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

DeuterOncology

Status and phase: Active, not recruiting; Phase 1

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

Treatments: Drug: DO-2

Study type: Interventional

Funder types: Industry

Identifiers

NCT05752552

DO2.22.01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 25 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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25 participants in 7 patient groups

Cohort 1 (starting dose)

Experimental group

Description:

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

Treatment:

Drug: DO-2

Cohort 2 (dose level 2)

Experimental group

Description:

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

Treatment:

Drug: DO-2

Cohort 3 (dose level 3)

Experimental group

Description:

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

Treatment:

Drug: DO-2

Cohort 4 (dose level 4)

Experimental group

Description:

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

Treatment:

Drug: DO-2

Cohort 5 (dose level 5)

Experimental group

Description:

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

Treatment:

Drug: DO-2

Cohort 6 (dose level 6)

Experimental group

Description:

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

Treatment:

Drug: DO-2

Cohort 7 (dose level 7)

Experimental group

Description:

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

Treatment:

Drug: DO-2