C4431001: A Study of PF-07260437 in Advanced or Metastatic Solid Tumors

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05067972

Collaborator

(none)

100

Enrollment

Locations

Arms

41.2

Anticipated Duration (Months)

14.3

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of PF-07260437, a B7-H4 x CD3 bispecific mAb, in participants aged ≥18 years of age with advanced or metastatic breast cancer, ovarian cancer or endometrial cancer. Adult participants with other advanced or metastatic high B7-H4 expressing tumors may be considered after discussion with and approval from sponsor.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Neoplasms Endometrial Neoplasms Breast Neoplasms	Drug: PF-07260437 Diagnostic Test: B7-H4 IHC	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 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 THE SAFETY, TOLERABILITY, PHARMACOKINETIC, PHARMACODYNAMIC, AND ANTITUMOR ACTIVITY OF PF-07260437 IN ADVANCED OR METASTATIC SOLID TUMORS

Actual Study Start Date :

Oct 7, 2021

Anticipated Primary Completion Date :

Mar 13, 2025

Anticipated Study Completion Date :

Mar 13, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Monotherapy dose escalation (Part 1) Participants will receive PF-07260437	Drug: PF-07260437 B7-H4 x CD3 bi-specific mAb Other Names: B7-H4
Experimental: Dose Expansion (Part 2A) - Tumor specific Arm A Participants will receive PF-07260437	Drug: PF-07260437 B7-H4 x CD3 bi-specific mAb Other Names: B7-H4 Diagnostic Test: B7-H4 IHC B7-H4 expression
Experimental: Dose Expansion (Part 2B) - Tumor specific Arm B Participants will receive PF-07260437	Drug: PF-07260437 B7-H4 x CD3 bi-specific mAb Other Names: B7-H4 Diagnostic Test: B7-H4 IHC B7-H4 expression
Experimental: Dose Expansion (Part 2C) - Tumor specific Arm C Participants will receive PF07260437	Drug: PF-07260437 B7-H4 x CD3 bi-specific mAb Other Names: B7-H4 Diagnostic Test: B7-H4 IHC B7-H4 expression

Outcome Measures

Primary Outcome Measures

Number of participants with dose limiting toxicities (DLTs) in Dose escalation [Baseline through 28 days after first dose]
DLTs will be evaluated in Part 1. The number of DLTs will be used to determine the dose escalation decision and recommended dose of PF-07260437
Number of participants with adverse events [Baseline through up to 2 years]
Number of participants with clinically significant laboratory abnormalities [Baseline through 2 years]
Number of participants with clinical adverse events at the recommended dose for expansion [Baseline through up to 2 years]
Number of participants with clinically significant laboratory abnormalities at recommended dose for expansion [Baseline through 2 years]

Secondary Outcome Measures

Number of participants with immune related adverse events [Baseline through 90 days]
Single dose: Maximal concentration (Cmax) [Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years]
PK assessment for PF-07260437
Time to maximal plasma concentration (Tmax) [Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years]
PK assessment of PF-07260437
Single dose: Area Under the Curve (AUClast) [Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years]
PK assessment of PF-07260437
Plasma Decay Half-live (t1/2) [Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years]
PK assessment of PF-07260437
Area Under the Curve from Time Zero to Extrapolated Infinite Time (AUCinf) [Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years]
PK assessment of PF-07260437
Apparent Volume of Distribution (Vz/F) [Cycle 1 (each cycle is 28 days) Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years]
PK assessment of PF-0260347
Accumulation Ratio (Rac) [Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3 and Day 1 of each subsequent cycle through end of treatment, up to about 2 years]
PK assessment for PF-07260437
Apparent Oral Clearance (CL/F) [Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years]
PF assessment of PF-07260437
Apparent Oral Clearance of Study Drug (CLss/F) [Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day of each subsequent cycle through end of treatment, up to about 2 years]
PK assessment for PF-07260437
Area under the curve at steady state under a dosing interval (AUCss,τ) [Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years]
PK assessment of PF-07260437
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) [Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years]
PK assessment of PF-07260437
Time to reach maximum Observed Plasma Concentration at Steady State (Tmax,ss) [Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent Cycle through end of treatment, up to about 2 years]
PK assessment of PF-07260437
Minimum Observed Plasma Trough Concentration at Steady State (Cmin,ss) [Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3 and Day 1 of each subsequent cycle through end of treatment, up to about 2 years.]
PK assessment for PF-07260437
Incident and titers of anti-body drug antibody against PF-07260437 [Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years]
Immunogenicity of PF-07260437
Incident and titers of anti-body neutralizing antibody against PF-07260437 [Cycle 1 (each cycle is 28 days), Cycle 2, Cycle 3, and Day 1 of each subsequent cycle through end of treatment, up to about 2 years]
Immunogenicity of PF-07260437
Number of participants with immune related adverse events at the recommended dose for expansion [Baseline through up to 2 years]
Duration of response (DOR) in dose expansion [Baseline through up to 2 years or until disease progression]
DOR as assessed using RECIST 1.1 and irRECIST
Time to progression (TTP) in dose expansion [Baseline through up to 2 years or until disease progression]
TTP as assessed using RECIST 1.1 and irRECIST
Objective response rate (ORR) in dose expansion [Baseline through up to 2 years or until disease progression]
ORR as assessed using RECIST 1.1 and irRECIST
Progression free survival (PFS) [Baseline through up to 2 years or until disease progression]
PFS as assessed using RECIST 1.1 and irRECIST
Overall survival (OS) in the Expansion Cohorts (Part 2) [Baseline through up to 2 years]
Proportion of participants alive
Phenotypes and quantity of tumor infiltrating lymphocytes (TIL) before and after PF-07260437 treatment [28 days prior to first dose and 7 days within Cycle 2, Day 15 of PF-07260437]
Immune Cells assessments from paired biopsies

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Part 1: Histological/cytological diagnosis of selected locally advanced or metastatic breast cancer, endometrial cancer and ovarian cancer
Part 2A:In second line or more, participants with histological/cytological diagnosis of locally advanced or metastatic HR+ HER2- breast cancer showing high B7-H4 expression
Part 2B: In second line or more participants with histological or cytological diagnosis of locally advance or metastatic HR+ Her2- breast cancer or triple negative breast cancer (TNBC) with no biomarker pre-selection
Part 2C: In second line or more participants with histological diagnosis of locally advance or metastatic triple negative breast cancer with high B7-H4 expression
Thyroid function within normal laboratory range; in participants with abnormal thyroid function if Free T4 is normal and participant is clinically euthyroid, participants is eligible

Exclusion Criteria:

Participants with any active malignancy within 3 years prior to enrollment
Participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including participants with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement).
History of Grade ≥3 immune mediated adverse events (including liver function tests that where considered drug related and cytokine release syndrome) that was considered related to prior immune modulatory therapy (eg, immune checkpoint inhibitors, co stimulatory agents, etc.) and required immunosuppressive therapy within 1 year of treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope (City of Hope National Medical Center, City of Hope Medical Center)	Duarte	California	United States	91010
2	Moffitt Cancer Center	Tampa	Florida	United States	33612
3	Montefiore Einstein Center for Cancer Care	Bronx	New York	United States	10461
4	Montefiore Medical Center	Bronx	New York	United States	10461
5	NEXT Oncology	San Antonio	Texas	United States	78229
6	Swedish Cancer Institute	Seattle	Washington	United States	98104
7	Pan American Center for Oncology Trials	Rio Piedras		Puerto Rico	00935