Testing the safety and effects of DO-2 in patients with advanced solid tumors

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 testing a new drug called DO-2 to see if it's safe and how it works for people with advanced solid tumors that have specific genetic changes.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 55 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: DeuterOncology (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 13 sites (Brussels and 12 other locations)
• Trial ID: NCT05752552 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, open-label, Phase 1 dose escalation study evaluating the safety and pharmacokinetics of DO-2 in patients with advanced or refractory solid tumors that have MET aberrations. The study consists of two parts, with an initial single-patient enrollment per cohort followed by a three-patient enrollment once grade 2 toxicity is observed. Patients will receive DO-2 orally, and the study aims to determine the appropriate dosing and safety profile of the drug.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced or refractory solid tumors that have specific MET mutations or amplifications.

Not a fit: Patients with solid tumors that do not have MET aberrations or those who are eligible for approved therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced solid tumors who have no available approved therapies.

How similar studies have performed: Other studies targeting MET aberrations in solid tumors have shown promise, indicating potential for success with this approach.

Eligibility criteria

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

Where this trial is running

Brussels and 12 other locations

• Institut Roi Albert II - UC Louvain — Brussels, Belgium (Recruiting)
• Uza — Edegem, Belgium (Recruiting)
• Universitair Ziekenhuis Gent — Ghent, Belgium (Recruiting)
• UZ Leuven — Leuven, Belgium (Recruiting)
• Institut Bergonie — Bordeaux, France (Recruiting)
• Institut Cœur Poumon - CHU Lille — Lille, France (Recruiting)
• Centre Léon Bérard — Lyon, France (Recruiting)
• Hôpitaux Universitaires de Marseille Timone — Marseille, France (Not_yet_recruiting)
• Centre Antoine Lacassagne — Nice, France (Not_yet_recruiting)
• Centre Hospitalier Universitaire De Rennes — Rennes, France (Recruiting)
• Institut Gustave Roussy — Villejuif, France (Not_yet_recruiting)
• Radboud UMC — Nijmegen, Netherlands (Recruiting)
• Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC) — Rotterdam, Netherlands (Recruiting)

Study contacts

• Study coordinator: Timothy Perera, PhD

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