First in Human Study of M1069 in Advanced Solid Tumors

Phase 1

Terminated

• Conditions: Metastatic or Locally Advanced Unresectable Solid Tumors
• Interventions: Drug: M1069

• Registration Number: NCT05198349
• Lead Sponsor: EMD Serono Research & Development Institute, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-01-05
• Study First Submitted QC: 2022-01-05
• Study First Posted: 2022-01-20
• Study Start: 2022-03-02
• Primary Completion: 2023-05-09
• Study Completion: 2023-08-10
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-20
• Last Update Posted: 2024-11-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 15

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
M1069	M1069	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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)
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)
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
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
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 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)

Trial Locations

Locations (3)

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Canada

Sarah Cannon Research Institute (SCRI) (The SCRI Oncology Research Consortium); 🇺🇸 Nashville, Tennessee, United States