ARFOLITIXORIN for Metastatic colorectal cancer

Inclusion criteria

• {"criterion_text":"- 1. Signed Informed Consent Form (ICF) and ability to comply with protocol requirements.\n- 3. Tumor specimen (formalin-fixed, paraffin-embedded [FFPE]) available.\n- 4. Acceptable hematologic laboratory values defined as: a) Hemoglobin ≥90 g/L. b) Absolute neutrophil count (ANC) ≥1.5 × 109/L. c) Platelets ≥100 × 109/L.\n- 5. Adequate organ function as defined by the following laboratory values: a) Total serum bilirubin ≤1.5 × upper limit of normal (ULN). b) Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤3 × ULN (≤5 × ULN in case of hepatic metastases). c) Creatinine ≤1.5 × ULN, or creatinine clearance ≥50 mL/min (as measured according to Cockcroft-Gault equation).\n- 12. Female patients should agree to refrain from egg cell donation while on study treatment and for at least 15 months after the last dose of study treatment.\n- 14. Male patients should agree to refrain from sperm donation while on study treatment and for at least 12 months after the last dose of study treatment.\n- 6. Age ≥18 years at the time of signing the ICF.\n- 7. Radiographically measurable disease per RECIST (version 1.1) within 28 days of treatment allocation.\n- 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n- 9. Life expectancy of >12 weeks.\n- 10. Female patients must be surgically sterile, postmenopausal (for at least 1 year), or have negative results for a pregnancy test at screening, on a serum or urine sample obtained within 72 hours prior to initiation of study treatment.\n- 11. Female patients of childbearing potential must agree to use highly effective contraceptive measures while on study treatment and for at least 15 months (or longer if according to local labels) after study treatment discontinuation. Highly effective methods are those that achieve a failure rate of less than 1% per year when used consistently and correctly (as per the Clinical Trial Coordination Group [CTCG] Recommendations related to contraception and pregnancy testing in clinical trials, Version 1.2, 07 Mar 2024)\n- 13. Male patients with female partners of childbearing potential must agree to use adequate contraceptive measures while on study treatment and for at least 12 months (or longer if according to local labels) after study treatment discontinuation.\n- 2. Phase 1b: Histologically confirmed RAS mutant, microsatellite stable (MSS)/proficient mismatch repair (pMMR), colorectal adenocarcinoma with metastatic disease, eligible for first-line therapy with 5-FU, oxaliplatin, and bevacizumab regimen. Phase 2: Histologically confirmed, colorectal adenocarcinoma with metastatic disease, eligible for first-line therapy with 5-FU based backbones, i.e.: - Patients with mutated RAS who are candidates for therapy with FOLFOX or FOLFIRI plus bevacizumab. - Patients with WT RAS or WT BRAF and left-sided tumors who are candidates for therapy with FOLFOX or FOLFIRI plus cetuximab or panitumumab."}

Exclusion criteria

• {"criterion_text":"- 1. Indication for any mCRC surgery or anti-cancer treatment other than study treatment, including but not limited to resection as confirmed by a MTB.\n- 7. Prior exposure to arfolitixorin.\n- 8. Major surgery, or significant traumatic injury within 8 weeks of study treatment initiation.\n- 9. Hypersensitivity to arfolitixorin, 5-FU, oxaliplatin or other platinum agent, irinotecan, bevacizumab, cetuximab or panitumumab, or to their excipients.\n- 10. Dihydropyrimidine dehydrogenase (DPD) enzyme deficiency test with a Clinical Pharmacogenetics Implementation Consortium (CPIC) activity score <1.\n- 4. More than 6 cycles (3 months) of oxaliplatin exposure during adjuvant treatment.\n- 15. BRAF-mutant or dMMR/MSI-H mCRC.\n- 16. Eligibility for treatment with FOLFIRINOX regimens.\n- 11. Current evidence of any condition that could lead to higher risk or otherwise make participating in this study not in the best interest of the patient, including, but not limited to: a)\tMyocardial infarction or unstable angina within the past 6 months. b)\tOther structural heart disease (e.g., myocarditis, ventricular hypertrophy). c)\tNew York Heart Association (NYHA) functional classification Class II or greater. d)\tQT prolongation syndrome >450 ms. e)\tSlow or irregular ventricular rates; other serious arrhythmias requiring medication for treatment. f)\tLeft ventricular ejection fraction (LVEF) <55%. g)\tActive infection requiring i.v. antibiotics. h)\tOngoing drug or alcohol abuse. i)\tInadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg). Initiation of antihypertensives is permitted provided adequate control is documented over at least 1 week before starting treatment.\n- 12. Sensory peripheral neuropathy Grade ≥2.\n- 13. Pregnancy or lactation.\n- 14. Any medical condition, or going treatmetn with contraindicated drugs, which in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicities, or any psychological, familial, sociological or geographical condition that potentially hampers compliance with the study protocol and follow-up schedule.\n- 2. Concomitant malignancies or previous malignancies with less than a 2-year disease-free interval at the time of signing consent. Patients with adequately treated basal or squamous cell carcinoma of the skin, or adequately treated carcinoma in situ (e.g., cervix) may enroll irrespective of the time of diagnosis. Patients with controlled, advanced prostate cancer are permitted. Ongoing adjuvant antihormonal therapy after breast or prostate cancer is permitted.\n- 3. Prior 5-FU, oxaliplatin, irinotecan, bevacizumab, cetuximab or panitumumab administration for mCRC.\n- 5. Known history of central nervous system (CNS) metastases or carcinomatous meningitis.\n- 6. Receipt of any investigational product within 14 days or 5 half-lives prior to study treatment initiation, whichever is shortest. Note that participation in any other clinical study is not allowed as long as the patient is on study treatment."}

Primary endpoints

• {"endpoint_text":"- Phase 1b: Number and severity of AEs, including clinically significant abnormal laboratory findings, regardless of causal relationship to ARFOX + bevacizumab. The outcome of Phase 1b is to determine the MTD of arfolitixorin (ARFOX + bevacizumab) in patients with mCRC.","definition_or_measurement_approach":"Number and severity of adverse events (AEs), including clinically significant abnormal laboratory findings; outcome to determine MTD based on safety/toxicity observations."}
• {"endpoint_text":"- Phase 2: ORR, defined as the proportion of patients who have BOR of CR, or PR, measured from the start of the study treatment until the EOT by RECIST (version 1.1).","definition_or_measurement_approach":"Objective response rate (ORR) = proportion with best overall response (BOR) of complete response (CR) or partial response (PR), assessed by RECIST v1.1 from treatment start until end of treatment (EOT)."}
• {"endpoint_text":"- Phase 2: Number and severity of AEs, including clinically significant abnormal laboratory findings, regardless of causal relationship to given treatment.","definition_or_measurement_approach":"Number and severity of adverse events (AEs) including clinically significant laboratory abnormalities; assessed regardless of causal relationship."}
• {"endpoint_text":"- Phase 2: DOR, defined as the duration of CR or PR.","definition_or_measurement_approach":"Duration of response (DOR) = time period that CR or PR is maintained; defined as duration of CR or PR."}

Secondary endpoints

• {"endpoint_text":"- Phase 1b: ORR, defined as the proportion of patients who have BOR of CR, or PR, measured from the start of the study treatment until the EOT by RECIST (version 1.1).","definition_or_measurement_approach":"ORR per RECIST v1.1 measured from treatment start until EOT."}
• {"endpoint_text":"- Phase 1b and Phase 2: PFS, defined as the time from date of the first study dose to the date of first documentation of confirmed disease progression or death (whichever occurs first).","definition_or_measurement_approach":"Progression-free survival (PFS) = time from first study dose to documented confirmed progression or death."}
• {"endpoint_text":"- Phase 1b and Phase 2: OS, measured from the date of study treatment initiation to the date of death.","definition_or_measurement_approach":"Overall survival (OS) = time from treatment initiation to death."}
• {"endpoint_text":"- Phase 1b: Plasma concentration of arfolitixorin.","definition_or_measurement_approach":"Pharmacokinetic measurement: plasma concentration of arfolitixorin (sampling and assay details not provided in record)."}
• {"endpoint_text":"- Phase 2: TTR, defined as the time from the first study dose date to the date of first documentation of CR or PR measured by RECIST (version 1.1).","definition_or_measurement_approach":"Time to response (TTR) = time from first dose to first documentation of CR or PR per RECIST v1.1."}
• {"endpoint_text":"- Phase 2: DCR, defined as the proportion of patients who have BOR of CR, PR, or SD ≥8 weeks.","definition_or_measurement_approach":"Disease control rate (DCR) = proportion with BOR of CR, PR, or stable disease (SD) lasting ≥8 weeks."}
• {"endpoint_text":"- Phase 2: DpR, defined as the maximum percentage change in tumor size compared with baseline.","definition_or_measurement_approach":"Depth of response (DpR) = maximum percent change in tumor size from baseline."}
• {"endpoint_text":"- Phase 2: OS, measured from the date of study treatment initiation to the date of death.","definition_or_measurement_approach":"Overall survival (OS) = time from treatment initiation to death."}
• {"endpoint_text":"- Phase 2: Proportion of patients qualifying for curative metastasis resection after treatment with study drug.","definition_or_measurement_approach":"Proportion of patients considered eligible for curative metastasis resection following study treatment (criteria and assessment details not provided)."}

Germany

Earliest CTIS Part Ii Submission Date

11-12-2024

Latest Decision Or Authorization Date

14-04-2026

Processing Time Days

489

Number Of Sites

3

Number Of Participants

90

Primary sponsor

Full Name

Isofol Medical AB (publ)

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

Link Medical GmbH

Responsibilities

Codes: 1,10,11,12,13,5,6,8

Name

LINK Medical Research AB

Responsibilities

Codes: 1,10,11,12,13,5,6,8

Name

LINK Medical Research AS

Responsibilities

Codes: 1,10,11,12,13,5,6,7,8

Name

PKxpert AB

Responsibilities

Codes: 4

Name

Viedoc Technologies AB

Responsibilities

Codes: 7

Third parties

• {"country":"Germany","full_name":"Link Medical GmbH","duties_or_roles":"Codes: 1,10,11,12,13,5,6,8","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"LINK Medical Research AB","duties_or_roles":"Codes: 1,10,11,12,13,5,6,8","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"LINK Medical Research AB (Medicon Village address)","duties_or_roles":"Codes: 1,10,11,12,13,5,6,8","organisation_type":"Industry"}
• {"country":"Sweden","full_name":"PKxpert AB","duties_or_roles":"Codes: 4","organisation_type":"Industry"}
• {"country":"Sweden","full_name":"Viedoc Technologies AB","duties_or_roles":"Codes: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Norway","full_name":"Link Medical Research AS","duties_or_roles":"Codes: 1,10,11,12,13,5,6,7,8","organisation_type":"Pharmaceutical company"}