GO45416 - A phase I/II dose escalation and expansion study evaluating the safety, pharmacokinetics, and activity of GDC-7035 as a single agent and in combination with other anti-cancer therapies in patients with advanced solid tumours with a KRAS G12D mutation

This study is testing an experimental drug called GDC-7035 (also called RO7782493) in patients with advanced or metastatic solid tumours that have the KRAS G12D mutation. Advanced’ or ‘metastatic’ means that the cancer has spread to other areas of the body. The specific KRAS G12D mutation is prevalent in colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), nonsmall cell lung cancer (NSCLC) and other tumour types. Although current treatment options for CRC, PDAC, NSCLC, and other solid tumours continue to improve outcomes for patients, these diseases remain incurable with limited survival times. GDC-7035 (RO7782493) is an oral anti-cancer experimental drug that selectively holds back KRAS G12D. Nonclinical studies show that treatment of KRAS G12D positive cancer cell lines with GDC-7035 results in suppressed cell growth. This is a first in-human trial that will investigate the safety and activity of GDC-7035 on its own and in combination with other anti-cancer therapies when given to patients with KRAS G12D positive solid tumours. The study consists of a screening period of up to 28 days, a treatment period of up to 12 months and a safety follow-up period of 28 days. There will be two stages in the study: a dose-escalation stage to determine maximum tolerated dose (MTD) or maximum administered dose (MAD) for GDC-7035 and GDC-7035 in combination with other anti-cancer therapies and an expansion stage to obtain further data in specific disease areas. Approximately 410 eligible patients are expected to take part in this study globally. The study will involve assessments including vitals, physical exams, blood and urine testing, questionnaire completion, ECG, biopsy and imaging for tumour assessment.