PF-07284892 / Pfizer - LARVOL DELTA

A first-in-human, phase 1 study of the SHP2 inhibitor PF-07284892 as monotherapy and in combination with different targeted therapies in oncogene-driven, treatment-resistant solid tumors. (ASCO 2023) - P1 | "In the absence of dose limiting toxicity (DLT), matched targeted therapy (lorlatinib for ALK/ROS1 fusion+ cancers, encorafenib + cetuximab for BRAFV600E colorectal cancers, and binimetinib for MAPK-mutant cancers) could be added after 6 weeks of monotherapy at the discretion of the investigator. PF-07284892 was generally well tolerated alone and in combination with rational targeted therapies. This study design enabled combination therapy rescue of disease progression on PF-07284892 monotherapy with 3 pts achieving confirmed PR. Clinical trial information: NCT04800822."

Combination therapy • Monotherapy • P1 data • Anemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Disorders • Oncology • Solid Tumor • Thrombocytopenia • ALK • ROS1

A Study to Learn About the Study Medicine PF-07985045 When Given Alone or With Other Anti-cancer Therapies in People With Advanced Solid Tumors That Have a Change in a Gene. (clinicaltrials.gov) - P1 | N=30 | Terminated | Sponsor: Pfizer | Not yet recruiting ➔ Terminated; The trial was terminated for strategic business reasons; the decision was not based on any safety and/or efficacy concerns.

IO biomarker • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • KRAS • ROS1

A Study to Learn About the Study Medicine PF-07985045 When Given Alone or With Other Anti-cancer Therapies in People With Advanced Solid Tumors That Have a Change in a Gene. (clinicaltrials.gov) - P1 | N=30 | Terminated | Sponsor: Pfizer | Trial completion date: Mar 2029 ➔ May 2026 | Active, not recruiting ➔ Terminated | Trial primary completion date: Mar 2028 ➔ May 2026; The trial was terminated for strategic business reasons; the decision was not based on any safety and/or efficacy concerns.

IO biomarker • Trial completion date • Trial primary completion date • Trial termination • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • ALK • KRAS • ROS1

A Study to Learn About the Study Medicine PF-07985045 When Given Alone or With Other Anti-cancer Therapies in People With Advanced Solid Tumors That Have a Change in a Gene. (clinicaltrials.gov) - P1 | N=26 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=190 ➔ 26

Enrollment change • Enrollment closed • IO biomarker • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • ALK • KRAS • ROS1

A Study to Learn About the Study Medicine PF-07985045 When Given Alone or With Other Anti-cancer Therapies in People With Advanced Solid Tumors That Have a Change in a Gene (clinicaltrials.gov) - P1 | N=190 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open • IO biomarker • Colorectal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

A Study to Learn About the Study Medicine PF-07985045 When Given Alone or With Other Anti-cancer Therapies in People With Advanced Solid Tumors That Have a Change in a Gene (clinicaltrials.gov) - P1 | N=190 | Not yet recruiting | Sponsor: Pfizer

Combination therapy • IO biomarker • Metastases • New P1 trial • Colorectal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

PF-07284892 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=53 | Terminated | Sponsor: Pfizer | Trial completion date: Nov 2025 ➔ Jun 2024 | Active, not recruiting ➔ Terminated; The study was prematurely discontinued due to strategic reasons, not major safety concerns, futility, or requests from any regulatory authorities

Combination therapy • Metastases • Trial completion date • Trial termination • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • NF1 • ROS1

PF-07284892 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=53 | Active, not recruiting | Sponsor: Pfizer | N=36 ➔ 53

Combination therapy • Enrollment change • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • NF1 • ROS1

PF-07284892 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=196 ➔ 36

Enrollment change • Enrollment closed • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • NF1 • ROS1

Pfizer SHP2 Inhibitor Shows Early Efficacy Across Resistant Tumors in Combination Regimens (Precision Medicine Online) - P1 | N= 196 | NCT04800822 | Sponsor: Pfizer | "The cancer types represented in the study included EML4-ALK fusion-positive non-small cell lung cancer, BRAF V600E-mutant colorectal cancer, KRAS G12D-mutant low-grade serous ovarian cancer, and GOPC-ROS1 fusion-positive pancreatic cancer...In the study, the first four patients to progress from PF-07284892 to personalized combination regimens achieved a partial response on the latter. In fact, in the combination portion of the study, two of these patients received the same targeted therapy that they had progressed on and were resistant to earlier. However, when combined with PF-07284892, they responded to these drugs...None of the four patients experienced dose-limiting toxicities on these PF-07284892-containing combinations, though two patients..."

P1 data • Colorectal Cancer • Ovarian Cancer • Pancreatic Cancer

Pfizer SHP2 Inhibitor Shows Early Efficacy Across Resistant Tumors in Combination Regimens (Precision Medicine Online) - "While Pfizer's Phase I trial of PF-07284892 is still in early stages, the firm is already looking ahead to larger studies. Next, researchers are planning trials where they'll study PF-07284892 combination regimens from the beginning 'in appropriate biomarker-selected patients, for whom concomitant inhibition with a SHP2 inhibitor may overcome or delay relevant resistance mechanisms or pathways'...Pfizer plans to continue exploring PF-07284892 in the tumor types included in the Phase I study – lung, colorectal, ovarian, and pancreatic – and may expand into others if data suggests adding a SHP2 inhibitor may provide clinical benefit."

New trial • Colorectal Cancer • Lung Cancer • Ovarian Cancer • Pancreatic Cancer

PF-07284892 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=196 | Recruiting | Sponsor: Pfizer | Trial completion date: Sep 2026 ➔ Dec 2025 | Trial primary completion date: Jun 2025 ➔ Jun 2024

Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • NF1 • ROS1

SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy. (PubMed, Cancer Discov) - "PF-07284892 (ARRY-558) is an allosteric SHP2 inhibitor designed to overcome bypass-signaling-mediated resistance when combined with inhibitors of various oncogenic drivers...This provides proof of concept of the utility of SHP2 inhibitors in overcoming resistance to diverse targeted therapies and provides a paradigm for accelerated testing of novel drug combinations early in clinical development. See related commentary by Hernando-Calvo and Garralda."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • ALK • KRAS • ROS1

Patient Centric Approaches for Phase I Combination Trials Come on Stage. (PubMed, Cancer Discov) - "A disruptive clinical trial design allowed Drilon and colleagues to demonstrate proof of concept of the potential of PF-07284892 to overcome resistance mechanisms to targeted therapies in the clinic. See related article by Drilon et al. (7)."

Journal • P1 data

PF-07284892 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=196 | Recruiting | Sponsor: Pfizer | Trial completion date: Apr 2026 ➔ Sep 2026

Trial completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • NF1 • ROS1

PF-07284892 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=196 | Recruiting | Sponsor: Pfizer | Trial completion date: Feb 2027 ➔ Apr 2026 | Trial primary completion date: Feb 2026 ➔ Apr 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • NF1 • ROS1

PF-07284892 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=211; Recruiting; Sponsor: Pfizer; N=70 ➔ 211

Clinical • Combination therapy • Enrollment change • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • NF1

PF-07284892 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=70; Recruiting; Sponsor: Pfizer; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • NF1

PF-07284892 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=70; Not yet recruiting; Sponsor: Pfizer

Clinical • Combination therapy • New P1 trial • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • NF1