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 was 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 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
• 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 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Time of Last Measurable Concentration (AUC0-tlast) of M1069	The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down).	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	AUC [0-24]/D is the Area under plasma concentration time curve from time zero to 24 divided by dose (AUC [0-24]/D) of M1069. Calculated using the mixed log-linear trapezoidal rule (linear up, log down).	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	Cmax is the maximum observed plasma concentration and was obtained directly from the concentration versus time curve.	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)	Cmax/D is the maximum observed plasma concentration by dose. Cmax was obtained directly from the concentration versus time curve, divided by Dose of M1069.	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)	The time to reach the maximum observed plasma concentration (Tmax) was obtained directly from the concentration versus time curve.	Day 8 and 15 of Cycle 1 and Day 1 of Cycle 4 (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	OR is defined as a best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all target lesions. Number of participants with BOR of CR or PR was reported.	Time from first observation of response (CR or PR) up to planned assessment at 17.3 months
Duration of Response (DoR)	DoR is the time from when the complete response (CR) or partial response (PR) (whichever is first) criteria are first met until disease progression (PD) or death due to any cause within the period of 2 scheduled tumor assessments after the last tumor assessment, whichever occurs first. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.	Time from first observation of response (CR or PR) up to planned assessment at 17.3 months
Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), as Assessed by Investigator	PFS is defined as the time (in months) from first administration of study intervention to the date of the first documentation of progression disease (PD) or death due to any cause within the period of 2 scheduled tumor assessments after the last tumor assessment, whichever occurs first. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was to be estimated using Kaplan-Meier (KM) plots.	Time from first administration of study intervention to the date of the first documentation of progression disease (PD) or death due to any cause within, whichever occurs first, assessed up to maximum of 17.3 months
Change From Baseline in Corrected QT (QTc) Interval	A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 10 minutes using an ECG machine. Change from baseline in QTc interval was reported. In the Timeframe the "C" refers to Cycle, "D" refers to Day and "h" refers to the hours.	Cycle (C)1Day (D)1: 1h, 2h, 4h, 6h, 8h post-dose; C1D8: 15min predose, 1h, 2h, 4h, 6h, 8h post-dose; C1D15: predose; C2D1: predose, 2h post-dose; C4D1, C6D1, C10D1, C12D1, C14D1, C18D1(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): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Adenosine antagonist; Adenosine receptor A2A/A2B antagonist; M1069
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis
• 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