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

Renal Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04628780
• Other study ID #: C4011001
• Secondary ID: 2021-004587-10
• Status: Terminated
• Phase: Phase 1
• Start date: December 16, 2020
• Est. completion date: May 26, 2023

Study information

• Verified date: December 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 37
• Est. completion date: May 26, 2023
• Est. primary completion date: May 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Biological:
• PF-07209960
PD-1 targeted IL-15 mutein

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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
Primary	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	ORR in Dose Escalation (Part 1)	Tumor response based on RECIST 1.1	Baseline through up to 2 years or until disease progression
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	Disease control rate (DCR)	DCR as assessed using RECIST 1.1	Baseline through up to 2 years or until disease progression
Secondary	Duration of response (DOR)	DOR as assessed using RECIST 1.1	Baseline through up to 2 years or until disease progression
Secondary	Time to progression (TTP)	TTP as assessed using RECIST 1.1	Baseline through up to 2 years or until disease progression
Secondary	Progression free survival (PFS)	PFS as assessed using RECIST 1.1	Baseline through up to 2 years or until disease progression
Secondary	Overall survival (OS) in the Expansion Cohorts (Part 2)	Proportion of participants alive	Baseline through up to 2 years

External Links

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