Colorectal Cancer Metastatic
Conditions
Keywords
colorectal cancer, microsatellite stable, MSS, kras mutated, TMB-H, metastatic
Brief summary
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.
Interventions
DRUGisunakinra
Isunakinra is a potent IL1R1 inhibitor
Sponsors
Buzzard Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Subjects must have: * 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. 2\. The study patients are required to have measurable disease by radiographic criteria (RECIST 1.1 and iRECIST). 3\. 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. 4\. There should be a minimum of 4 weeks from any prior chemotherapy (except for the nitrosoureas and mitomycin C, requiring a minimum of 6 weeks), immunotherapy and/or radiation. Patients with prostate cancer on hormone deprivation therapy may continue that therapy while on study. 5\. Patients must have recovered (grade 1 or baseline) from any clinically significant toxicity associated with prior therapy (for example, alopecia is not clinically significant). 6\. ECOG performance status ≤ 1 7. Patients must have normal organ and hematologic function as defined below: * 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. * Total bilirubin ≤ 1.5 x upper limit of normal OR in patients with Gilbert's syndrome, a total bilirubin ≤ 3.0. * Hematological eligibility parameters (within 16 days of starting therapy): * Granulocyte count ≥ 1,500/mm3 * Platelet count ≥ 75.000/mm3 8. Patients must have baseline pulse oximetry \> 90% on room air at rest.
Exclusion criteria
1. Subjects must have: ⦁ 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. 2. The study patients are required to have measurable disease by radiographic criteria (RECIST 1.1 and iRECIST). 3. 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. 4. 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. 5. Patients must have recovered (grade 1 or baseline) from any clinically significant toxicity associated with prior therapy (for example, alopecia is not clinically significant). 6. ECOG performance status ≤ 1 7. Patients must have normal organ and hematologic function as defined below: * 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. * Total bilirubin ≤ 1.5 x upper limit of normal OR in patients with Gilbert's syndrome, a total bilirubin ≤ 3.0. * Hematological eligibility parameters (within 16 days of starting therapy): * Granulocyte count ≥ 1,500/mm3 * Platelet count ≥ 75.000/mm3 8. Patients must have baseline pulse oximetry \> 90% on room air at rest.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety | 6 months | The incidence, relatedness and severity of adverse events (includes safety laboratory abnormalities) per CTCAE v. 5 |
| PFS | 6 months | Progression Free Survival per iRECIST |
Countries
United States
Contacts
CONTACTMaarten de Chateau, MD PhD
CONTACTHans Olivecrona, MD PhD
Outcome results
None listed