First-in-human Phase I Study to Evaluate Safety, Tolerability and Antineoplastic Activity of OATD-02 in Patients With Selected Advanced and/or Metastatic Solid Tumours

Study Overview
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Brief Summary
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The goal of this clinical trial is to learn if the OATD-02 administration (orally) in monotherapy is safe and has the pharmacodynamic potential to restore and enhance tumour responses to immunotherapy through increased arginine levels or intrinsic anti-tumour activity in participants with advanced metastatic colorectal cancer, ovarian cancer, renal cancer or pancreatic cancer.

Detailed Description
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In this study, subjects suitable for enrollment will be identified by the investigators involved in the study. These subjects will be identified through contact with these investigators and referred for enrollment per protocol. This protocol will include determining enrollment suitability based on inclusion and exclusion criteria. Study scheme is based on Modified Bayesian Optimal Interval (BOIN) design. The BOIN design works by partitioning the probability of toxicity into a set of intervals. This design makes dose-selection decisions determined by the interval in which the probability of toxicity for the current dose is believed to reside. BOIN seeks a dose with probability of toxicity close to some pre-specified target level. Total number of patients will be 30 (plus 10 replacements if Dose Limiting Toxicity (DLT) is not evaluable). Study treatment will be up to 6 months.

Official Title
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An Open-label, Multicentre, Dose-escalation, First-in-human Phase I Study to Evaluate Safety, Tolerability and Antineoplastic Activity of OATD-02 in Patients With Selected Advanced and/or Metastatic Solid Tumours (Colorectal Cancer, Ovarian Cancer, Pancreatic Cancer or Renal Cell Carcinoma)

Conditions
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Advanced Ovarian Carcinoma, Advanced Renal Cell Carcinoma, Advanced Pancreatic Carcinoma, Advanced Colorectal Carcinoma, Metastatic Pancreatic Carcinoma, Metastatic Colorectal Carcinoma, Metastatic Renal Cell Carcinoma, Metastatic Ovarian Carcinoma

Intervention / Treatment
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* Drug: OATD-02


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of understanding and complying with protocol requirements. Male or female patient aged ≥18 years at Screening. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Histologically or cytologically confirmed advanced and/or metastatic colorectal cancer, renal cell cancer, or pancreatic cancer or recurrent serous ovarian cancer (platinum-resistant/ineligible to receive platinum-based chemotherapy), that either progressed or relapsed after all relevant standard of care cancer therapies (at least 1 line of systemic cancer therapy). Written informed consent given by the patient before the initiation of any study procedures. Exclusion Criteria: Unable to take oral medications. Clinically active central nervous system metastases and/or carcinomatous meningitis. Major surgery within 30 days before the first IMP dose. Pregnant or breastfeeding women. Known allergy to excipients of the IMP. Severe, uncontrolled systemic disease which in the opinion of the investigator, would compromise the safety of the patient or the patient's ability to participate in the study. Participation in another clinical study within 4 weeks before the first IMP dose.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OATD-02<br> | Drug: OATD-02<br>* Boin Design Scheme will be applied for dose escalation. Dose will start with 2.5mg o.d., the desicion about dose escalations will be made based on the occurence of DLT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nature, frequency and severity of adverse events (AEs) |  | 6 months | 
| Occurence of DLTs |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters for OATD-02: CMax |  | 6 months | 
| Anti-tumour activity parameters (Objective Response Rate (ORR), Duration of Response (DoR), PFS (Progression Free Survival) followed up to the End of Study Visit |  | 6 months | 
| PK parameter: Tmax |  | 6 months | 
| PK parameter Cmin |  | 6 months | 
| PK parameter: AUCO-24 |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, renal cancer, ovarian cancer, colorectal cancer, solid tumors