This phase I trial tests the safety, side effects and best dose of peposertib (M3814) in combination with tuvusertib (M1774) in treating patients with solid tumors that have spread to other places in the body (advanced). Peposertib and tuvusertib stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Patients must have histologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective, or if the treating investigator deems the study appropriate.
For the dose escalation and dose expansion phases, patients must have genomic (tumor next-generation sequencing [NGS], circulating tumor deoxyribonucleic acid [ctDNA], fluorescence in situ hybridization [FISH], etc.) or immunohistochemical evidence (e.g., loss of expression) of inactivating ATM mutations, MYC amplification, mutation of FBXW7, CCNE1 amplification, SWI/SNF member mutation (ARID1A, PBRM1, SMARCA4, ARID2, ARID1b, SMARCB1, SMARCA2, SS18) and mutation or loss of expression of ATRX/DAXX. Mutations may be germline or somatic. All mutations/alterations must be approved by the overall principal investigator (PI). Other SWI/SNF mutations may be considered after discussion with the overall PI.
Progression on at least one prior standard therapy (if no standard therapy exists, the patient may be allowed if the treating investigator deems appropriate).
Age >= 18 years. Because no dosing or adverse event data are currently available on the use of peposertib (M3814) in combination with tuvusertib (M1774) in patients < 18 years of age, children are excluded from this study.
Patients who have received immunotherapy within 21 days of Cycle 1 Day 1.
Patients who have received therapeutic radiation therapy within 21 days, or palliative radiation therapy within 7 days, of Cycle 1 Day 1.
Patients who have undergone major surgery within 21 days of Cycle 1 Day 1.
Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia, controlled endocrine toxicity (e.g., hypothyroidism), and cutaneous toxicity which will be permitted at Grade 2.