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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Non-small-cell Lung Cancer
- Sponsor
- Pfizer
- Enrollment
- 37
- Locations
- 13
- Primary Endpoint
- Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=1 During the On-Treatment Period
- Status
- Terminated
- Last Updated
- last year
Overview
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.
Investigators
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)
Outcomes
Primary Outcomes
Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=1 During the On-Treatment Period
Time Frame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
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.
Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=3 During the On-Treatment Period
Time Frame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
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).
Number of Participants With TEAEs Leading to Death
Time Frame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
TEAEs were those events with onset dates occurring during the on-treatment period.
Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=3 During the On-Treatment Period
Time Frame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
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.
Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Cycle 1 (28 days)
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.
Number of Participants With Maximum Grade 3 or 4 TEAEs
Time Frame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
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.
Number of Participants With Serious TEAEs
Time Frame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
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.
Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=1 During the On-Treatment Period
Time Frame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
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.
Number of Participants Discontinued From Study Due to TEAEs
Time Frame: From start of the treatment until a minimum of 90 days after the last dose of study intervention (maximum up to 16.6 months)
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).
Secondary Outcomes
- 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))
- 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))
- Time to Progression (TTP) in Participants With Progressive Disease Based on Investigator Assessment(Baseline through up to 2 years or until disease progression)
- 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))
- Progression-Free Survival (PFS) Based on Investigator Assessment in Participants(Baseline through up to 2 years or until disease progression)
- Duration of Response (DOR) Based on Investigator Assessment in Participants With Confirmed Response(Baseline through up to 2 years or until disease progression)
- Percentage of Participants With Disease Control Based on Investigator Assessment(From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 2 years approximately))