RAS wild-type colorectal cancer
Conditions
Interventions
Product Name: SOT101
Product Code: SOT101, SO-C101, RLI-15
Pharmaceutical Form: Solution for injection
INN or Proposed INN: nanrilkefusp alfa
CAS Number: 1416390-27-6
Current Sponsor code: SOT101
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Sponsors
SOTIO Biotech AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. > or =18 years of age on the day of signing informed consent 2. Ability to understand and sign written informed consent to participate in the study 3. Provides written informed consent for the study 4. Life expectancy >6 months 5. Histologically or cytologically confirmed advanced and/or metastatic RAS wild-type colorectal cancer as confirmed by the investigational site within 3 months prior to the first administration of study treatment. For the assessment of the RAS mutational status, a US Food and Drug Administration (FDA)-approved test or an experienced local laboratory using validated test methods for the detection of K-RAS and N-RAS (exons 2, 3, and 4) mutations must be used. 6.RAS wild type as confirmed by: • locally performed US Food and Drug Administration (FDA)-approved test or an experienced local laboratory using validated test methods for the detection, based on tumor biopsy or • locally performed ctDNA assessment including at least mutations in exon 2 (G12D, G12V, G12C, G12S, G12A, G12R, G13D) and determined by a laboratory using validated test methods • samples must be taken within 3 months prior to first study administration. 7. Patients who are relapsed/refractory or intolerant to prior treatment with irinotecan- and oxaliplatin-containing chemotherapy 8. Have at least one measurable lesion according to RECIST 1.1 9. Eastern Cooperative Oncology Group (ECOG) performance score 0-2 10. Must have recovered from all AEs due to previous therapies to grade =1 toxicity (excluding alopecia) 11. Hematology: - Absolute neutrophil count =1,500/µL - Platelets =100,000/µL - Hemoglobin =9.0 g/dL (criteria must be met without packed red blood cell transfusion within the prior 2 weeks; patients can be on stable dose of erythropoietin [=3 months]) 12. Renal function: Creatinine clearance rate =50 mL/min as calculated using Cockcroft-Gault equation 13. Hepatic function: ALT/AST =2.5× upper limit of normal (ULN) and total bilirubin =2×ULN in patients without liver metastasis (benign hereditary hyperbilirubinemias,e.g., Gilbert’s syndrome, are permitted if total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: 1. Prior exposure to drugs that are agonists of IL-2 or IL-15 2. Therapy with cetuximab within 3 months prior to ICF signature or patients who had progressive disease as best response to prior cetuximab-containing regimen 3. Prior systemic anti-cancer therapies, including investigational agents before study entry (ICF signature). 4. Has received more than 4 prior lines of systemic anticancer treatment 5. Has received prior radiotherapy within 2 weeks of the start of study treatments. A 1-week radiation-free period is permitted for palliative radiation (=2 weeks of radiotherapy) to non-central nervous system disease. Patients must have recovered from all radiation-related toxicities and not require corticosteroids. 6. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatments 7. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 3 weeks or 5 half-lives (whichever longer) before study entry (ICF signature). 8. Patients with known BRAF mutations 9. Clinically significant cardiac abnormalities including prior history of any of the following: -Cardiomyopathy, with left ventricular ejection fraction lower than the lower limit of the institutional normal range at screening - Congestive heart failure of New York Heart Association grade =2 - History of clinically significant (i.e., active) atherosclerotic cardiovascular disease, specifically myocardial infarction, unstable angina, cerebrovascular accident within 6 months prior to the first dose of study treatments, and any history of coronary heart disease and clinically significant peripheral and/or carotid artery disease -Prolongation of QTcF >450 msec; history or family history of congenital long QT syndrome -Uncontrolled cardiac arrhythmia requiring medication 10. Uncontrolled hypertension defined as systolic blood pressure >160 mmHg, diastolic blood pressure >110 mmHg. 11. Has a clinical diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatments. 12. History of or serology positive for HIV. A locally performed HIV test is required during screening. 13. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. 14. Has known active central nervous system metastases and/or carcinomatous meningitis. 15. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 16. Has an active infection requiring systemic therapy 17. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient’s participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator 18. Has a known psychiatric or substance abuse disorder that would interfere with the patient’s ability to cooperate with the requirements of the study 19. History of hypersensitivity t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the antitumor efficacy of nanrilkefusp alfa in combination with cetuximab;Secondary Objective: - To further evaluate the antitumor efficacy of nanrilkefusp alfa in combination with cetuximab - To assess the safety and tolerability of nanrilkefusp alfa in combination with cetuximab - To determine the RP2D of nanrilkefusp alfa in combination with cetuximab - To characterize the pharmacokinetics (PK) of nanrilkefusp alfa and cetuximab in a subset of patients - To determine the immunogenicity of nanrilkefusp alfa in combination with cetuximab - To determine the immunogenicity of cetuximab in combination with nanrilkefusp alfa ;Primary end point(s): - Objective response rate (ORR) according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1);Timepoint(s) of evaluation of this end point: RECIST 1.1 will be used as the primary measure for assessment of tumor response, date of disease progression, and as a basis for all protocol guidelines related to disease status (e.g., discontinuation of study interventions). according to schedule of activities this is at the follow up phase | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ORR according to RECIST for immune-based therapeutics (iRECIST)20 (iORR) • Best overall response according to RECIST 1.1 (BOR) and iRECIST (iBOR) • Duration of response according to RECIST 1.1 (DoR) and iRECIST (iDoR) • Clinical benefit rate according to RECIST 1.1 (CBR) and iRECIST (iCBR) • Progression-free survival (PFS) according to RECIST 1.1 and iRECIST (iPFS) • Time to response according to RECIST 1.1 (TtR) and iRECIST (iTtR) • Time to progression according to RECIST 1.1 (TtP) and iRECIST (iTtP) Type, frequency, and severity of treatment-emergent AEs (TEAEs) according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0; safety laboratory findings; vital signs; electrocardiography findings • Dose-limiting toxicities (DLTs) • Serum concentrations and calculated PK parameters of SOT101 and cetuximab • Incidence, titer, and time course of anti-drug antibodies (ADAs) against SOT101 • Incidence, titer, and time course of ADAs against cetuximab •;Timepoint(s) of evaluation of this end point: according to RECIST 1.1 and iRECIST | — |
Countries
Belgium, Italy, Spain
Contacts
Public ContactClinical Trial SOTIO
SOTIO Biotech a.s.
Outcome results
None listed