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

NCT05752552 | Active Not Recruiting Phase 1

• 1 other identifier: DO2.22.01
• Study Type: interventional
• Target: 25
• Locations: 3 countries
• Sites: 8

Brief Summary

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.

Conditions

Adult Solid Tumor; Advanced Solid Tumor; Refractory Tumor; Non-small Cell Lung Cancer; Non-small Cell Carcinoma; Lung Cancer; Hereditary Renal Papillary Cancer

Outcome Measures

Primary Outcomes (3)

• Number of subjects who experience Dose Limiting Toxicities (DLTs)

  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)

  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)

  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 Outcomes (6)

• Maximum observed concentration (Cmax) and Area under the curve (AUC) of DO-2

  Baseline up to Day 23

• Time over treshold (ToT) for DO-2

  Baseline up to Day 23

• Objective responses seen in Part I and objective response rate (ORR) in Part II

  Baseline through study completion, an average of 36 weeks

• Duration of response (DoR)

  Baseline through study completion, an average of 36 weeks

• Progression-free survival (PFS)

  Baseline through study completion, an average of 36 weeks

Study Arms (7)

Cohort 1 (starting dose)

EXPERIMENTAL

Oral administration, once a day for 28 days, in a 4-week cycle

Drug: DO-2

Cohort 2 (dose level 2)

EXPERIMENTAL

Oral administration, once a day for 28 days, in a 4-week cycle

Drug: DO-2

Cohort 3 (dose level 3)

EXPERIMENTAL

Oral administration, once a day for 28 days, in a 4-week cycle

Drug: DO-2

Cohort 4 (dose level 4)

EXPERIMENTAL

Oral administration, once a day for 28 days, in a 4-week cycle

Drug: DO-2

Cohort 5 (dose level 5)

EXPERIMENTAL

Oral administration, once a day for 28 days, in a 4-week cycle

Drug: DO-2

Cohort 6 (dose level 6)

EXPERIMENTAL

Oral administration, once a day for 28 days, in a 4-week cycle

Drug: DO-2

Cohort 7 (dose level 7)

EXPERIMENTAL

Oral administration, once a day for 28 days, in a 4-week cycle

Drug: DO-2

Interventions

DO-2 DRUG

Deuterated MET kinase inhibitor

Cohort 1 (starting dose); Cohort 2 (dose level 2); Cohort 3 (dose level 3); Cohort 4 (dose level 4); Cohort 5 (dose level 5); Cohort 6 (dose level 6); Cohort 7 (dose level 7)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• proven amplification (≥ 10 copies) on archived tumour tissue. or
• 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.

You may not qualify if:

• 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:
• CNS lesions are asymptomatic and previously treated
• No ongoing requirement for corticosteroids as therapy for CNS metastases
• 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

Sponsors & Collaborators

• DeuterOncology: lead

Study Sites (8)

Institut Roi Albert II - UC Louvain

Brussels, Belgium

Location

UZA

Edegem, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Centre Georges-François Leclerc - CHU Dijon

Dijon, France

Location

Institut Cœur Poumon - CHU Lille

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

Radboud UMC

Nijmegen, Netherlands

Location

Erasmus Medical Centre

Rotterdam, Netherlands

Location

Related Links

• DeuterOncology Internet site

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jaap Verweij, MD

  CMO DeuterOncology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2023
• First Posted: March 2, 2023
• Study Start: December 20, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3); BE (3); NL (2)