PF-07062119 / Pfizer - LARVOL DELTA

Establishing a reverse translational platform to dissect mode of action and mechanisms of resistance to GUCY2C-CD3 T cell engager (AACR 2024) - "Here, we will discuss our efforts to perform immune profiling of T cell and myeloid tumor infiltrates, and to evaluate tumor cell depletion and cytokine production of colorectal carcinoma (CRC) samples treated ex vivo with PF-07062119. This platform may be leveraged to 1) provide clinically relevant disease insights to the effect of TCEs across a range of tumor indications; 2) determine impact of different combinatorial partners on tumor cell killing to inform clinical decisions; 3) address questions related to the minimal efficacy of TCEs in the solid tumor space; and 4) provide potential solutions for future combination partners to overcome immunosuppression in the tumor microenvironment."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • GUCY2C

Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors. (clinicaltrials.gov) - P1 | N=78 | Terminated | Sponsor: Pfizer | N=130 ➔ 78 | Trial completion date: Sep 2025 ➔ Nov 2023 | Recruiting ➔ Terminated | Trial primary completion date: Sep 2025 ➔ Nov 2023; Study was terminated due to strategic considerations and not due to safety.

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors. (clinicaltrials.gov) - P1 | N=130 | Recruiting | Sponsor: Pfizer | Trial completion date: Feb 2025 ➔ Sep 2025 | Trial primary completion date: Feb 2025 ➔ Sep 2025

Metastases • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

[VIRTUAL] A novel GUCY2C - CD3 bispecific engages T cells to induce cytotoxicity in gastrointestinal tumors (AACR-II 2020) - P1 | "These data highlight the potential for PF-07062119 to demonstrate efficacy and improve patient outcomes in CRC and other gastrointestinal malignancies. A clinical Phase I study has been initiated in patients with CRC, gastric and esophageal adenocarcinomas (NCT04171141)."

IO biomarker • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • Thoracic Cancer • BRAF • KRAS

Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors. (clinicaltrials.gov) - P1 | N=130 | Recruiting | Sponsor: Pfizer | Trial completion date: Jul 2024 ➔ Feb 2025 | Trial primary completion date: Jul 2024 ➔ Feb 2025

Metastases • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors. (clinicaltrials.gov) - P1 | N=130 | Recruiting | Sponsor: Pfizer | Trial completion date: Mar 2024 ➔ Jul 2024 | Trial primary completion date: Mar 2024 ➔ Jul 2024

Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors. (clinicaltrials.gov) - P1 | N=130 | Recruiting | Sponsor: Pfizer | Trial completion date: Jan 2024 ➔ Jun 2024 | Trial primary completion date: Jan 2024 ➔ Jun 2024

Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors. (clinicaltrials.gov) - P1; N=130; Recruiting; Sponsor: Pfizer; Trial completion date: Sep 2023 ➔ Jan 2024; Trial primary completion date: Sep 2023 ➔ Jan 2024

Clinical • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

Preclinical Evaluation of Zr-Df-IAB22M2C PET as an Imaging Biomarker for the Development of the GUCY2C-CD3 Bispecific PF-07062119 as a T Cell Engaging Therapy. (PubMed, Mol Imaging Biol) - "Immune-imaging technologies for quantitative cellular measures would be a valuable biomarker in immunotherapeutic clinical development. We demonstrated a qualification of Zr-IAB22M2C PET to evaluate PD responses (mice) to a novel immunotherapeutic."

IO biomarker • Journal • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • CD8

Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors. (clinicaltrials.gov) - P1; N=110; Recruiting; Sponsor: Pfizer; Trial completion date: Oct 2022 ➔ Aug 2023; Trial primary completion date: Oct 2022 ➔ Aug 2023

Clinical • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

Discovery and optimization of a novel anti-GUCY2c x CD3 bispecific antibody for the treatment of solid tumors. (PubMed, MAbs) - "Collectively, these improvements translated to a molecule with potent single-agent in vivo efficacy in a tumor cell line adoptive transfer model and a cynomolgus monkey pharmacokinetic profile (half-life>4.5 days) suitable for clinical development. Clinical evaluation of PF-07062119 is ongoing."

Journal • Oncology • Solid Tumor

Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors. (clinicaltrials.gov) - P1; N=110; Recruiting; Sponsor: Pfizer; Trial completion date: Mar 2023 ➔ Oct 2022; Trial primary completion date: Mar 2023 ➔ Oct 2022

Clinical • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

[VIRTUAL] Evaluation of GUCY2c-CD3 bispecific targeting GI cancers in an orthotopic colorectal tumor model (AACR-II 2020) - "These results demonstrate that PF-07062119 can eliminate LS1034 orthotopic tumors and potential metastasis with no observable toxicities. This supports our hypothesis that apical restriction of GUCY2c expression in normal intestine creates tumor-vs-normal differential for selective targeting of GUCY2c positive tumors, and the GUCY2c-CD3 bispecific antibody redirects T cells to lyse the CRC tumor cells."

Preclinical • Colon Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors. (clinicaltrials.gov) - P1; N=110; Recruiting; Sponsor: Pfizer; Trial completion date: Sep 2023 ➔ Jun 2023; Trial primary completion date: Sep 2023 ➔ Jun 2023

Clinical • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • Thoracic Cancer

A Novel GUCY2C-CD3 T cell Engaging Bispecific construct (PF-07062119) for the Treatment of Gastrointestinal Cancers. (PubMed, Clin Cancer Res) - "These data highlight the potential for PF-07062119 to demonstrate efficacy and improve patient outcomes in CRC and other gastrointestinal malignancies."

IO Biomarker • Journal • BRAF • KRAS