Clinical trial NCT05752552: Study to Determine the Safety and Pharmacokinetics of DO-2 in Patients with Advanced or Refractory Solid Tumours
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Adult Solid Tumor
Advanced Solid Tumor
Refractory Tumor
Non-small Cell Lung Cancer
Non-small Cell Carcinoma
Lung Cancer
Hereditary Renal Papillary Cancer
Lead sponsor: DeuterOncology
Sponsor class: INDUSTRY
First posted: 2023-03-02
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of subjects who experience Dose Limiting Toxicities (DLTs)
timeFrame: Baseline up to Week 4
measure: Number of subjects who experience specific treatment-related adverse events (TRAEs)
timeFrame: Baseline up to Week 36
measure: Determination of the Maximum Tolerated Dose (MTD)
timeFrame: Baseline up to Week 4
Secondary outcomes:
measure: Maximum observed concentration (Cmax) and Area under the curve (AUC) of DO-2
timeFrame: Baseline up to Day 23
measure: Time over treshold (ToT) for DO-2
timeFrame: Baseline up to Day 23
measure: Objective responses seen in Part I and objective response rate (ORR) in Part II
timeFrame: Baseline through study completion, an average of 36 weeks
measure: Duration of response (DoR)
timeFrame: Baseline through study completion, an average of 36 weeks
measure: Progression-free survival (PFS)
timeFrame: Baseline through study completion, an average of 36 weeks
measure: Overall survival (OS)
timeFrame: Baseline through study completion, an average of 36 weeks
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Institut Roi Albert II - UC Louvain
city: Edegem
country: Belgium
facility: UZA
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Dijon
country: France
facility: Centre Georges-François Leclerc - CHU Dijon
city: Lille
country: France
facility: Institut Cœur Poumon - CHU Lille
city: Lyon
country: France
facility: Centre Léon Bérard
city: Nijmegen
country: Netherlands
facility: Radboud UMC
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Centre
Study officials:
affiliation: CMO DeuterOncology
name: Jaap Verweij, MD
role: STUDY_CHAIR
References: