Study to Determine the Safety and Pharmacokinetics of DO-2 in Patients With Advanced or Refractory Solid Tumours

March 13, 2024 updated by: DeuterOncology

A Phase 1 Study to Determine the Safety, and Pharmacokinetics of the Selective MET Kinase Inhibitor, DO-2 in Patients With Advanced or Refractory Solid Tumours

This study is a first-in-human, open-label, 2-part, Phase 1 dose escalation study of DO-2, administered orally to patients with advanced or refractory solid tumours, with MET aberrations, and no available, approved therapeutic alternative.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In Part 1, a Simon Design 3 accelerated titration design will be followed. One patient will be enrolled per cohort, until grade 2 toxicity is observed. Three sequential patients per cohort will be enrolled thereafter, with a minimum of 1 week between first dose administration in the first patient and the subsequent ones, in those latter cohorts.

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Belgium
      • Bruxelles, Belgium
      • Edegem, Belgium
        • Recruiting
        • UZA
        • Contact:
      • Gent, Belgium, 9000
        • Recruiting
        • Universitair Ziekenhuis Gent
        • Contact:
          • Sylvie Rottey, Prof. MD.
  • France
      • Dijon, France
        • Not yet recruiting
        • Centre Georges-François Leclerc - CHU Dijon
        • Contact:
          • François Ghiringhelli, Prof. MD
      • Lille, France
        • Not yet recruiting
        • Institut Cœur Poumon - CHU Lille
        • Contact:
          • Alexis Cortot, Prof. MD
      • Lyon, France
        • Not yet recruiting
        • Centre Leon Berard
        • Contact:
          • Aurélie Swalduz, MD
  • Netherlands
      • Nijmegen, Netherlands
        • Recruiting
        • Radboud UMC
        • Contact:
          • Carla Van Herpen, Prof. MD
      • Rotterdam, Netherlands
        • Recruiting
        • Erasmus Medical Centre
        • Contact:
        • Contact:
          • Phone Number: +31107041733

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 18 years or older

  • histologically or cytologically confirmed advanced or refractory solid tumour and no longer eligible for approved, available standard therapies. Tumour types must have:

    1. proven MET activating mutations, determined by previous next generation sequencing (NGS), whole exome sequencing (WES), whole transcriptome sequencing (WTS) or other genomic analysis methods, or
    2. proven amplification (≥ 10 copies) on archived tumour tissue. or
    3. Hereditary Renal Papillary Cancer
  • measurable disease in accordance with RECIST 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  • adequate bone marrow function, without the support of cytokines
  • adequate liver function
  • adequate renal function
  • agree to follow the contraception requirements of the trial
  • signed informed consent, indicating study patients understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

  • major surgery within 3 weeks before enrollment
  • chemotherapy (in the case of nitrosoureas and mitomycin C within 6 weeks), radiotherapy, immunotherapy, or any other study drug within 3 weeks before study drug administration
  • antibody based cancer therapy within 4 weeks before administration of the first dose of DO-2
  • patients who became progressive on previous treatment with a MET-kinase inhibitor

  • patients with brain metastases are excluded unless all of the following criteria are met:

    1. CNS lesions are asymptomatic and previously treated
    2. No ongoing requirement for corticosteroids as therapy for CNS metastases
    3. Imaging demonstrates stability of disease > 28 days from last treatment for CNS metastases
  • leptomeningeal involvement (leptomeningeal carcinomatosis)
  • history of uncontrolled heart disease including unstable angina, congestive heart failure, myocardial infarction within preceding 12 months, clinically significant rhythm or conduction abnormality, congenital long QT syndrome, obligate use of a cardiac pacemaker, QTc at screening greater than 450 milliseconds in males and greater than 470 milliseconds in females
  • uncontrolled arterial hypertension despite appropriate therapy
  • positive pregnancy test (urinary beta-hCG) at screening (applicable to women of child-bearing potential who are sexually active)
  • mental status alteration or history of major psychiatric illness, which may potentially impair patient's compliance with study procedures
  • signs and symptoms of active infection requiring systemic therapy
  • other medical condition (e.g. pre-existing kidney dysfunction) that in the opinion of the investigator makes it undesirable for a patient to participate

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1 (starting dose)
Oral administration, once a day for 28 days, in a 4-week cycle
Drug: DO-2
Deuterated MET kinase inhibitor
Experimental: Cohort 2 (dose level 2)
Oral administration, once a day for 28 days, in a 4-week cycle
Drug: DO-2
Deuterated MET kinase inhibitor
Experimental: Cohort 3 (dose level 3)
Oral administration, once a day for 28 days, in a 4-week cycle
Drug: DO-2
Deuterated MET kinase inhibitor
Experimental: Cohort 4 (dose level 4)
Oral administration, once a day for 28 days, in a 4-week cycle
Drug: DO-2
Deuterated MET kinase inhibitor
Experimental: Cohort 5 (dose level 5)
Oral administration, once a day for 28 days, in a 4-week cycle
Drug: DO-2
Deuterated MET kinase inhibitor
Experimental: Cohort 6 (dose level 6)
Oral administration, once a day for 28 days, in a 4-week cycle
Drug: DO-2
Deuterated MET kinase inhibitor
Experimental: Cohort 7 (dose level 7)
Oral administration, once a day for 28 days, in a 4-week cycle
Drug: DO-2
Deuterated MET kinase inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of subjects who experience Dose Limiting Toxicities (DLTs)
Time Frame: Baseline up to Week 4
Only toxicities that occur during Cycle 1 will be considered for the purposes of defining DLT and for dose escalation, but toxicities that occur in all cycles will be recorded and considered in decisions about the Maximum Tolerated Dose. DLTs are defined as toxicities that meet pre-defined severity criteria. Toxicity grading will be performed in accordance with NCI-CTC Version 5.0.
Baseline up to Week 4
Number of subjects who experience specific treatment-related adverse events (TRAEs)
Time Frame: Baseline up to Week 36

Number of subjects with specific treatment-related adverse events for each dose group.

AE refers to any untoward medical occurrence or deterioration of existing medical event after the subject signed the ICF, whether or not considered related to the study treatment. TRAEs are any event that occurs after the subject has received study treatment. AE grading will be performed in accordance with NCI-CTC Version 5.0.
Baseline up to Week 36
Determination of the Maximum Tolerated Dose (MTD)
Time Frame: Baseline up to Week 4
The MTD in milligram is defined as the highest dose at which less than one third of the subjects in a dose level cohort experience DLT.
Baseline up to Week 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum observed concentration (Cmax) and Area under the curve (AUC) of DO-2
Time Frame: Baseline up to Day 23
Determine the Cmax and AUC of DO-2 and its main metabolites in plasma sampled at different timepoints during Cycle 1.
Baseline up to Day 23
Time over treshold (ToT) for DO-2
Time Frame: Baseline up to Day 23
Time by which the observed concentration of DO-2 in plasma is above the expected efficacy treshold.
Baseline up to Day 23
Objective responses seen in Part I and objective response rate (ORR) in Part II
Time Frame: Baseline through study completion, an average of 36 weeks
ORR is defined as the proportion of subjects with confirmed CR or confirmed PR. Radiologic assessment will be repeated after every second cycle (or more frequently if clinically indicated) and using same methodology as at baseline. Response assessment (radiologic) will be determined in accordance with RECIST (version 1.1) and current disease specific solid tumour response criteria.
Baseline through study completion, an average of 36 weeks
Duration of response (DoR)
Time Frame: Baseline through study completion, an average of 36 weeks
DoR is defined as the duration from the first documentation of objective response to the first documented disease progression (based on RECIST Version 1.1) or death due to any cause, whichever occurs first.
Baseline through study completion, an average of 36 weeks
Progression-free survival (PFS)
Time Frame: Baseline through study completion, an average of 36 weeks
PFS is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever occurs first (based on RECIST Version 1.1).
Baseline through study completion, an average of 36 weeks
Overall survival (OS)
Time Frame: Baseline through study completion, an average of 36 weeks
OS defined as the time from the first dose to death from any cause.
Baseline through study completion, an average of 36 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

DeuterOncology

Investigators

  • Study Chair: Jaap Verweij, MD, CMO DeuterOncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 20, 2022

Primary Completion (Estimated)

October 1, 2024

Study Completion (Estimated)

April 1, 2025

Study Registration Dates

First Submitted

February 7, 2023

First Submitted That Met QC Criteria

March 1, 2023

First Posted (Actual)

March 2, 2023

Study Record Updates

Last Update Posted (Actual)

March 15, 2024

Last Update Submitted That Met QC Criteria

March 13, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DO2.22.01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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