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

• ClinicalTrials.gov Identifier: NCT04171141
• Recruitment Status: Recruiting
• First Posted: November 20, 2019
• Last Update Posted: February 21, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: November 8, 2019
• First Posted Date: November 20, 2019
• Last Update Posted Date: February 21, 2021
• Actual Study Start Date: November 19, 2019
• Estimated Primary Completion Date: October 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 18, 2019)

• Number of participants with Dose-limiting toxicities (DLT) in Cycle 1 [ Time Frame: Baseline up to 28 days ]
• Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities [ Time Frame: Baseline up to approximately 24 months ]
• Duration of Adverse Events (AEs) [ Time Frame: Baseline up to approximately 24 months ]
• Number of Participants With Adverse Events (AEs) According to Severity [ Time Frame: Baseline up to approximately 24 months ]
• Number of Participants With Adverse Events (AEs) According to Seriousness [ Time Frame: Baseline up to up to approximately 24 months ]
• Number of Participants With Adverse Events (AEs) by Relationship [ Time Frame: Baseline up to approximately 24 months ]
• Objective Response - Number of Participants With Objective Response for Dose Expansion (Part 2) [ Time Frame: Baseline (1st dosing) up to approximately 24 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 18, 2019)

• Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 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 [ Time Frame: Up to approximately 24 months ]
• Incidence of Anti-Drug Antibody (ADA) an Neutralizing Antibodies anti-PD1 [ Time Frame: Up to approximately 24 months ]
• Incidence of Anti-Drug Antibody (ADA) an Neutralizing Antibodies (Nab) for anti-VEGF [ Time Frame: Up to approximately 24 months ]
• Apparent Clearance (CL/F) [ Time Frame: 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 - ∞)] [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Baseline up to 24 months ]
• Objective Response - Number of Participants With Objective Response for Dose Finding portion [ Time Frame: Baseline up to 24 months ]
• Minimum Observed Plasma Trough Concentration (Cmin) [ Time Frame: 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 [ Time Frame: Baseline to measured progressive disease (up to 24 months) ]
• Duration of Response (DR) for Dose Expansion [ Time Frame: Baseline up to approximately 24 months ]
• Change from baseline of immune cells from tumor biopsies [ Time Frame: Baseline and Cycle 2, Day 1 (each cycle is 28 days) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors.
• Official Title: 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
• Brief Summary: A phase 1, open-label, dose escalation and expansion study of PF-07062119 in patients with selected advanced or metastatic gastrointestinal tumors
• Detailed Description: 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).
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Gastrointestinal Tumors
• Colorectal Adenocarcinomas
• Gastric Adenocarcinomas
• Esophageal Adenocarcinomas

Intervention

• Drug: PF-07062119
  PF-07062119
• Drug: Anti-PD1
  Anti-PD1 PF-06801591
• Drug: Anti-VEGF
  Anti-VEGF IV (bevacizumab)

Study Arms

• Experimental: Dose Escalation
  Single Agent Dose Escalation
  Intervention: Drug: PF-07062119
• Experimental: Dose Finding Anti-PD-1 Combination
  Part 1B PF-07062119 plus anti-PD-1
  Interventions:

  • Drug: PF-07062119
  • Drug: Anti-PD1
• Experimental: Dose Finding anti-VEGF Combination
  Part 1B PF-07062119 plus anti-VEGF
  Interventions:

  • Drug: PF-07062119
  • Drug: Anti-VEGF
• Experimental: Dose Expansion Arm A
  PF-07062119 as a Single Agent in CRC
  Intervention: Drug: PF-07062119
• Experimental: Dose Expansion Arm B
  PF-07062119 in Combination with anti-PD-1 in CRC
  Intervention: Drug: PF-07062119
• Experimental: Dose Expansion Arm C
  PF-07062119 in Combination with anti-VEGF in CRC
  Interventions:

  • Drug: PF-07062119
  • Drug: Anti-PD1
  • Drug: Anti-VEGF
• Experimental: Dose Expansion Arm D
  PF-07062119 in Combination with either anti-PD-1 or anti-VEGF in various Tumor Types
  Interventions:

  • Drug: PF-07062119
  • Drug: Anti-PD1
  • Drug: Anti-VEGF

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 18, 2019): 110
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 1, 2023
• Estimated Primary Completion Date: October 1, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Pfizer CT.gov Call Center; 1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

• Listed Location Countries: Japan, United States

Administrative Information

• NCT Number: NCT04171141
• Other Study ID Numbers: C3861001; GUCY2C ( Other Identifier: Alias Study Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: February 2021