than hormone replacement therapy)

          -  History of interstitial lung disease or pneumonitis

          -  Organ transplant requiring immunosuppressive treatment or prior allogeneic bone marrow
             or hematopoietic stem cell transplant

          -  Pregnant or breastfeeding female participant
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with dose limiting toxicities (DLTs) in Dose Escalation (Part 1)
Time Frame:Baseline through 28 days after first dose (Cycle 1)
Safety Issue:
Description:DLTs will be evaluated during Cycle 1 (a cycle is 28 days) in Part 1. The number of DLTs will be used to determine the optimal dose

Secondary Outcome Measures

Measure:ORR in Dose Escalation (Part 1)
Time Frame:Baseline through up to 2 years or until disease progression
Safety Issue:
Description:Tumor response based on RECIST 1.1
Measure:Single dose: Maximal concentration (Cmax)
Time Frame:Cycle 1 (each cycle is 28 days), Cycle 2, and Day 1 of each subsequent cycle, and at the End of Treatment visit, up to about 2 years
Safety Issue:
Description:PK assessment for PF-07209960
Measure:Single dose: Time to maximal plasma concentration (Tmax)
Time Frame:Cycle 1 (each cycle is 28 days), Cycle 2, and Day 1 of each subsequent cycle, and at the End of Treatment visit, up to about 2 years
Safety Issue:
Description:PK assessment for PF-07209960
Measure:Single dose: Area Under the Curve within one dosing interval (AUCtau)
Time Frame:Cycle 1 (each cycle is 28 days), Cycle 2, and Day 1 of each subsequent cycle, and at the End of Treatment visit, up to about 2 years
Safety Issue:
Description:PK assessment for PF-07209960
Measure:Multiple dose: Maximum observed steady state plasma concentration (Cmax,ss)
Time Frame:Cycle 1 (each cycle is 28 days), Cycle 2, and Day 1 of each subsequent cycle, and at the End of Treatment visit, up to about 2 years
Safety Issue:
Description:PK assessment for PF-07209960
Measure:Multiple dose: Time to reach Maximum Observed Steady State Plasma Concentration (Tmax,ss)
Time Frame:Cycle 1 (each cycle is 28 days), Cycle 2, and Day 1 of each subsequent cycle, and at the End of Treatment visit, up to about 2 years
Safety Issue:
Description:PK assessment for PF-07209960
Measure:Multiple dose: Area Under the curve within one dose interval at steady state (AUCtau,ss)
Time Frame:Cycle 1 (each cycle is 28 days), Cycle 2, and Day 1 of each subsequent cycle, and at the End of Treatment visit, up to about 2 years
Safety Issue:
Description:PK assessment for PF-07209960
Measure:Lowest concentration (Ctrough) reached before the next dose is administered
Time Frame:Cycle 1 (each cycle is 28 days), Cycle 2, and day 1 of each subsequent cycle, and at the End of Treatment visit, up to about 2 years
Safety Issue:
Description:PK assessment for PF-07209960
Measure:Immunogenicity in Expansion Cohorts (Part 2)
Time Frame:Cycle 1 (each cycle is 28 days), Cycle 2, and Day 1 of each subsequent cycle, and at the End of Treatment visit, up to about 2 years
Safety Issue:
Description:Incidence, titers, and endogenous IL-15 cross-reactivity of anti-drug antibody and neutralizing antibody against PF-07209960
Measure:Intratumor T cells in pre-treatment vs. on-treatment tumor biopsy samples in Expansion Cohorts (Part 2)
Time Frame:Baseline through start of Cycle 2
Safety Issue:
Description:Effect of PF-07209960 therapy on immune cells in tumor biopsies
Measure:Disease control rate (DCR)
Time Frame:Baseline through up to 2 years or until disease progression
Safety Issue:
Description:DCR as assessed using RECIST 1.1
Measure:Duration of response (DOR)
Time Frame:Baseline through up to 2 years or until disease progression
Safety Issue:
Description:DOR as assessed using RECIST 1.1
Measure:Time to progression (TTP)
Time Frame:Baseline through up to 2 years or until disease progression
Safety Issue:
Description:TTP as assessed using RECIST 1.1
Measure:Progression free survival (PFS)
Time Frame:Baseline through up to 2 years or until disease progression
Safety Issue:
Description:PFS as assessed using RECIST 1.1
Measure:Overall survival (OS) in the Expansion Cohorts (Part 2)
Time Frame:Baseline through up to 2 years
Safety Issue:
Description:Proportion of participants alive

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • PD-1
  • immune checkpoint inhibitor
  • IL-15
  • IL-2
  • cytokine
  • immunotherapy
  • Metastasis
  • advanced solid tumor
  • metastatic solid tumor

Last Updated

March 11, 2021