A Study to Evaluate Safety and Preliminary Anti-tumor Activity of Debio 0123 as Monotherapy in Adult Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study has two parts: Part 1 and Part 2. The purpose of this study in Part 1, Dose Escalation Part is to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of Debio 0123 as monotherapy with repeated dosing in adults with advanced solid tumors that recurred or progressed after prior therapy and/or for whom no standard therapy of proven benefit is available. The purpose in Part 2, Expansion Part of this study, is to characterize the safety and tolerability of Debio 0123 when administered as monotherapy at the MTD/RP2D determined during the Dose Escalation Part 1 and to evaluate the preliminary anti-tumor activity of Debio 0123 when administered as monotherapy in participants with specific solid tumor types that recurred or progressed following prior lines of therapy.

Official Title
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A Phase 1, Dose-finding Study of Debio 0123 as Monotherapy in Adult Patients With Advanced Solid Tumors, Followed by an Expansion Part to Assess Safety and Preliminary Anti-tumor Activity

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: Debio 0123


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1 dose escalation only Histologically or cytologically confirmed locally advanced or metastatic solid tumors. Measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Disease progression under or following standard therapy and/or no available standard therapy of proven benefit. Part 2 expansion only o Measurable disease per RECIST version 1.1 criteria Part 1 dose escalation and Part 2 expansion Accessible tumor for biopsy, and participant willing to undergo tumor biopsy unless archived tumor sample is available. Eastern Cooperative Oncology Group (ECOG) performance status (PS) PS 0-1. Life expectancy of at least 3 months, in the best judgment of the Investigator. Adequate bone marrow, liver biochemistry, renal function, and coagulation status. Willing to practice highly effective methods of contraception. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Exclusion Criteria: Participants with active second malignancies requiring therapy in the last 6 months, with the exception of superficial bladder cancers, ductal carcinoma in situ or other carcinomas in situ, and non-melanoma non-melanoma skin cancers (basal cell/squamous cell skin cancer) that have been treated surgically. Current use of an investigational agent or a medical device. Major surgery ≤4 weeks prior to the first dose of study treatment or who have not recovered from the surgical procedure. Brain tumors and/or brain metastases unless they are asymptomatic, stable on recent imaging (not dated more than 28 days from the inclusion date), and have not required active treatment in the last month before study entry. History of myocardial infarction or stroke within 6 months, congestive heart failure greater than New York Heart Association (NYHA) class II, unstable angina pectoris, unexplained recurrent syncope, cardiac arrhythmia requiring treatment, family history of sudden death from cardiac-related causes, or any cardiotoxicity experienced after previous chemotherapy. Known infection requiring systemic use of an antibiotic or antiviral agent. Immunization with live or live-attenuated vaccine within 28 days prior to study inclusion or planned injection of live or live-attenuated vaccines. Pregnancy or breast-feeding. Inability or unwillingness to swallow oral medication. Clinically significant gastrointestinal abnormality that would affect the absorption of the drug. Chemotherapy, monoclonal antibodies/biologics, or radiotherapy with curative intent within 28 days prior to starting study treatment. Palliative radiation for pain relief is allowed up to 1 week prior to starting study treatment. Unresolved AEs or toxicities due to previous treatments, i.e., >Grade 1 or >Grade 2 for alopecia and endocrinopathies controlled by replacement therapy (example, hypothyroidism due to immune checkpoint inhibitors) [Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.]

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose Escalation<br>Participants will receive Debio 0123 orally in escalating dose cohorts during each 21-day treatment cycle until progression of disease, unacceptable toxicity, participant's withdrawal, or Investigator's decision, whichever occurs first. | Drug: Debio 0123<br>* Debio 0123 orally during 21-day treatment cycles.<br>|
| Experimental: Part 2: Expansion<br>Debio 0123 at the RP2D established in Part 1. | Drug: Debio 0123<br>* Debio 0123 orally during 21-day treatment cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Maximum Tolerated Dose (MTD) as Determined by Percentage of Participants with Dose Limiting Toxicities (DLTs) |  | Cycle 1 (each cycle is 21 days) | 
| Part 1: Recommended Phase 2 Dose (RP2D) as Determined by Percentage of Participants with DLTs and Cumulative Safety |  | Cycle 1 (each cycle is 21 days) | 
| Part 2: Percentage of Participants with Serious Adverse Events (SAEs) |  | Up to 30 days after the last dose of study treatment (up to 13 months) | 
| Part 2: Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs) and Laboratory Abnormalities |  | Up to 30 days after the last dose of study treatment (up to 13 months) | 
| Part 2: Percentage of Participants with Treatment Discontinuations and Treatment Modifications due to Adverse Events (AEs) and Laboratory Abnormalities |  | Up to end of study treatment (up to 12 months) | 
| Part 2: Overall Response Rate (ORR) |  | From the start of study treatment until disease progression (up to 12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Percentage of Participants with SAEs |  | Up to 30 days after the last dose of study treatment (up to 13 months) | 
| Part 1: Percentage of Participants with TEAEs and Laboratory Abnormalities |  | Up to 30 days after the last dose of study treatment (up to 13 months) | 
| Part 1: Plasma Concentration of Debio 0123 | The pharmacokinetics (PK) of Debio-0123 will be evaluated in plasma. | Pre-dose and at multiple time points up to 8 hours (h) on Day 1, Cycle 1 (each cycle is 21 days) | 
| Parts 1 and 2: Anti-Tumor Activity as Assessed by Percentage of Participants with Tumor Response |  | Parts 1 and 2: Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Solid Tumors, WEE1-inhibitor