Study to Test the Safety and Tolerability of PF-07257876 in Participants With Selected Advanced Tumors.

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04881045

Collaborator

(none)

Enrollment

Locations

Arms

46.7

Anticipated Duration (Months)

2.3

Patients Per Site

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-07257876, a CD47-PD-L1 bispecific antibody, in participants with selected advanced or metastatic tumors for whom no standard therapy is available. The study contains 2 parts, single agent Dose Escalation (Part 1) to determine the recommended dose of PF-07257876, 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 Ovarian Cancer	Biological: PF-07257876	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 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 EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07257876 IN PATIENTS WITH ADVANCED OR METASTATIC TUMORS

Actual Study Start Date :

Aug 18, 2021

Anticipated Primary Completion Date :

Jul 8, 2025

Anticipated Study Completion Date :

Jul 8, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation (Part 1) Participants will receive PF-07257876 at escalating dose levels.	Biological: PF-07257876 CD47-PDL-1 bispecific antibody
Experimental: Dose Expansion (Part 2) - Cohort 1 (NSCLC) Participants with non-small cell lung cancer (NSCLC) will receive PF-07257876 at the recommended dose from Part 1.	Biological: PF-07257876 CD47-PDL-1 bispecific antibody
Experimental: Dose Expansion (Part 2) - Cohort 2 (SCCHN) Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive PF-07257876 at the recommended dose from Part 1.	Biological: PF-07257876 CD47-PDL-1 bispecific antibody

Arm

Intervention/Treatment

Experimental: Dose Escalation (Part 1)

Participants will receive PF-07257876 at escalating dose levels.

Biological: PF-07257876

CD47-PDL-1 bispecific antibody

Experimental: Dose Expansion (Part 2) - Cohort 1 (NSCLC)

Participants with non-small cell lung cancer (NSCLC) will receive PF-07257876 at the recommended dose from Part 1.

Biological: PF-07257876

CD47-PDL-1 bispecific antibody

Experimental: Dose Expansion (Part 2) - Cohort 2 (SCCHN)

Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive PF-07257876 at the recommended dose from Part 1.

Biological: PF-07257876

CD47-PDL-1 bispecific antibody

Outcome Measures

Primary Outcome Measures

Number of participants with dose limiting toxicities (DLTs) in Dose Escalation (Part 1) [Baseline through end of Cycle 1 (each cycle is 28 days)]
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 characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0), timing, seriousness, and relationship to study therapy.
Number of participants with clinically significant laboratory abnormalities [Baseline through up to 2 years]
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 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 Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Secondary Outcome Measures

Single dose Pharmacokinetics (PK) parameter: Maximal concentration (Cmax) in Part 1 [Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years]
Maximum observed plasma concentration of PF-07257876 (Cmax)
Single dose PK parameter: Time to maximal plasma concentration (Tmax) in Part 1 [Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years]
Time to maximal observed plasma concentration of PF-07257876 (Tmax)
Single dose PK parameter: Area under the Curve (AUClast) in Part 1 [Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years]
Area under the concentration-time curve from time zero to the last quantifiable time point prior to the next dose.
Multiple dose PK parameter: Maximal concentration (Cmax, ss) in Part 1 [Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years]
Maximum observed steady state plasma concentration of PF-07257876 (Cmax, ss)
Multiple dose PK parameter: Time to maximal plasma concentration (Tmax, ss) in Part 1 [Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years]
Time to reach Maximum Observed Steady State Plasma Concentration (Tmax,ss).
Multiple dose PK parameter: Area under the Curve (AUCtau, ss) in Part 1 [Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years]
Area Under the curve within one dose interval at steady state (AUCtau,ss)
Immunogenicity of PF-07257876 [Cycle 1, Cycle 2, Cycle 3, Cycle 4, and pre-dose on Day 1 at Cycle 5 and every third cycle thereafter (all cycles are 28 days) and at End of Treatment, up to 2 years]
Incidence, titers, and duration (if data permit) of antidrug antibodies (ADA) and neutralizing antibodies against PF-07257876
Intratumor T cell levels [Baseline through Cycle 2 Day 15 (each cycle is 28 days)]
Immune biomarker levels in archival biopsies and/or de novo and on-treatment tumor biopsies.
Intratumor PD-L1 expression [Baseline through Cycle 2 Day 15 (each cycle is 28 days)]
PD-L1 expression levels in pretreatment tumor biopsies
ORR in Dose Escalation (Part 1) [Baseline through up to 2 years or until disease progression]
Tumor response assessment based on RECIST 1.1
Duration of response (DOR) [Baseline through up to 2 years or until disease progression]
DOR 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
Time to progression (TTP) [Baseline through up to 2 years or until disease progression]
TTP as assessed using RECIST 1.1
Lowest concentration (Ctrough) reached before the next dose is administered in Part 2 [Pre-dose on Day 1 at Cycles 1, 2, 3, 4, 5 and every third cycle thereafter (each cycle is 28 days) and End of Treatment visit, up to 2 years]
PK assessment for PF-07257876
Overall Survival (OS) in the Expansion Cohorts (Part 2) [Baseline through up to 2 years or until disease progression]
Proportion of patients 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 advanced or metastatic tumor
Prior treatment with PD-1 (Programmed cell death 1) or PD-L1 (programmed death-ligand

in NSCLC and SCCHN or platinum-based therapy in Ovarian cancer

Confirmed radiographic progression of disease
PD-L1 IHC positivity ≥1%
Have ≥1 measurable lesion as defined by RECIST 1.1 that has not been previously irradiated
Eastern Cooperative Oncology Group performance status 0-1
Adequate hematologic, renal and liver functions
Resolved acute effects of any prior therapy
Participants in Part 1 must be able to provide archival tumor tissue collected within the prior 6 months or consent to undergo a fresh biopsy during screening. Participants enrolled to the MTD (Maximum Tolerated Dose) cohort in Part 1 must consent to mandatory paired pre-treatment and on-treatment biopsies. Participants in Part 2 must consent to a pre-treatment biopsy and a subset of patients must consent to a paired on-study biopsy as well until the Sponsor deems an adequate number have been received.

Exclusion Criteria:

Participants with known brain metastasis larger than 4 cm or that is symptomatic. New brain metastases detected at screening. Participants with previously diagnosed brain metastases are eligible if they have completed treatment and recovered from acute effects prior to study entry.
Abnormal neurological assessment by investigator
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 28 days or 5 half-lives (whichever is shorter) prior to planned first dose (6 weeks for mitomycin C or nitrosoureas)
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 idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (ie, bronchiolitis obliterans, cryptogenic organizing pneumonia), evidence of active pneumonitis on screening chest CT(computer tomography) scan
Anticoagulation with vitamin K antagonists or factor Xa inhibitors is not allowed
Treatment with chronic systemic corticosteroids or other immunosuppressive medications
Participation in other studies involving investigational drug(s) within 4 weeks prior to planned first dose
Active, uncontrolled bacterial, fungal, or viral infection, Hepatitis B, Hepatitis C, or Human immunodeficiency virus (HIV) infection
Active COVID-19/SARS-CoV2
Pregnant or breastfeeding female participant
Organ transplant requiring immunosuppressive treatment or prior allogeneic bone marrow or hematopoietic stem cell transplant
Significant cardiac or pulmonary conditions or events within previous 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
2	Mayo Clinic	Scottsdale	Arizona	United States	85259
3	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
4	Highlands Oncology Group	Rogers	Arkansas	United States	72758
5	Highlands Oncology Group	Springdale	Arkansas	United States	72762
6	Hoag Hospital Irvine	Irvine	California	United States	92618
7	The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate	Los Angeles	California	United States	90025
8	Keck Hospital of USC	Los Angeles	California	United States	90033
9	Keck School of Medicine of USC	Los Angeles	California	United States	90033
10	LAC+USC Medical Center	Los Angeles	California	United States	90033
11	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
12	Hoag Memorial Hospital Presbyterian	Newport Beach	California	United States	92663
13	Keck Medical Center of USC Pasadena	Pasadena	California	United States	91105
14	The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate (Emergency Back-Up Only)	Santa Monica	California	United States	90404
15	Mayo Clinic Jacksonville	Jacksonville	Florida	United States	32224
16	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
17	Siteman Cancer Center - West County	Creve Coeur	Missouri	United States	63141
18	Siteman Cancer Center-North County	Florissant	Missouri	United States	63031
19	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
20	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
21	Washington University	Saint Louis	Missouri	United States	63110
22	Siteman Cancer Center - South County	Saint Louis	Missouri	United States	63129
23	Siteman Cancer Center - St Peters	Saint Peters	Missouri	United States	63376
24	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
25	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
26	Duke Cancer Institute	Durham	North Carolina	United States	27710
27	UPMC Hillman Cancer Center - Camp Hill	Camp Hill	Pennsylvania	United States	17011
28	UPMC Hillman Cancer Center - Carlisle	Carlisle	Pennsylvania	United States	17015
29	UPMC Hillman Cancer Center Erie	Erie	Pennsylvania	United States	16505
30	UPMC Pinnacle - Community Osteopathic / Medical Sciences Pavilion (MSP)	Harrisburg	Pennsylvania	United States	17109
31	UPMC Pinnacle - Ortenzio Cancer Center (OCC)	Mechanicsburg	Pennsylvania	United States	17050
32	Magee-Womens Hospital of UPMC	Pittsburgh	Pennsylvania	United States	15213
33	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
34	UPMC Shadyside Hospital	Pittsburgh	Pennsylvania	United States	15232
35	UPMC Memorial	York	Pennsylvania	United States	17408
36	Rhode Island Hospital	Providence	Rhode Island	United States	02903
37	The Miriam Hospital	Providence	Rhode Island	United States	02906
38	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
39	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109