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

Study Overview
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Brief Summary
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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.

Official Title
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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

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

Intervention / Treatment
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* Biological: PF-07209960


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation (Part 1)<br>Participants will receive PF-07209960 at escalating dose levels | Biological: PF-07209960<br>* PD-1 targeted IL-15 mutein<br>|
| Experimental: Dose Expansion (Part 2) - Cohort 1 (NSCLC)<br>Participants with non-small cell lung cancer (NSCLC) will receive PF-07209960 at the recommended dose from Part 1 | Biological: PF-07209960<br>* PD-1 targeted IL-15 mutein<br>|
| Experimental: Dose Expansion (Part 2) - Cohort 2 (RCC)<br>Participants with renal cell carcinoma (RCC) will receive PF-07209960 at the recommended dose from Part 1 | Biological: PF-07209960<br>* PD-1 targeted IL-15 mutein<br>|
| Experimental: Dose Expansion (Part 2) - Cohort 3 (UC)<br>Participants with urothelial carcinoma (UC) will receive PF-07209960 at the recommended dose from Part 1 | Biological: PF-07209960<br>* PD-1 targeted IL-15 mutein<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with dose limiting toxicities (DLTs) in Dose Escalation (Part 1) | 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 | Baseline through 28 days after first dose (Cycle 1) | 
| Number of participants with adverse events (AEs) | AEs as characterized by type, frequency, severity (graded by CTCAE v.5.0; CRS graded by ASTCT criteria), timing, seriousness, and relationship to study drug | Baseline through up to 2 years | 
| Number of participants with clinically significant laboratory abnormalities | Laboratory abnormalities as characterized by type, frequency, severity (graded by CTCAE v.5.0), and timing | Baseline through up to 2 years | 
| Objective response rate (ORR) in the Expansion cohorts (Part 2) | Tumor response based on RECIST 1.1 | Baseline through up to 2 years or until disease progression | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD-1, immune checkpoint inhibitor, IL-15, IL-2, cytokine, immunotherapy, Metastasis, advanced solid tumor, metastatic solid tumor