Clinical trial NCT04628780: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-small-cell Lung Cancer
Squamous Cell Carcinoma of the Head and Neck
Renal Cell Carcinoma
Urothelial Carcinoma
Colorectal Carcinoma
Ovarian Carcinoma
Keywords: PD-1
immune checkpoint inhibitor
IL-15
IL-2
cytokine
immunotherapy
Metastasis
advanced solid tumor
metastatic solid tumor
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-11-16
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (28 days)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
measure: Number of Participants With Maximum Grade 3 or 4 TEAEs
timeFrame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
measure: Number of Participants With TEAEs Leading to Death
timeFrame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
measure: Number of Participants With Serious TEAEs
timeFrame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
measure: Number of Participants Discontinued From Study Due to TEAEs
timeFrame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
measure: Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=1 During the On-Treatment Period
timeFrame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
measure: Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=3 During the On-Treatment Period
timeFrame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
measure: Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=1 During the On-Treatment Period
timeFrame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
measure: Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=3 During the On-Treatment Period
timeFrame: 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:
measure: Percentage of Participants With Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: 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)
measure: Number of Participants by Antidrug Antibody (ADA) Categories
timeFrame: 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)
measure: Number of Participants by ADA Against Endogenous IL-15 Wild-type Categories
timeFrame: 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)
measure: Number of Participants by Anti-IL-15 Wild Type NAb Categories
timeFrame: 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)
measure: Time to Progression (TTP) in Participants With Progressive Disease Based on Investigator Assessment
timeFrame: Baseline through up to 2 years or until disease progression
measure: Duration of Response (DOR) Based on Investigator Assessment in Participants With Confirmed Response
timeFrame: Baseline through up to 2 years or until disease progression
measure: Progression-Free Survival (PFS) Based on Investigator Assessment in Participants
timeFrame: Baseline through up to 2 years or until disease progression
measure: Percentage of Participants With Disease Control Based on Investigator Assessment
timeFrame: From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 2 years approximately)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Investigational Drug Service (IDS)
state: California
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Santa Monica
country: United States
facility: Santa Monica UCLA Medical Center & Orthopaedic Hospital
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology Oncology - Santa Monica
state: California
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute/Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: TriStar Centennial Medical Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center- Investigational Pharmacy
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Christus Santa Rosa Hospital
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: