This study will enroll patients with colorectal cancer that is locally advanced or metastatic. The tumor must be microsatellite stable (MSS), have a tumor mutational burden that is high (TMB-H) and be kras mutated. Patients must have been treated with available approved treatments already. In this study the investigators are testing a new type of immunotherapy, the potent IL-1 inhibitor isunakinra to be added to already approved immunotherapy (PD-1/PD-L1 inhibitor) in an attempt to get this treatment to work in this treatment resistant type of tumor.
Histologically or cytologically confirmed adenocarcinoma of the colon or the rectum
Tumor is determined to be RAS-mutated (KRAS, NRAS or HRAS) and microsatellite stable/proficient in mismatch repair, as assessed by immunohistochemistry (IHC) and/or polymerase chain reaction (PCR)/next generation sequencing (NGS) in a Clinical Laboratory Improvement Act (CLIA) environment and with a tumor mutational burden (TMB) of 10 MB or more.
Serum creatinine ≤ 1.5 x upper limit of normal OR creatinine clearance and a 24-h urine collection of ≥ 60 mL/min.
ALT and AST ≤ 3x the upper limits of normal.
The study patients are required to have measurable disease by radiographic criteria (RECIST 1.1 and iRECIST).
Prior therapy: Patients must have completed or had disease progression on at least one prior line of disease-appropriate therapy for metastatic disease (with or without PD-1 inhibitors), with no available therapy likely to convey clinical benefit, or not be candidates for therapy of proven efficacy for their disease.
There should be a minimum of 2 weeks wash out period from chemotherapy and/or radiation therapy, and 4 weeks wash out period for immunotherapy.
Patients must have recovered (grade 1 or baseline) from any clinically significant toxicity associated with prior therapy (for example, alopecia is not clinically significant).