First in Human Study of M1069 in Advanced Solid Tumors

NCT05198349 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: MS201929_0032
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 3

Brief Summary

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

Conditions

Metastatic or Locally Advanced Unresectable Solid Tumors

Keywords

Adenosine antagonist; Adenosine receptor A2A/A2B antagonist; M1069

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose-Limiting Toxicities (DLTs)

  A DLT was defined as any AE, per National Cancer Institute - Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0), assessed by the Investigator or Sponsor at any dose, unrelated to underlying disease, prior/concomitant medication, or condition, occurring during the DLT observation period. DLTs included Grade more than equal to (≥) 3 thrombocytopenia with bleeding, excluding isolated Grade 4 lymphopenia without symptoms or Grade 4 neutropenia/thrombocytopenia less than (\<) 7 days without signs. Other DLTs were Hy's Law hepatotoxicity without clear cause, vision changes (≥5-line Best Corrected Visual Acuity (BCVA) loss, BCVA \<20/160, MD \>9 decibel (dB), macular thickness \>25 percentage (%)), severe eye disorders limiting self-care, ≥5-day drug interruption to prevent DLT.

  Cycle 1 (first 21 days after first study drug administration)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment Related TEAEs and Serious TEAEs

  An AE can be any unfavorable and unintended sign, symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. For surgical or diagnostic procedures, the condition/illness leading to such a procedure is considered as the AE rather than the procedure itself. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both serious TEAEs and non-serious TEAEs. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization, results in persistent disability. Treatment Related TEAEs are also reported.

  Up to 16 months

Secondary Outcomes (9)

• Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Time of Last Measurable Concentration (AUC0-tlast) of M1069

  Day 8 and 15 of Cycle 1 and Day 1 of Cycle 4 (each cycle is of 21 days)

• Area Under Plasma Concentration Time Curve From Time Zero to 24, Divided by Dose (AUC [0-24]/D) of M1069

  Day 8 and 15 of Cycle 1 and Day 1 of Cycle 4 (each cycle is of 21 days)

• Maximum Observed Plasma Concentration (Cmax) of M1069

  Day 8 and 15 of Cycle 1 and Day 1 of Cycle 4 (each cycle is of 21 days)

• Maximum Observed Plasma (Peak) Drug Concentration, by Dose (Cmax/D)

  Day 8 and 15 of Cycle 1 and Day 1 of Cycle 4 (each cycle is of 21 days)

• Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax)

  Day 8 and 15 of Cycle 1 and Day 1 of Cycle 4 (each cycle is of 21 days)

Study Arms (1)

M1069

EXPERIMENTAL

Drug: M1069

Interventions

M1069 DRUG

Participants received escalated oral dose of M1069, twice daily (BID) until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from study intervention.

M1069

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who had 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 The Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: collaborator
• EMD Serono Research & Development Institute, Inc.: lead

Study Sites (3)

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Sarah Cannon Research Institute (SCRI) (The SCRI Oncology Research Consortium)

Nashville, Tennessee, 37203, United States

Location

Princess Margaret Cancer Centre

Toronto, Canada

Location

Related Links

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

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  EMD Serono Research & Development Institute, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2022
• First Posted: January 20, 2022
• Study Start: March 2, 2022
• Primary Completion: May 9, 2023
• Study Completion: August 10, 2023
• Last Updated: April 22, 2026
• Results First Posted: April 22, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); CA (1)