RG6115 / Roche - LARVOL DELTA

Phase 1 study of RO7119929 (TLR7 agonist prodrug) in patients (pts) with advanced primary or metastatic liver cancers (AACR 2023) - P1 | "Pts received oral RO7119929 weekly in 3-week cycles in Part A (dose-escalation: Flat dosing [FD][A1], step-up dosing [SUD][A2] or FD with tocilizumab pre-treatment [A3]) and Part B (FD dose expansion with paired biopsies). SUD reduced the risk of CRS whilst maintaining mode of action relevant PD effects. Combination therapy with a checkpoint inhibitor may be needed to leverage the pro-inflammatory potential of RO7119929 and further increase anti-tumor activity."

Clinical • Metastases • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • IFNA1 • IL6

RO7119929, a TLR7 agonist prodrug, induces local inflammation of the tumor microenvironment (TME) by reprogramming myeloid cells in patients (pts) with advanced primary or metastatic liver cancers (AACR 2023) - P1 | "Single-agent TLR7 agonist treatment of advanced primary or metastatic liver cancers induces local inflammation of the TME by reprogramming myeloid cells. Combination therapies may be needed to increase the relocation of antitumor CD8 T effector cells to the TME and unlock the full potential of the local immune stimulatory effect."

Biomarker • Clinical • IO biomarker • Metastases • Tumor microenvironment • Gastrointestinal Cancer • Liver Cancer • Oncology • Solid Tumor • CD8 • PD-L1

A Study Evaluating Safety, Pharmacokinetics, Pharmacodynamics, And Clinical Activity Of RO7119929 (TLR7 Agonist) In Participants With Unresectable Advanced Or Metastatic Hepatocellular Carcinoma, Biliary Tract Cancer, Or Solid Tumors With Hepatic Metastases (clinicaltrials.gov) - P1 | N=55 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed | N=113 ➔ 55 | Trial completion date: Jun 2023 ➔ Dec 2022

Enrollment change • Metastases • Trial completion • Trial completion date • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Gallbladder Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Triple Negative Breast Cancer

A Study Evaluating Safety, Pharmacokinetics, Pharmacodynamics, And Clinical Activity Of RO7119929 (TLR7 Agonist) In Participants With Unresectable Advanced Or Metastatic Hepatocellular Carcinoma, Biliary Tract Cancer, Or Solid Tumors With Hepatic Metastases (clinicaltrials.gov) - P1 | N=113 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Gallbladder Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Triple Negative Breast Cancer

A Study Evaluating Safety, Pharmacokinetics, Pharmacodynamics, And Clinical Activity Of RO7119929 (TLR7 Agonist) In Participants With Unresectable Advanced Or Metastatic Hepatocellular Carcinoma, Biliary Tract Cancer, Or Solid Tumors With Hepatic Metastases (clinicaltrials.gov) - P1 | N=113 | Recruiting | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Recruiting | N=55 ➔ 113

Enrollment change • Enrollment open • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Gallbladder Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Triple Negative Breast Cancer

A translational strategy employing physiologically based modeling to predict the pharmacological active dose of RO7119929, an oral prodrug of a targeted cancer immunotherapy TLR7 agonist. (PubMed, Xenobiotica) - "This defined the lowest pharmacologically active dose as 3 mg.The prodrug entered the clinic in 2020 in patients with primary or secondary liver cancers. Clear pharmacodynamic, transient and dose-dependent cytokine induction was observed at prodrug doses >1 mg."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • TLR7

A Study Evaluating Safety, Pharmacokinetics, Pharmacodynamics, And Clinical Activity Of RO7119929 (TLR7 Agonist) In Participants With Unresectable Advanced Or Metastatic Hepatocellular Carcinoma, Biliary Tract Cancer, Or Solid Tumors With Hepatic Metastases (clinicaltrials.gov) - P1 | N=55 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | N=100 ➔ 55

Enrollment change • Enrollment closed • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Gallbladder Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Triple Negative Breast Cancer

A Study Evaluating Safety, Pharmacokinetics, Pharmacodynamics, And Clinical Activity Of RO7119929 (TLR7 Agonist) In Participants With Unresectable Advanced Or Metastatic Hepatocellular Carcinoma, Biliary Tract Cancer, Or Solid Tumors With Hepatic Metastases (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2022 ➔ Jun 2023

Trial completion date • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Gallbladder Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Triple Negative Breast Cancer

A Study Evaluating Safety, Pharmacokinetics, Pharmacodynamics, And Clinical Activity Of RO7119929 (TLR7 Agonist) In Participants With Unresectable Advanced Or Metastatic Hepatocellular Carcinoma, Biliary Tract Cancer, Or Solid Tumors With Hepatic Metastases (clinicaltrials.gov) - P1; N=100; Recruiting; Sponsor: Hoffmann-La Roche; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Biliary Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Gall Bladder Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Rheumatoid Arthritis • Solid Tumor • Triple Negative Breast Cancer

A Study Evaluating Safety, Pharmacokinetics, Pharmacodynamics, And Clinical Activity Of RO7119929 (TLR7 Agonist) In Participants With Unresectable Advanced Or Metastatic Hepatocellular Carcinoma, Biliary Tract Cancer, Or Solid Tumors With Hepatic Metastases (clinicaltrials.gov) - P1; N=100; Not yet recruiting; Sponsor: Hoffmann-La Roche

Clinical • New P1 trial • Biliary Cancer • Bladder Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Immunology • Inflammation • Inflammatory Arthritis • Liver Cancer • Oncology • Pancreatic Cancer • Rheumatoid Arthritis • Rheumatology • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer