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

• ClinicalTrials.gov Identifier: NCT04628780
• Recruitment Status: Recruiting
• First Posted: November 16, 2020
• Last Update Posted: September 21, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non-small-cell Lung Cancer; Squamous Cell Carcinoma of the Head and Neck; Renal Cell Carcinoma; Urothelial Carcinoma; Colorectal Carcinoma; Ovarian Carcinoma	Biological: PF-07209960	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 172 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 16, 2020
• Estimated Primary Completion Date: October 18, 2023
• Estimated Study Completion Date: March 22, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of participants with dose limiting toxicities (DLTs) in Dose Escalation (Part 1) [ Time Frame: Baseline through 28 days after first dose (Cycle 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
2. Number of participants with adverse events (AEs) [ Time Frame: Baseline through up to 2 years ]
   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
3. Number of participants with clinically significant laboratory abnormalities [ Time Frame: Baseline through up to 2 years ]
   Laboratory abnormalities as characterized by type, frequency, severity (graded by CTCAE v.5.0), and timing
4. Objective response rate (ORR) in the Expansion cohorts (Part 2) [ Time Frame: Baseline through up to 2 years or until disease progression ]
   Tumor response based on RECIST 1.1

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Pfizer CT.gov Call Center; 1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

Locations

United States, California

City of Hope Investigational Drug Service (IDS); Recruiting

Duarte, California, United States, 91010

City of Hope; Recruiting

Duarte, California, United States, 91010

Ronald Reagan UCLA Medical Center; Recruiting

Los Angeles, California, United States, 90095

UCLA Hematology/Oncology; Recruiting

Los Angeles, California, United States, 90095

Santa Monica UCLA Medical Center & Orthopaedic Hospital; Recruiting

Santa Monica, California, United States, 90404

UCLA Hematology Oncology - Santa Monica; Recruiting

Santa Monica, California, United States, 90404

United States, Tennessee

The Sarah Cannon Research Institute/Tennessee Oncology; Recruiting

Nashville, Tennessee, United States, 37203

TriStar Centennial Medical Center; Recruiting

Nashville, Tennessee, United States, 37203

United States, Texas

The University of Texas MD Anderson Cancer Center- Investigational Pharmacy; Recruiting

Houston, Texas, United States, 77030

The University of Texas MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Christus Santa Rosa Hospital; Recruiting

San Antonio, Texas, United States, 78229

NEXT Oncology; Recruiting

San Antonio, Texas, United States, 78229

United States, Washington

Seattle Cancer Care Alliance; Not yet recruiting

Seattle, Washington, United States, 98109

University of Washington Medical Center; Not yet recruiting

Seattle, Washington, United States, 98195

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT04628780
• Other Study ID Numbers: C4011001
• First Posted: November 16, 2020
• Last Update Posted: September 21, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:

PD-1; immune checkpoint inhibitor; IL-15; IL-2; cytokine; immunotherapy; Metastasis; advanced solid tumor; metastatic solid tumor

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Squamous Cell Carcinoma of Head and Neck; Colorectal Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma, Squamous Cell; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Kidney Diseases; Urologic Diseases; Head and Neck Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases