First in Human Study of M1069 in Advanced Solid Tumors

Phase 1TerminatedNCT05198349

EMD Serono Research & Development Institute, Inc.15 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Metastatic or Locally Advanced Unresectable Solid Tumors

Interventions

M1069DRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (3)

Hackensack University Medical Center

Hackensack, New Jersey, United States

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

Nashville, Tennessee, United States

Princess Margaret Cancer Centre

Toronto, Canada

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Up to 16 months

Secondary Outcomes

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

Data from ClinicalTrials.gov

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