First in Human Study of M1069 in Advanced Solid Tumors

Study Overview
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Brief Summary
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The main purpose of this study is to determine the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and early signs of efficacy of M1069 in participants with advanced solid malignancies.

Official Title
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First-in-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of M1069 in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors

Conditions
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Metastatic or Locally Advanced Unresectable Solid Tumors

Intervention / Treatment
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* Drug: M1069


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who have histologically or cytologically proven locally advanced or metastatic solid malignancies and who are refractory to or have progressed under standard treatment or for whom standard treatment is not expected to deliver clinical benefit Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at Screening Adequate hematological function, hepatic function and renal function Ability to swallow oral dose forms (for example [e.g.] capsules) Fresh tumor biopsies mandatory for participants at Dose level 2 (DL2) and 6 participants upon potential determination of Recommended Dose for Expansion (RDE). Providing consent to fresh tumor biopsies taken during the Screening period and an on-treatment biopsy is mandatory Life expectancy of at least 12 weeks according to Investigator judgement Measurable disease according to RECISTv1.1 Other protocol defined inclusion criteria could apply Exclusion Criteria: Persisting toxicity related to prior therapy Grade greater than (>) 1 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0, however, alopecia, sensory neuropathy hypothyroidism and diabetes mellitus Grade less than or equal to (<=) 2, despite treatment, are allowed Prior organ transplantation including allogeneic stem cell transplantation Participants with known brain metastases, except those meeting the following criteria: a) Brain metastases that have been treated locally and are clinically stable for at least 4 weeks prior to the start of treatment; b) No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) Participants must be either off steroids or on a stable or decreasing dose of < 10 milligrams (mg) daily prednisone (or equivalent) Current significant cardiac conduction abnormalities, including corrected QT interval (QTcF, corrected with Fridericia formula) prolongation of > 470 milliseconds (ms) or impaired cardiovascular function, ventricular tachycardia (including Torsades de Pointes), or a history of paroxysmal atrial fibrillation, serious cardiac arrhythmia and family history of sudden death or long QT syndrome Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent including but not limited to inflammatory bowel diseases, autoimmune hepatitis, interstitial lung disease of immunologic origin, systemic lupus erythematosus, et cetera (etc.), with the following exceptions: a) Participants with diabetes type I, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible Significant acute or chronic fungal, bacterial and/or viral infections requiring systemic therapy including coronavirus disease of 2019 (COVID-19) Known hypersensitivity to the trial treatment or to one or more of the excipients Other protocol defined exclusion criteria could 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M1069<br> | Drug: M1069<br>* Participants will receive escalated oral dose of M1069, twice daily (BID) until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from study intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Profile as Assessed by Incidence of Adverse Events (AEs), Treatment-Related AEs and Dose-Limiting Toxicities (DLTs) |  | Time from first dose of study drug up to planned assessment at 18.2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamic Assessment by Phosphorylated cAMP Response Element-binding Protein (pCREB) Level in ex-vivo Stimulated Blood |  | Pre-dose up to 8 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 8; Pre-dose on Cycle 2 Day 1 (each cycle is of 21 days) | 
| Change from Baseline in Tumor Microenvironment (TME) in Available Paired Tumor Biopsies at Cycle 2 Day 15 |  | Baseline, Cycle 2 Day 15 (each cycle is of 21 days) | 
| Pharmacokinetic (PK) Plasma Concentrations of M1069 |  | Pre-dose up to 24 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is of 21 days) | 
| Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), as Assessed by Investigator |  | Time from first dose of study drug up to planned assessment at 18.2 months | 
| Duration of Response (DoR) |  | Time from first dose of study drug up to planned assessment at 18.2 months | 
| Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), as Assessed by Investigator |  | Time from first dose of study drug up to planned assessment at 18.2 months | 
| Change from Baseline in Corrected QT (QTc) Interval Over Time |  | Pre-dose (Baseline) up to 8 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is of 21 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adenosine antagonist, Adenosine receptor A2A/A2B antagonist, M1069