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

Phase 1TerminatedNCT04171141

Pfizer79 enrolled

Overview

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

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Gastrointestinal Tumors Colorectal Adenocarcinomas Gastric Adenocarcinomas Esophageal Adenocarcinomas

Interventions

PF-07062119DRUG

PF-07062119

Anti-PD1DRUG

Anti-PD1 PF-06801591

Anti-VEGFDRUG

Anti-VEGF IV (bevacizumab)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (19)

City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

Duarte, California, United States

Outcomes

Primary Outcomes

Number of Participants With Dose Limiting Toxicities (DLTs) Assessed Through Cycle 1

Hematological DLTs: * Grade 3 neutropenia lasting \>5 days * Febrile neutropenia defined as an ANC \<1.0 x 10 ̂9/L with a single temperature of \>38.3°C, or a sustained temperature of ≥38°C, for more than 1 hour * Grade ≥3 Neutropenia with infection * Grade 3 Thrombocytopenia with Grade ≥2 (clinically significant) bleeding * any Grade 4 Thrombocytopenia * Anemia or Thrombocytopenia requiring transfusion Non Hematological DLTs: * Grade ≥3 fatigue lasting ≥7 days * for participants with liver, bone, or lung metastasis, an AST or ALT increase \>8 x ULN or ALP \>10 x ULN; * confirmed DILI meeting Hy's law criteria * Grade 3 Vomiting or Diarrhea lasting ≥3 days despite adequate treatment/other supportive care * Grade 4 Vomiting or Diarrhea * Grade ≥3 CRS regardless of duration * Grade ≥3 QTcF prolongation irrespective of duration * any death not clearly due to underlying disease or extraneous causes Clinically important/persistent toxicities were DLTs reviewed by investigators and sponsor.

Time frame: 28 Days

Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs),Treatment-Emergent Serious Adverse Events (TESAEs), Maximum Grade 3 or 4 and 5 TEAEs

An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect, etc. Treatment-emergent events were with onset date occurring during the on-treatment period. AEs were documented and recorded at each visit using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

Time frame: 4 Years

Number of Participants With Treatment-Related TEAEs, TESAEs, Maximum Grade 3 or 4 and 5 TEAEs

An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect, etc. Treatment-emergent events were with onset date occurring during the on-treatment period. Relatedness to study treatment was determined by the investigator. AEs were documented and recorded at each visit using the NCI CTCAE version 5.0. Severe AEs were classified as Grade 3; life-threatening consequences and urgent intervention indicated were classified as Grade 4; deaths related to AEs were classified as Grade 5.

Data from ClinicalTrials.gov

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Secondary Outcomes

Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Maximum Concentration (Cmax) - Priming Cohorts

Cmax was observed directly from data.

Time frame: Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 4 Day 1

Cycle 1 and Cycle 4 PF-07062119 PK Parameters: Cmax - Non-Priming Cohorts

Cmax was observed directly from data.