A Study to Assess Safety and Efficacy of SOT109 in Patients With Advanced Unresectable or Metastatic Colorectal Cancer

A First-in-human Phase 1/2 Trial to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of SOT109 in Patients With Advanced Unresectable or Metastatic Colorectal Cancer

SOT109 is a special cancer medicine designed to find and kill certain cancer cells that carry a marker called CDH17, while causing less harm to healthy cells. The study consists of two parts, Part A and Part B. The goal of Part A is to collect information about SOT109, understand its effects, and see whether it is safe and well tolerated at different dose levels. Part B of the study collects information on which of the two selected safe dose levels chosen in Part A gives the best balance between benefit and risk.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer (Locally Advanced or Metastatic)
• Intervention / Treatment: Biological: SOT109

Detailed Description

The trial will consist of the following parts:

• Part A: a multinational, multicenter, open-label, TITE-BOIN-guided trial to determine the MTD and RP2Ds, to evaluate the safety, PK, and preliminary efficacy of escalating doses of SOT109 in participants with advanced unresectable or metastatic colorectal cancer who have received and/or have been determined to be intolerant of all standard of care therapy known to confer clinical benefit.
• Part B: This is a randomized, multinational, multicenter, open-label dose optimization trial evaluating the two recommended doses for optimization (RDOs) identified in Part A. After the determination of the MTD in Part A and identification of RDOs, a randomized dose optimization part will be initiated to evaluate the two selected RDOs and to identify the optimal biological dose that offers the best balance between benefit and risk and to evaluate safety and efficacy of SOT109 in participants with advanced unresectable or metastatic colorectal cancer who have no further standard treatment options.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Richard Kapsa; Phone Number: (+420) 2241 74448; Email: kapsa@sotio.com

Study Locations

• Moldova
  • Chisinau, Moldova
    • Arensia Exploratory Medicine Research Unit, Institute of Oncology
    • Contact: Arensia Exploratory Medicine Research Unit, Institute of Oncol; Phone Number: +373 68541058
• United States
  • Texas
    • Houston, Texas, United States, 77054
      • NEXT Houston
      • Contact: NEXT Houston; Phone Number: 210 580-9500
  • Virginia
    • Faifax, Virginia, United States, 22031
      • NEXT Virginia
      • Contact: NEXT Virginia, 703 783 4510

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ≥18 years of age on the day of signing the ICF
2. Able to understand, sign, and provide written informed consent to participate in the trial
3. Performance status: Eastern Cooperative Oncology Group (ECOG) performance score 0-1. Patients with ECOG performance score 2 will be discussed with the sponsor's medical monitor to be agreed for inclusion
4. Estimated life expectancy ≥3 months as assessed by the investigator
5. An appropriate candidate for experimental therapy as assessed by the investigator
6. Agrees not to participate in other interventional clinical trial while enrolled in the present trial (with the exception of survival follow-up period)
7. Absolute neutrophil count ≥1.5×109/L, platelets ≥100×109/L, hemoglobin ≥9 g/dL
8. Creatinine clearance ≥60 mL/min calculated by Cockcroft-Gault formula

9. Bilirubin ≤1.5× upper limits of normal (ULN), ALT and AST ≤2.5×ULN; in case of liver involvement: AST and ALT ≤5×ULN

   • Participants with a documented history of Gilbert syndrome may be eligible if:

   • Total bilirubin is ≤2.0 × ULN,
   • Direct (conjugated) bilirubin is within normal limits (≤ULN), and
   • There is no evidence of active liver disease, clinically significant hepatic impairment, hemolysis, or biliary obstruction, as determined by the investigator
10. Prothrombin time/international normalized ratio ≤1.5×ULN
11. Albumin ≥3.0 mg/dL
12. Serum concentrations of potassium, magnesium, and calcium with abnormalities of maximum grade 1 that should be treated according to standard practice
13. Left ventricular ejection fraction (LVEF) ≥50% as determined by echocardiography or nuclear medicine methodology (MUGA)
14. QTcF interval ≤470 msec on screening ECG
15. Histological or cytological evidence of advanced unresectable or metastatic colorectal cancer
16. Participants that received and progressed on standard systemic therapies (fluoropyrimidines, oxaliplatin, irinotecan, bevacizumab, and, only when locally indicated and available, a BRAF/RAS/HER2 inhibitor) and who have no further standard treatment options. Participants with a known microsatellite instability-high (MSI-H) status must have received treatment with an immune checkpoint inhibitor (if locally indicated and available) unless contraindicated
17. Measurable or non-measurable disease according to RECIST 1.1

18. Previous cancer therapies:

    18.1. Europe: previous cancer therapies and any agents that have not received regulatory approval for any indication must have been discontinued either ≥21 days prior to day 1 of cycle 1 or ≥5x half-life, whichever is longer; toxicities of earlier anticancer therapy must be grade ≤1 at the time of screening and prior to cycle 1 day 1 (exception: alopecia) 18.2. US: eligibility should be determined based on patient recovery from clinically significant adverse events from their most recent therapy or intervention prior to study enrollment

19. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and one of the following conditions applies: 19.1. Not a woman of childbearing potential (WOCBP). A WOCBP is defined as fertile, following menarche, and until becoming postmenopausal 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 postmenopausal 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.

    19.2. A WOCBP who agrees to use a highly effective contraceptive method during the treatment period and for at least 6 months after the last dose of SOT109

    • WOCBP can only be included after a negative serum pregnancy test at screening

    • Highly effective contraception includes:

      • Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation:

        • Oral
        • Intravaginal
        • Transdermal

      • Progestogen-only hormonal contraception associated with inhibition of ovulation:

        • Oral
        • Injectable
        • Implantable
      • Intrauterine device
      • Intrauterine hormone-releasing system
      • Bilateral tubal occlusion
      • Vasectomized partner provided the partner is the sole sexual partner of the WOCBP participant and that the vasectomized partner has received medical assessment of the surgical success
      • Sexual abstinence defined as refraining from heterosexual intercourse during the entire treatment period and for at least 6 months after the last dose of SOT109. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant.
20. Male participants must agree to use a condom during the treatment period and for at least 6 months after the last dose of SOT109. Male participants wishing to become a father during or after the trial should consider sperm preservation. WOCBP partners of male participants should use highly effective contraception methods for 6 months after SOT109 discontinuation.

Exclusion Criteria:

1. Received radiation therapy ≤14 days before day 1 of cycle 1 or not recovered to grade ≤1 from treatment-related side effects

2. Any prior systemic therapy for metastatic cancer other than colorectal cancer; exception:

   stable disease under hormonal treatment for prostate cancer, stable disease under hormonal treatment for breast cancer; radiochemotherapy is allowed if such treatment is completed at least 4 weeks prior to day 1 of cycle 1; participants must have recovered to grade ≤1 from all side effects (exception: alopecia)

3. Participants must not receive any concurrent antitumor therapy while participating in the trial. In exceptional circumstances where urgent palliative radiotherapy to symptomatic non-target lesions is clinically indicated, the case must be reviewed with the Principal Investigator (PI) and the intervention must receive prior approval from the sponsor
4. Vaccination with a live or live-attenuated vaccine within 30 days prior to the first dose of trial interventions; the full series (e.g., both doses of a two dose vaccination series) should be completed prior to dosing if feasible
5. Time since last transfusion of red blood cells ≤14 days before day 1 of cycle 1
6. Severe preexisting medical conditions as per judgment of the investigator
7. History of interstitial pneumonitis or pulmonary fibrosis
8. Symptomatic central nervous system malignancy. Participants with asymptomatic or treated central nervous system metastases may be eligible if they are not treated with corticosteroids or anticonvulsants and the disease is stable for at least 60 days
9. Peripheral sensory neuropathy grade ≥2
10. Active infection requiring systemic therapy that is not clinically controlled before the signature of the ICF
11. Known symptomatic HIV positive, symptomatic active HBV, or symptomatic active HCV

Note:

• Participants with HIV will be eligible if:

  • CD4+ T-cell counts ≥350 cells/μL
  • They have no history of AIDS-defining opportunistic infections
  • They are not currently on HIV therapy
• Participants with HBV will be eligible if there is serologic evidence of a resolved prior HBV infection (HBsAg-negative and HBcAb-positive)
• Participants with HCV will be eligible if they have completed curative antiviral treatment and have HCV viral load below the limit of quantification 12. Alcohol or drug abuse as determined by the investigator 13. Psychiatric condition or social situation that, in the opinion of the investigator, preclude that the participant is able to comply with trial requirements 14. New York Heart Association class ≥2 heart failure, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, myocardial infarction, cerebrovascular accident or hypertensive crisis within 6 months prior to day 1 of cycle 1 15. History of major ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, Torsades de Pointes) 16. History or family history of congenital long QT syndrome 17. Bradycardia (<50 beats per minute) 18. Family history of sudden cardiac death before age 50 19. Major surgical intervention ≤28 days prior to ICF signature or incomplete wound healing after surgical intervention 20. Hypersensitivity or intolerance to any component of trial intervention 21. Medical history of inflammatory bowel disease or active inflammatory bowel disease (IBD)
• Participants with signs or symptoms suggestive of IBD who have not undergone colonoscopy to rule out IBD will be excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SOT109 (Part A) dose level 1; Patients with advanced unresectable or metastatic colorectal cancer treated with SOT109 given once every 21 days via the IV route over 30 (±15) minutes.	Biological: SOT109; SOT109 is a CDH17-directed monoclonal antibody conjugated to a linker-payload, exatecan
Experimental: SOT109 (Part A) dose level 2; Patients with advanced unresectable or metastatic colorectal cancer treated with SOT109 given once every 21 days via the IV route over 30 (±15) minutes.	Biological: SOT109; SOT109 is a CDH17-directed monoclonal antibody conjugated to a linker-payload, exatecan
Experimental: SOT109 (Part A) dose level 3; Patients with advanced unresectable or metastatic colorectal cancer treated with SOT109 given once every 21 days via the IV route over 30 (±15) minutes.	Biological: SOT109; SOT109 is a CDH17-directed monoclonal antibody conjugated to a linker-payload, exatecan
Experimental: SOT109 (Part A) dose level 4; Patients with advanced unresectable or metastatic colorectal cancer treated with SOT109 given once every 21 days via the IV route over 30 (±15) minutes.	Biological: SOT109; SOT109 is a CDH17-directed monoclonal antibody conjugated to a linker-payload, exatecan
Experimental: SOT109 (Part A) dose level 5; Patients with advanced unresectable or metastatic colorectal cancer treated with SOT109 given once every 21 days via the IV route over 30 (±15) minutes.	Biological: SOT109; SOT109 is a CDH17-directed monoclonal antibody conjugated to a linker-payload, exatecan
Experimental: SOT109 (Part B) recommended dose for optimization 1; Patients with advanced unresectable or metastatic colorectal cancer treated with SOT109 given once every 21 days via the IV route over 30 (±15) minutes.	Biological: SOT109; SOT109 is a CDH17-directed monoclonal antibody conjugated to a linker-payload, exatecan
Experimental: SOT109 (Part B) recommended dose for optimization 2; Patients with advanced unresectable or metastatic colorectal cancer treated with SOT109 given once every 21 days via the IV route over 30 (±15) minutes.	Biological: SOT109; SOT109 is a CDH17-directed monoclonal antibody conjugated to a linker-payload, exatecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of SOT109	MTD will be selected as guided by the time to-event Bayesian optimal interval (TITEBOIN) design. The RP2D will be selected based on integrated evaluation of the totality of clinical and preclinical data, for all dose levels tested.	At the end of Cycle 1 (one cycle is 21 days)
Part B: Optimal dose of SOT109 for subsequent clinical trials	Assessment of the safety and tolerability of two recommended doses under evaluation for dose optimization (RDOs) of SOT109 by evaluation of the occurrence of SOT109 related TEAEs, serious TEAEs, TEAEs leading to premature discontinuation of SOT109, deaths, and clinical laboratory test abnormalities of grade 3 or higher according to NCI CTCAE Version 6.0	Cycle 1 Day 1 up to 30 days after the last dose (each cycle is 21 days)
Part B: Objective Response Rate (ORR) of SOT109	Percentage of participants who achieve a Best Overall Response of Complete Response (CR) or Partial Response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	From Day 1 of Cycle 1 (one cycle is 21 days) until disease progression, initiation of new anticancer therapy, withdrawal of consent, or study discontinuation, whichever comes first, to be assessed up to approximately 9 months
Part B: Duration of Response (DoR) of SOT109	The time from the first documentation of objective response (CR or PR) to the first documented date of progressive disease (PD) according to RECIST v1.1.	From the date of first documented objective response until disease progression, initiation of new anticancer therapy, withdrawal of consent, or study discontinuation, whichever comes first, assessed up to approximately 9 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Safety and Tolerability of SOT109	The occurrence of dose-limiting toxicities (DLTs), SOT109-related treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs leading to premature discontinuation of SOT109, deaths, and clinical laboratory test abnormalities of grade 3 or higher according to National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) Version 6.0	From Cycle 1 Day 1 (one cycle is 21 days) assessed for approximately 12 months
Part A: Characterization of maximum concentration (Cmax)	Cmax in plasma of total antibody, conjugated antibody and free exatecan.	From Cycle 1 Day 1 up to approximately 12 months (each cycle is 21 days)
Part A: Characterization of time to maximum concentration (Tmax)	Time to maximum concentration of total antibody, conjugated antibody and free exatecan.	From Cycle 1 Day 1 up to approximately 12 months (each cycle is 21 days)
Part A: Characterization of area under the curve	Area under the concentration versus time curve calculated for total antibody, conjugated antibody and free exatecan.	From Cycle 1 Day 1 up to approximately 12 months (each cycle is 21 days)
Part A: Preliminary anticancer activity of SOT109	Tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by CDH17 expression	From Day 1 of Cycle 1 (one cycle is 21 days) until disease progression, initiation of new anticancer therapy, withdrawal of consent, or study discontinuation, whichever comes first, to be assessed up to approximately 12 months
Part A: Immunogenicity of SOT109 as Evaluated by Anti-Drug Antibody (ADA) Incidence	Proportion of participants who test positive for ADAs to SOT109.	From Cycle 1 Day 1 up to approximately 12 months (each cycle is 21 days)
Part B: Progression-Free Survival (PFS) of SOT109	Progression-free survival is defined as the time from Cycle 1 Day 1 to the first documented date of progressive disease (PD) according to RECIST v1.1, or death from any cause, whichever occurs first	From Cycle 1 Day 1 (one cycle is 21 days) until first documented disease progression or death from any cause, assessed up to approximately 9 months
Part B: Characterization of Cmax	Evaluation of the maximum plasma concentration (Cmax) for total antibody, conjugated antibody, and free exatecan payload.	From Cycle 1 Day 1 up to approximately 9 months (each cycle is 21 days)
Part B: Characterization of Tmax	Evaluation of the time to maximum plasma concentration (Tmax) for total antibody, conjugated antibody, and free payload.	From Cycle 1 Day 1 up to approximately 9 months (each cycle is 21 days)
Part B: Characterization of area under the curve	To characterize the total drug exposure over time (AUC) for total antibody, conjugated antibody, and free payload.	From Cycle 1 Day 1 up to approximately 9 months (each cycle is 21 days)
Part B: Immunogenicity of SOT109 as Evaluated by Anti-Drug Antibody (ADA) Incidence	Proportion of participants who test positive for ADAs to SOT109. The potential impact of ADA status on the pharmacokinetic (PK) profiles (Cmax, AUC, Tmax) of SOT109 will be evaluated by comparing PK data between ADA-positive and ADA-negative participants	From Cycle 1 Day 1 up to approximately 9 months (each cycle is 21 days)

Collaborators and Investigators

• Sponsor: SOTIO Biotech a.s.
• Investigators: Principal Investigator: Josep Tabernero, M.D., Ph.D., Vall d'Hebron University Hospital (HUVH)

Study record dates

Study Major Dates

• Study Start (Estimated): August 29, 2026
• Primary Completion (Estimated): November 29, 2027
• Study Completion (Estimated): July 4, 2028

Study Registration Dates

• First Submitted: June 25, 2026
• First Submitted That Met QC Criteria: July 3, 2026
• First Posted (Actual): July 9, 2026

Study Record Updates

• Last Update Posted (Actual): August 18, 2026
• Last Update Submitted That Met QC Criteria: August 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Colorectal Cancer
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: 109S01; 2026-526235-19-00 (Ctis); CADENCIA-01 (Other Identifier: SOTIO Biotech a.s.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No