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A Study of SOT101 in Combination With Cetuximab to Evaluate the Efficacy and Safety in Patients With Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05619172
Recruitment Status : Not yet recruiting
First Posted : November 16, 2022
Last Update Posted : December 6, 2022
Sponsor:
Information provided by (Responsible Party):
SOTIO Biotech ( SOTIO Biotech AG )

Brief Summary:
The primary objective of the study is to estimate the antitumor efficacy of SOT101 in combination with cetuximab in RAS wild-type colorectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: SOT101 Drug: Cetuximab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Two safety cohorts will be implemented in a 3+3 dose escalation design. The main cohort will start only after data from safety cohorts are assessed by an internal safety committee.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-label, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of SOT101 in Combination With Cetuximab in Patients With RAS Wild-type Colorectal Cancer
Estimated Study Start Date : December 2022
Estimated Primary Completion Date : November 2025
Estimated Study Completion Date : November 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

Arm Intervention/treatment
Experimental: SOT101 and Cetuximab
Participants will be first treated with 9 µg/kg of SOT101 and then proceed to be treated with either 12 µg/kg or 6 µg/kg of SOT101 in combination with cetuximab (depending on the safety evaluation of the first safety cohort). SOT101 treatment will be administered on day 1 (from cycle 2 onwards, ±1 day), day 2 (±1 day), day 8 (±1 day), and day 9 (±1 day) of each 21-day cycle, Cetuximab treatment will be administered on day 1 (from cycle 2 onwards, ±1 day), day 8 (±1 day), and day 15 (±1 day) of each 21-day cycle; on day 1 and day 8, cetuximab infusion will start within 30 minutes after SOT101 administration.
Drug: SOT101
Subcutaneous (SC) injection

Drug: Cetuximab
Intravenous (IV) infusion via peripheral or central venous line




Primary Outcome Measures :
  1. Objective response rate (ORR) according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) [ Time Frame: Day 1 up to approximately 3 years ]

Secondary Outcome Measures :
  1. ORR according to RECIST for immune-based therapeutics (iRECIST) (iORR) [ Time Frame: Day 1 up to approximately 3 years ]
  2. Best overall response according to RECIST 1.1 (BOR) and iRECIST (iBOR) [ Time Frame: Day 1 up to approximately 3 years ]
  3. Duration of response according to RECIST 1.1 (DoR) and iRECIST (iDoR) [ Time Frame: Day 1 up to approximately 3 years ]
  4. Clinical benefit rate according to RECIST 1.1 (CBR) and iRECIST (iCBR) [ Time Frame: Day 1 up to approximately 3 years ]
  5. Progression-free survival (PFS) according to RECIST 1.1 and iRECIST (iPFS) [ Time Frame: Day 1 up to approximately 3 years ]
  6. Time to response according to RECIST 1.1 (TtR) and iRECIST (iTtR) [ Time Frame: Day 1 up to approximately 3 years ]
  7. Time to progression according to RECIST 1.1 (TtP) and iRECIST (iTtP) [ Time Frame: Day 1 up to approximately 3 years ]
  8. Number of participants with treatment-emergent AEs (TEAEs) [ Time Frame: Day 1 up to approximately 3 years ]
    A TEAE is defined as an AE that started or worsened at or after the start of study treatment.

  9. Number of participants with clinical laboratory test abnormalities (coagulation, hematology, clinical chemistry and urinalysis) [ Time Frame: Day 1 up to approximately 3 years ]

    The following laboratory parameters will be assessed:

    Coagulation: prothrombin time, activated partial thromboplastin time, international normalized ratio, D-dimer, and fibrinogen

    Hematology: hemoglobin, glycated hemoglobin at screening, hematocrit, red blood cell count, reticulocytes, white blood cell count (with full differentiation), absolute lymphocyte count, and platelet count

    Clinical chemistry: Na, K, Cl, phosphate, Mg, Ca, albumin, total protein, ALT, AST, bilirubin (direct, total), alkaline phosphatase, lactate dehydrogenase, creatinine clearance calculated by the Cockcroft-Gault formula, creatinine, glucose (preferably fasting), urea or blood urea nitrogen, cholesterol, triglyceride, C-reactive protein, uric acid, amylase, and lipase

    Urinalysis: pH, glucose, protein, bilirubin, urobilinogen. Microscopic examination (mandated only if clinically indicated): red blood cell count, white blood cell count, epithelial cells, bacteria


  10. Number of participants with vital signs abnormalities [ Time Frame: Day 1 up to approximately 3 years ]

    The following vital signs parameters will be assessed:

    Blood pressure (systolic and diastolic, after ≥5 minutes of rest), body temperature, and heart rate


  11. Number of participants with electrocardiography abnormalities [ Time Frame: Day 1 up to approximately 3 years ]
  12. Number of participants with DLTs [ Time Frame: Through Cycle 1 (21 days) ]

    AEs as per NCI CTCAE v5.0 considered DLTs:

    • All G5 events not clearly related to disease progression or any other causes will be considered DLTs
    • Any G3 or higher non-hematologic toxicity regardless of duration will be considered a DLT, with the following exceptions that are not considered DLTs:

      • G3 nausea, vomiting, or diarrhea that can be controlled within 72 hours
      • G3 fatigue that lasts less than 5 days
      • G3 or higher correctable electrolyte abnormalities that last less than 72 hours and are not associated with clinical complications
      • G3 or higher serum amylase or lipase not associated with clinical manifestations of pancreatitis
      • G3 AST or ALT increase or G3 blood bilirubin increase that lasts 5 days or less
    • Hy's law cases will be considered DLTs.
    • Hematologic DLTs will include the following:

      • G4 decreased neutrophil count or decreased platelet count lasting more than 7 days
      • Febrile neutropenia
      • G3 or higher decreased platelet count with bleeding

  13. Characterization of area under the curve (AUC) of SOT101 and cetuximab [ Time Frame: Day 1 of Cycle 1 until Day 1 of Cycle 3 ]
    Assessment of concentration of SOT101 and cetuximab at various timepoints

  14. Characterization of maximum concentration (Cmax) of SOT101 and cetuximab [ Time Frame: Day 1 of Cycle 1 until Day 1 of Cycle 3 ]
    Assessment of concentration of SOT101 and cetuximab at various timepoints

  15. Characterization of time to maximum concentration (Tmax) of SOT101 and cetuximab [ Time Frame: Day 1 of Cycle 1 until Day 1 of Cycle 3 ]
    Assessment of concentration of SOT101 and cetuximab at various timepoints

  16. Characterization of pre-dose concentration (Ctrough) of SOT101 and cetuximab [ Time Frame: Day 1 of Cycle 1 until Day 1 of Cycle 3 ]
    Assessment of concentration of SOT101 and cetuximab at various timepoints

  17. Characterization of terminal elimination half-life (T1/2) of SOT101 and cetuximab [ Time Frame: Day 1 of Cycle 1 until Day 1 of Cycle 3 ]
    Assessment of concentration of SOT101 and cetuximab at various timepoints

  18. Characterization of systemic clearance (CL) of SOT101 and cetuximab in single dose and steady state [ Time Frame: Day 1 of Cycle 1 until Day 1 of Cycle 3 ]
    Assessment of concentration of SOT101 and cetuximab at various timepoints

  19. Characterization of volume of distribution of SOT101 and cetuximab at steady state and during terminal phase (Vss, Vz) [ Time Frame: Day 1 of Cycle 1 until Day 1 of Cycle 3 ]
    Assessment of concentration of SOT101 and cetuximab at various timepoints

  20. Characterization of accumulation ratio (RAUC, RCmax) of SOT101 and cetuximab [ Time Frame: Day 1 of Cycle 1 until Day 1 of Cycle 3 ]
    Assessment of concentration of SOT101 and cetuximab at various timepoints

  21. Incidence of anti-drug antibodies (ADAs) against SOT101 [ Time Frame: Day 1 until 30 (±2) days after the last dose of SOT101 ]
    Measured by occurrence in time

  22. Titer of ADAs against SOT101 [ Time Frame: Day 1 until 30 (±2) days after the last dose of SOT101 ]
    Measured as lowest reactive dilution

  23. Time course of ADAs against SOT101 [ Time Frame: Day 1 until 30 (±2) days after the last dose of SOT101 ]
    Development in time

  24. Incidence of ADAs against cetuximab [ Time Frame: Day 1 until 30 (±2) days after the last dose of cetuximab ]
    Measured by occurrence in time

  25. Titer of ADAs against cetuximab [ Time Frame: Day 1 until 30 (±2) days after the last dose of cetuximab ]
    Measured as lowest reactive dilution

  26. Time course of ADAs against cetuximab [ Time Frame: Day 1 until 30 (±2) days after the last dose of cetuximab ]
    Development in time



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Type of patients

  1. ≥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 Disease characteristics
  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. EGFR mutation status should be available from a tumor biopsy taken within 3 months prior to the first administration of study treatment
  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) Organ function Have adequate organ function as defined below. Specimens must be collected within 7 days prior to the start of study treatment.
  11. Hematology:

    11.1. Absolute neutrophil count ≥1,500/µL 11.2. Platelets ≥100,000/µL 11.3. 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 <3 mg/dL). In patients with liver metastasis, ALT/AST ≤5×ULN is allowed but total bilirubin must be ≤2×ULN.
  14. Prothrombin time and activated partial thromboplastin time ≤1.5×ULN Hepatitis
  15. A locally performed hepatitis B (HBV) test is required during screening. Patients who are HBV surface antigen positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks and have undetectable HBV viral load before study entry (ICF signature). Patients should remain on anti-viral therapy throughout study treatment and follow local guidelines for HBV anti-viral therapy post completion of study treatments.
  16. A locally performed hepatitis C (HCV) test is required during screening. Patients with history of HCV infection are eligible if HCV viral load is undetectable at screening. Patients must have completed anti-viral therapy at least 4 weeks before study entry (ICF signature).

    Special requirements for contraception

  17. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and one of the following conditions applies:

    17.1. Not a woman of childbearing potential (WOCBP). A WOCBP is defined as fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single follicle stimulating hormone measurement is insufficient.

    17.2. A WOCBP who agrees to use a highly effective contraceptive method during the treatment period and for at least 60 days after the last dose of cetuximab or at least 30 days after last dose of SOT101, whichever is later.

    • WOCBP can only be included after a negative serum pregnancy test at screening within 7 days before day 1 of cycle 1.

  18. Male patients must agree to use a condom during the treatment period and for at least 60 days after the last dose of cetuximab or at least 30 days after last dose of SOT101, whichever is later.

Exclusion Criteria:

Prior/concomitant therapy

  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):

    3.1. Less than 3 weeks or 5 half lives (whichever shorter) for anti-cancer treatments 3.2. Less than 4 weeks from major surgeries and not recovered adequately from the procedure and/or any complications from the surgery

  4. 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.
  5. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatments Prior/concurrent clinical study experience
  6. 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). Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 3 weeks or 5 half lives (whichever longer) after the last dose of the previous investigational agent.

    Medical conditions

  7. Patients with known BRAF mutations
  8. Clinically significant cardiac abnormalities including prior history of any of the following:

    8.1. Cardiomyopathy, with left ventricular ejection fraction lower than the lower limit of the institutional normal range at screening 8.2. Congestive heart failure of New York Heart Association grade ≥2 8.3. 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 8.4. Prolongation of QTcF >450 msec; history or family history of congenital long QT syndrome 8.5. Uncontrolled cardiac arrhythmia requiring medication

  9. Uncontrolled hypertension defined as systolic blood pressure >160 mmHg, diastolic blood pressure >110 mmHg. Patients with uncontrolled hypertension should be medically managed on a stable regimen to control hypertension prior to study entry (ICF signature).
  10. 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. Systemic steroid pretreatment prior to cetuximab infusion according to local guidelines is permitted.
  11. History of or serology positive for HIV. A locally performed HIV test is required during screening.
  12. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Patients with basal cell carcinoma of the skin or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are eligible.
  13. Has known active central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks confirmed during screening.
  14. 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.
  15. Has an active infection requiring systemic therapy
  16. 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
  17. Has a known psychiatric or substance abuse disorder that would interfere with the patient's ability to cooperate with the requirements of the study
  18. History of hypersensitivity to any component of cetuximab or to compounds of similar biological or chemical composition of SOT101 and/or the excipients contained in the study drug formulations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05619172


Contacts
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Contact: Richard Kapsa (+420) 2241 74448 kapsa@sotio.com

Sponsors and Collaborators
SOTIO Biotech AG
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Responsible Party: SOTIO Biotech AG
ClinicalTrials.gov Identifier: NCT05619172    
Other Study ID Numbers: SC105
(AURELIO-05) ( Other Identifier: SOTIO Biotech AG )
2022-001527-32 ( EudraCT Number )
First Posted: November 16, 2022    Key Record Dates
Last Update Posted: December 6, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by SOTIO Biotech ( SOTIO Biotech AG ):
SOT101
SO-C101
Cetuximab
Colorectal cancer
AURELIO-05
Nanrilkefusp alfa
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents