Brief Summary
This is a first-in-human, Phase I, open-label, multicenter, dose-escalation and dosethe amount of medication taken expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of RO7589831 monotherapy, and in combination with pembrolizumab, in participants with microsatellite instability (MSI) and/or deficient mismatch repair (dMMR) advancedat a late stage, far along solid tumors. RO7589831 is an oral drug that acts on a protein called Werner (WRN), which may promote the growth of cancers that are MSI and/or dMMR. By acting on WRN, RO7589831 may be able to block the growth of these types of cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs.
Intervention / Treatment
- Drug: RO7589831
- Drug: Pembrolizumab
Inclusion Criteria:
- Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance status score of 0 or 1
- Have a microsatellite instability (MSI) and/or deficient mismatch repair (dMMR), histologically or cytologically documented advanced (unresectable and/or metastatic) solid tumor; for the combination with pembrolizumab only: Histologically confirmed locally advanced, or metastatic colorectalrelating to the colon or rectum in the large bowel/intestine adenocarcinomacancer arising from mucus-producing glands in organs (CRC) with no prior systemic treatment for metastatic disease and not amenable to surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence
- Have received and then progressed following, or are intolerant to, standard therapy in the advanced setting
- Presence of measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Life expectancy of at least (≥)12 weeks
- Availability of formaldehyde-fixed paraffin-embedded (FFPE) archival tumor tissuea group of cells that work together to perform a function for submission to Sponsor/central laboratory for retrospective central testing; for participants without archival tissue, a biopsyremoval of a section of tissue to analyse for cancer cells from either primary or metastatic tumor lesion, deemed medically feasible, must be taken
- Adequate hematologic, end-organ, and cardiovascular function, as defined in the protocol