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

March 30, 2026 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. The dose escalation is completed, Part 2 of the study is ongoing.

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.

In part 2, up to 30 evaluable patients with locally advanced, unresectable or metastatic non-small-cell cancer (NSCLC), no longer eligible for approved, available standard therapies and having tumour harbouring MET exon14 skipping mutation from an assessment not older than 3 months, will received DO-2 at the selected dose.

Study Type

Interventional

Enrollment (Estimated)

55

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
  • France
      • Bordeaux, France
      • Lille, France
        • Recruiting
        • Institut Cœur Poumon - CHU Lille
        • Contact:
      • Lyon, France
      • Marseille, France, 13385
        • Not yet recruiting
        • Hôpitaux Universitaires de Marseille Timone
        • Contact:
      • Nice, France
      • Rennes, France
        • Recruiting
        • Centre Hospitalier Universitaire De Rennes
        • Contact:
      • Villejuif, France
  • Netherlands
      • Nijmegen, Netherlands
      • Rotterdam, Netherlands
        • Recruiting
        • Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
        • Contact:
          • Phone Number: +31107041733
        • Contact:

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 locally advanced, unresectable or metastatic NSCLC, no longer eligible for approved, available standard therapies. To be entered patients must have proven MET exon 14 skipping mutation, determined by local next generation sequencing (NGS), whole exome sequencing (WES), whole transcriptome sequencing (WTS) or other genomic analysis methods, from an assessment not older than 3 months
  • 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 with serum creatinine <1 x institutional UNL and GFR within normal range
  • 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:

  • tumour harbouring other known oncogenic mutations promoting tumour growth
  • major surgery within 3 weeks before enrolment
  • 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
  • inability or unwillingness to swallow capsules and malabsorption syndrome or other condition that would interfere with enteral absorption

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: Expansion Cohort
Oral administration, once a day for 28 days, in a 4-week cycle of DO-2 at the selected dose
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 specific treatment-related adverse events (TRAEs)
Time Frame: Baseline through study completion, an average of 12 months

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 through study completion, an average of 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective responses rate (ORR)
Time Frame: Baseline through study completion, an average of 12 months
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 12 months
Duration of response (DoR)
Time Frame: Baseline through study completion, an average of 12 months
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 12 months
Disease Control Rate (DCR)
Time Frame: Baseline through study completion, an average of 12 months
Rate of patients who achieve either a Complete Response (CR) or a Partial Response (PR) or Stable Disease (SD) at Week 6 and Week 14
Baseline through study completion, an average of 12 months
Progression-free survival (PFS)
Time Frame: Baseline through study completion, an average of 12 months
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 12 months
Overall survival (OS)
Time Frame: Baseline through study completion, an average of 12 months
OS defined as the time from the first dose to death from any cause.
Baseline through study completion, an average of 12 months

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)

September 1, 2027

Study Completion (Estimated)

September 1, 2028

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)

April 3, 2026

Last Update Submitted That Met QC Criteria

March 30, 2026

Last Verified

March 1, 2026

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

product manufactured in and exported from the U.S.

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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