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

Sponsor

Pfizer (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04628780

Collaborator

(none)

Enrollment

Locations

Arms

38.3

Anticipated Duration (Months)

3.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

Actual Enrollment :

37 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential 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 :

Dec 16, 2020

Anticipated Primary Completion Date :

Feb 25, 2024

Anticipated Study Completion Date :

Feb 25, 2024

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

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

Secondary Outcome Measures

ORR in Dose Escalation (Part 1) [Baseline through up to 2 years or until disease progression]
Tumor response based on RECIST 1.1
Single dose: Maximal concentration (Cmax) [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
Single dose: Time to maximal plasma concentration (Tmax) [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
Single dose: Area Under the Curve within one dosing interval (AUCtau) [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
Multiple dose: Maximum observed steady state plasma concentration (Cmax,ss) [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
Multiple dose: Time to reach Maximum Observed Steady State Plasma Concentration (Tmax,ss) [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
Multiple dose: Area Under the curve within one dose interval at steady state (AUCtau,ss) [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
Lowest concentration (Ctrough) reached before the next dose is administered [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
Immunogenicity in Expansion Cohorts (Part 2) [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
Intratumor T cells in pre-treatment vs. on-treatment tumor biopsy samples in Expansion Cohorts (Part 2) [Baseline through start of Cycle 2]
Effect of PF-07209960 therapy on immune cells in tumor biopsies
Disease control rate (DCR) [Baseline through up to 2 years or until disease progression]
DCR as assessed using RECIST 1.1
Duration of response (DOR) [Baseline through up to 2 years or until disease progression]
DOR as assessed using RECIST 1.1
Time to progression (TTP) [Baseline through up to 2 years or until disease progression]
TTP as assessed using RECIST 1.1
Progression free survival (PFS) [Baseline through up to 2 years or until disease progression]
PFS as assessed using RECIST 1.1
Overall survival (OS) in the Expansion Cohorts (Part 2) [Baseline through up to 2 years]
Proportion of participants alive

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Investigational Drug Service (IDS)	Duarte	California	United States	91010
2	City of Hope	Duarte	California	United States	91010
3	Ronald Reagan UCLA Medical Center	Los Angeles	California	United States	90095
4	UCLA Hematology/Oncology	Los Angeles	California	United States	90095
5	Santa Monica UCLA Medical Center & Orthopaedic Hospital	Santa Monica	California	United States	90404
6	UCLA Hematology Oncology - Santa Monica	Santa Monica	California	United States	90404
7	The Sarah Cannon Research Institute/Tennessee Oncology	Nashville	Tennessee	United States	37203
8	TriStar Centennial Medical Center	Nashville	Tennessee	United States	37203
9	The University of Texas MD Anderson Cancer Center- Investigational Pharmacy	Houston	Texas	United States	77030
10	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
11	Christus Santa Rosa Hospital	San Antonio	Texas	United States	78229
12	NEXT Oncology	San Antonio	Texas	United States	78229