NCT04628780

Brief Summary

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 Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
37

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Dec 2020

Typical duration for phase_1

Geographic Reach
1 country

13 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 9, 2020

Completed
7 days until next milestone

First Posted

Study publicly available on registry

November 16, 2020

Completed
1 month until next milestone

Study Start

First participant enrolled

December 16, 2020

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 3, 2023

Completed
23 days until next milestone

Study Completion

Last participant's last visit for all outcomes

May 26, 2023

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

July 29, 2024

Completed
Last Updated

July 29, 2024

Status Verified

February 1, 2024

Enrollment Period

2.4 years

First QC Date

November 9, 2020

Results QC Date

February 12, 2024

Last Update Submit

February 12, 2024

Conditions

Keywords

PD-1immune checkpoint inhibitorIL-15IL-2cytokineimmunotherapyMetastasisadvanced solid tumormetastatic solid tumor

Outcome Measures

Primary Outcomes (10)

  • Number of Participants With Dose Limiting Toxicities (DLTs)

    For the purpose of dose escalation, any of the following adverse events were classified as DLTs: Occur in the first cycle of treatment, or within 28 days after the start of the study treatment; and were at least possibly related to PF-07209960; A participant was classified as DLT evaluable if he/she experienced a DLT or if he/she otherwise in the absence of a DLT received 2 doses of the study intervention during Cycle 1 and had received all scheduled safety assessments during the DLT window. If a participant failed to meet these criteria, he/she might be replaced. Monitoring for DLTs occurred during Part 1.

    Cycle 1 (28 days)

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    Adverse event (AE) was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 90 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs).

    From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)

  • Number of Participants With Maximum Grade 3 or 4 TEAEs

    AE was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 90 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. TEAEs were graded by the investigator using National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 5.0 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with Maximum Grade 3 or 4 TEAEs were reported.

    From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)

  • Number of Participants With TEAEs Leading to Death

    TEAEs were those events with onset dates occurring during the on-treatment period.

    From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)

  • Number of Participants With Serious TEAEs

    TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment until a minimum of 90 days after the last dose of study intervention. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs). A serious TEAE was any untoward medical occurrence that at any dose resulted in any of following outcomes/considered to be an important medical event: death; life-threatening experience (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect.

    From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)

  • Number of Participants Discontinued From Study Due to TEAEs

    Participants who had an AE record that indicated that the AE caused the participant to be discontinued from the study. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment until a minimum of 90 days after the last dose of study intervention. Treatment-related AEs were those related to any study drug (ie, at least one of the study drugs).

    From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)

  • Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=1 During the On-Treatment Period

    The number of participants with newly occurring or worsening hematology abnormalities during the on-treatment period were summarized by worst grade on-treatment. NCI-CTCAE criteria version 5.0 is used. As per NCI CTCAE toxicity grading v5.0, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.

    From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)

  • Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=3 During the On-Treatment Period

    The number of participants with newly occurring or worsening hematology abnormalities during the on-treatment period were summarized by worst grade on-treatment. NCI-CTCAE criteria version 5.0 is used. As per NCI CTCAE toxicity grading v5.0, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.

    From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)

  • Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=1 During the On-Treatment Period

    The number of participants with newly occurring or worsening chemistry abnormalities during the on-treatment period were summarized by worst grade on-treatment. NCI-CTCAE criteria version 5.0 is used. As per NCI CTCAE toxicity grading v5.0, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.

    From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)

  • Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=3 During the On-Treatment Period

    The number of participants with newly occurring or worsening chemistry abnormalities during the on-treatment period were summarized by worst grade on-treatment. NCI-CTCAE criteria version 5.0 is used. As per NCI CTCAE toxicity grading v5.0, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.

    From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)

Secondary Outcomes (8)

  • Percentage of Participants With Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

    From start of the treatment until disease progression or discontinuation from study or death due to any cause, whichever occurred first (maximum up to 14.5 months)

  • Number of Participants by Antidrug Antibody (ADA) Categories

    on Day 1,15 and 22 of Cycle 1, on Day 1 of Cycles 2-9, and then on Day 1 of Cycles 12, 15, and at the end of treatment (EOT)

  • Number of Participants by ADA Against Endogenous IL-15 Wild-type Categories

    on Day 1,15 and 22 of Cycle 1, on Day 1 of Cycles 2-9, and then on Day 1 of Cycles 12, 15, and at the end of treatment (EOT)

  • Number of Participants by Anti-IL-15 Wild Type NAb Categories

    on Day 1,15 and 22 of Cycle 1, on Day 1 of Cycles 2-9, and then on Day 1 of Cycles 12, 15, and at the end of treatment (EOT)

  • Time to Progression (TTP) in Participants With Progressive Disease Based on Investigator Assessment

    Baseline through up to 2 years or until disease progression

  • +3 more secondary outcomes

Study Arms (4)

Dose Escalation (Part 1)

EXPERIMENTAL

Participants will receive PF-07209960 at escalating dose levels

Biological: PF-07209960

Dose Expansion (Part 2) - Cohort 1 (NSCLC)

EXPERIMENTAL

Participants with non-small cell lung cancer (NSCLC) will receive PF-07209960 at the recommended dose from Part 1

Biological: PF-07209960

Dose Expansion (Part 2) - Cohort 2 (RCC)

EXPERIMENTAL

Participants with renal cell carcinoma (RCC) will receive PF-07209960 at the recommended dose from Part 1

Biological: PF-07209960

Dose Expansion (Part 2) - Cohort 3 (UC)

EXPERIMENTAL

Participants with urothelial carcinoma (UC) will receive PF-07209960 at the recommended dose from Part 1

Biological: PF-07209960

Interventions

PF-07209960BIOLOGICAL

PD-1 targeted IL-15 mutein

Dose Escalation (Part 1)Dose Expansion (Part 2) - Cohort 1 (NSCLC)Dose Expansion (Part 2) - Cohort 2 (RCC)Dose Expansion (Part 2) - Cohort 3 (UC)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

City of Hope Investigational Drug Service (IDS)

Duarte, California, 91010, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UCLA Hematology/Oncology

Los Angeles, California, 90095, United States

Location

Santa Monica UCLA Medical Center & Orthopaedic Hospital

Santa Monica, California, 90404, United States

Location

UCLA Hematology Oncology - Santa Monica

Santa Monica, California, 90404, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

The Sarah Cannon Research Institute/Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

TriStar Centennial Medical Center

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center- Investigational Pharmacy

Houston, Texas, 77030, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Christus Santa Rosa Hospital

San Antonio, Texas, 78229, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Related Links

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungSquamous Cell Carcinoma of Head and NeckCarcinoma, Renal CellCarcinoma, Transitional CellColorectal NeoplasmsOvarian NeoplasmsNeoplasm Metastasis

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract DiseasesCarcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeHead and Neck NeoplasmsAdenocarcinomaKidney NeoplasmsUrologic NeoplasmsUrogenital NeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital DiseasesIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleGenital Neoplasms, FemaleGenital DiseasesEndocrine System DiseasesGonadal DisordersNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Limitations and Caveats

The study was planned to have 2 parts: a single agent dose escalation (Part 1) followed by a dose expansion (Part 2). Due to the early termination of the study, Part 2 study was never initiated and the overall study consisted of only Part 1. The data displayed are from the Part 1 study which is the only 1 period of the study. Besides, the pharmacokinetic (PK) endpoints of this study were not conducted. Therefore no results of PK parameters are displayed.

Results Point of Contact

Title
Pfizer ClinicalTrials.gov Call Center
Organization
Pfizer Inc.

Study Officials

  • Pfizer CT.gov Call Center

    Pfizer

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 9, 2020

First Posted

November 16, 2020

Study Start

December 16, 2020

Primary Completion

May 3, 2023

Study Completion

May 26, 2023

Last Updated

July 29, 2024

Results First Posted

July 29, 2024

Record last verified: 2024-02

Data Sharing

IPD Sharing
Will not share

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.

Locations