Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors.

Study Overview
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Brief Summary
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A phase 1, open-label, dose escalation and expansion study of PF-07062119 in patients with selected advanced or metastatic gastrointestinal tumors

Detailed Description
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This is a Phase 1, open-label, multi-center, non-randomized, multiple dose, safety, tolerability, pharmacokinetic, and pharmacodynamic study of PF-07062119 administered as a single agent in sequential dose levels and then in combination with anti-programmed cell death -1 protein (anti-PD-1) and in combination with an anti-vascular endothelial growth factor (anti-VEGF). In Part 1A, successive cohorts of patients will receive escalating doses of PF-007062119 and then in dose finding (Part 1B) with PF-07062119 in combination with anti-PD-1 and in combination with anti-VEGF. This study contains 2 parts, dose escalation with single agent (Part 1A) and then dose finding with PF-007062119 in combination with ant-PD-1 and in combination with anti-VEGF (Part 1B) followed by dose expansion arms as a single agent and PF-07062119 in combination with anti-PD 1 and in combination with anti-VEGF (Part 2).

Official Title
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A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS AND ANTI TUMOR ACTIVITY OF PF-07062119 IN PATIENTS WITH ADVANCED GASTROINTESTINAL TUMORS

Conditions
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Gastrointestinal Tumors, Colorectal Adenocarcinomas, Gastric Adenocarcinomas, Esophageal Adenocarcinomas

Intervention / Treatment
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* Drug: PF-07062119
* Drug: Anti-PD1
* Drug: Anti-VEGF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Part 1 and Part 2, diagnosis of advanced/metastatic colorectal, gastric or esophageal adenocarcinoma that is resistant to standard therapy or for which no local regulatory approved standard therapy is available that would confer significant benefit. For Part 2, diagnosis of colorectal adenocarcinoma that is resistant to standard therapy or for which no standard therapy is available Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 Measurable disease or non-measurable disease and refractory to or intolerant of existing therapies (Part 1) Measurable disease as defined by RECIST 1.1 is required (Part 2) Exclusion Criteria: Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases Other active malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ Major surgery or radiation within 3 weeks prior to study entry Last anti-cancer treatment within 4 weeks prior to study entry Active or history of clinically significant autoimmune disease that required systemic immunosuppressive medication Active or history of clinically significant gastrointestinal disease Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry Pregnant or breastfeeding female patients

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: Dose Escalation<br>Single Agent Dose Escalation | Drug: PF-07062119<br>* PF-07062119<br>|
| Experimental: Dose Finding Anti-PD-1 Combination<br>Part 1B PF-07062119 plus anti-PD-1 | Drug: PF-07062119<br>* PF-07062119<br>Drug: Anti-PD1<br>* Anti-PD1 PF-06801591<br>|
| Experimental: Dose Finding anti-VEGF Combination<br>Part 1B PF-07062119 plus anti-VEGF | Drug: PF-07062119<br>* PF-07062119<br>Drug: Anti-VEGF<br>* Anti-VEGF IV (bevacizumab)<br>|
| Experimental: Dose Expansion Arm A<br>PF-07062119 as a Single Agent in CRC | Drug: PF-07062119<br>* PF-07062119<br>|
| Experimental: Dose Expansion Arm B<br>PF-07062119 in Combination with anti-PD-1 in CRC | Drug: PF-07062119<br>* PF-07062119<br>|
| Experimental: Dose Expansion Arm C<br>PF-07062119 in Combination with anti-VEGF in CRC | Drug: PF-07062119<br>* PF-07062119<br>Drug: Anti-PD1<br>* Anti-PD1 PF-06801591<br>Drug: Anti-VEGF<br>* Anti-VEGF IV (bevacizumab)<br>|
| Experimental: Dose Expansion Arm D<br>PF-07062119 in Combination with either anti-PD-1 or anti-VEGF in various Tumor Types | Drug: PF-07062119<br>* PF-07062119<br>Drug: Anti-PD1<br>* Anti-PD1 PF-06801591<br>Drug: Anti-VEGF<br>* Anti-VEGF IV (bevacizumab)<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 (DLT) in Cycle 1 |  | Baseline up to 28 days (or 42 days as applicable) | 
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities |  | Baseline up to approximately 24 months | 
| Duration of Adverse Events (AEs) |  | Baseline up to approximately 24 months | 
| Number of Participants With Adverse Events (AEs) According to Severity |  | Baseline up to approximately 24 months | 
| Number of Participants With Adverse Events (AEs) According to Seriousness |  | Baseline up to up to approximately 24 months | 
| Number of Participants With Adverse Events (AEs) by Relationship |  | Baseline up to approximately 24 months | 
| Objective Response - Number of Participants With Objective Response for Dose Expansion (Part 2) |  | Baseline (1st dosing) up to approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) |  | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Incidence of Anti-Drug Antibody (ADA) an Neutralizing Antibodies (Nab) for PF-07062119 |  | Up to approximately 24 months | 
| Incidence of Anti-Drug Antibody (ADA) an Neutralizing Antibodies anti-PD1 |  | Up to approximately 24 months | 
| Incidence of Anti-Drug Antibody (ADA) an Neutralizing Antibodies (Nab) for anti-VEGF |  | Up to approximately 24 months | 
| Apparent Clearance (CL/F) |  | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] |  | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Maximum Observed Plasma Concentration (Cmax) |  | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Terminal Half-Life (t1/2) |  | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Objective Response - Number of Participants With Objective Response for Dose Escalation |  | Baseline up to 24 months | 
| Objective Response - Number of Participants With Objective Response for Dose Finding portion |  | Baseline up to 24 months | 
| Minimum Observed Plasma Trough Concentration (Cmin) |  | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Progression-Free Survival (PFS) for Dose Expansion |  | Baseline to measured progressive disease (up to 24 months) | 
| Duration of Response (DR) for Dose Expansion |  | Baseline up to approximately 24 months | 
| Change from baseline of immune cells from tumor biopsies |  | Baseline and Cycle 2, Day 1 (each cycle is 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric cancer, Esophageal cancer, Colorectal cancer, Advanced esophageal cancer, Metastatic esophageal cancer, Advanced colorectal cancer, Metastatic gastric cancer, Advanced gastric cancer, Metastatic colorectal cancer, GUCY2c, Anti-PD1, Anti-VEGF, Measurable disease, PF-07062119, PF-06801591, Bevacizumab