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

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

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.

Study Overview

• Status: Terminated
• Conditions: Renal Cell Carcinoma; Non-small-cell Lung Cancer; Squamous Cell Carcinoma of the Head and Neck; Urothelial Carcinoma; Colorectal Carcinoma; Ovarian Carcinoma
• Intervention / Treatment: Biological: PF-07209960

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Duarte, California, United States, 91010
      • City of Hope Investigational Drug Service (IDS)
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA Hematology/Oncology
    • Santa Monica, California, United States, 90404
      • Santa Monica UCLA Medical Center & Orthopaedic Hospital
    • Santa Monica, California, United States, 90404
      • UCLA Hematology Oncology - Santa Monica
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology PLLC
    • Nashville, Tennessee, United States, 37203
      • TriStar Centennial Medical center
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Research Institute/Tennessee Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center- Investigational Pharmacy
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology
    • San Antonio, Texas, United States, 78229
      • Christus Santa Rosa Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	Objective Response Rate (ORR) is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per RECIST version 1.1. CR: Complete disappearance of all target and non-target lesions with the exception of nodal disease; all target and non-target nodes must decrease to normal size (short axis <10 mm); all lesions must be assessed. PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; all target lesions must be assessed. Non-target PR lesions must be non-progressive disease (PD), where PD is unequivocal progression of pre-existing lesions.	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	Immunogenicity blood samples were assayed for ADA using a validated assay. The sample analysis followed a tiered approach of screening, confirmation, and titer determination. Samples tested positive for ADA were further analyzed for neutralizing antibodies (Nab) using a validated assay. Baseline is defined as pre-dose measurement on Day 1. n=Number of ADA evaluable participants with positive ADA at baseline; n1=Number of ADA evaluable participants with positive ADA at baseline but did not become boosted post-treatment; n2=Number of ADA-positive participants (treatment-induced or treatment-boosted).	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	Immunogenicity blood samples were assayed for ADA using a validated assay. The sample analysis followed a tiered approach of screening, confirmation, and titer determination. Samples tested positive for ADA were further analyzed for neutralizing antibodies (Nab) using a validated assay. Baseline is defined as pre-dose measurement on Day 1. n=Number of ADA evaluable participants with positive ADA at baseline; n2=Number of ADA-positive participants.	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	Immunogenicity blood samples were assayed for ADA using a validated assay. The sample analysis followed a tiered approach of screening, confirmation, and titer determination. Samples tested positive for ADA were further analyzed for neutralizing antibodies (NAb) using a validated assay. Baseline is defined as pre-dose measurement on Day 1. N1=Number of participants with ≥ 1 post-treatment NAb result; n=Number of NAb evaluable participants with positive NAb at baseline; n2=Number of NAb-positive participants (treatment induced).	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	TTP is defined as the time from start date of treatment to the date of the first documentation of PD or censoring. TTP is similar to PFS except that death is not treated as an event and is censored. Both new anti-cancer therapy given prior to PD and no PD by the end of follow-up are censoring events	Baseline through up to 2 years or until disease progression
Duration of Response (DOR) Based on Investigator Assessment in Participants With Confirmed Response	DOR is defined as the time from first documentation of CR or PR to date of first documentation of objective progression, or death due to any cause, or time of censoring, whichever occurred first.	Baseline through up to 2 years or until disease progression
Progression-Free Survival (PFS) Based on Investigator Assessment in Participants	PFS is defined as time from start date of treatment to the date of first documentation of PD or death due to any cause, or censoring, whichever occurred first. Both new anti-cancer therapy given prior to PD or death and no PD by the end of follow-up are censoring events.	Baseline through up to 2 years or until disease progression
Percentage of Participants With Disease Control Based on Investigator Assessment	Disease control rate (DCR) is defined as the percentage of participants with a BOR of CR, PR, non-CR/non-PD or SD.	From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 2 years approximately)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2020
• Primary Completion (Actual): May 3, 2023
• Study Completion (Actual): May 26, 2023

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 9, 2020
• First Posted (Actual): November 16, 2020

Study Record Updates

• Last Update Posted (Actual): July 29, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: immunotherapy; PD-1; IL-2; advanced solid tumor; metastatic solid tumor; cytokine; immune checkpoint inhibitor; IL-15; Metastasis
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Kidney Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Carcinoma, Squamous Cell; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma; Colorectal Neoplasms; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: C4011001; 2021-004587-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No