First in Human Study of M1069 in Advanced Solid Tumors

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

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic or Locally Advanced Unresectable Solid Tumors
• Intervention / Treatment: Drug: M1069

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Toronto, Canada
    • Princess Margaret Cancer Centre
• United States
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute (SCRI) (The SCRI Oncology Research Consortium)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: M1069	Drug: M1069; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, EMD Serono Research & Development Institute, Inc.

Publications and helpful links

Helpful Links

• US Medical Information website, Medical Resources
• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2022
• Primary Completion (Actual): May 9, 2023
• Study Completion (Actual): August 10, 2023

Study Registration Dates

• First Submitted: January 5, 2022
• First Submitted That Met QC Criteria: January 5, 2022
• First Posted (Actual): January 20, 2022

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Adenosine antagonist; Adenosine receptor A2A/A2B antagonist; M1069
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: MS201929_0032

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://bit.ly/IPD21

Drug and device information, study documents

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