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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Ovarian Neoplasms, Endometrial Neoplasms, Breast Neoplasms

Intervention / Treatment
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* Drug: PF-07260437
* Diagnostic Test: B7-H4 IHC


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with dose limiting toxicities (DLTs) in Dose escalation | 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 | Baseline through 28 days after first dose | 
| 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

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer of Endometrium, Cancer of the Endometrium, Carcinoma of Endometrium, Endometrial Cancer, Endometrial Carcinoma, Endometrium Cancer, Neoplasms, Endometrial, Cancer of Ovary, Cancer of the Ovary, Neoplasms, Ovarian, Ovarian Cancer, Ovary Cancer, Ovary Neoplasms, Breast Cancer, Breast Carcinoma, Breast Tumors, Cancer of Breast, Cancer of the Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Malignant Tumor of Breast