First in Human Study of M1069 in Advanced Solid Tumors

Metastatic or Locally Advanced Unresectable Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05198349
• Other study ID #: MS201929_0032
• Status: Terminated
• Phase: Phase 1
• Start date: March 2, 2022
• Est. completion date: August 10, 2023

Study information

• Verified date: October 2023
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: August 10, 2023
• Est. primary completion date: May 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metastatic or Locally Advanced Unresectable Solid Tumors
• Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Sarah Cannon Research Institute (SCRI) (The SCRI Oncology Research Consortium)	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	Duration of Response (DoR)		Time from first dose of study drug up to planned assessment at 18.2 months
Secondary	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
Secondary	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)

External Links

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