M6620 and Irinotecan Hydrochloride in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

Inclusion Criteria: * Patients must have histologically confirmed metastatic or unresectable malignancy that is refractory to standard therapy or for which no standard therapy exists and where irinotecan is deemed a reasonable treatment option * FOR PATIENTS ENROLLED IN THE EXPANSION COHORT: Patients must have known deficiencies in the deoxyribonucleic acid (DNA)-Damage Response (DDR), e.g. mutations in ATM, PALB2, BRCA1/2 or other deficiencies after discussion with the Study Chair (prioritized), or patients can be enrolled with the following tumor types regardless of known DDR deficiency: pancreatic cancer, colorectal cancer, and small cell lung cancer * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) with conventional techniques or as \>= 10 mm (\>= 1 cm) with spiral CT scan, magnetic resonance imaging (MRI), or calipers by clinical exam * No limit on prior lines of therapy for metastatic disease; prior adjuvant or neoadjuvant chemotherapy does not count as a prior line of therapy as long as completion of the adjuvant or neoadjuvant therapy was more than 1 year prior to patient enrollment * Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of M6620 (VX-970, berzosertib) in combination with irinotecan in patients \< 18 years of age, children …