Safety, Tolerability, and Pharmacokinetics of EVT801 in Patients With Advanced Solid Tumours

NCT05114668 | Completed Phase 1 DMC

• 1 other identifier: KZA-0801-101
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

The main purpose of this study is to evaluate the safety and tolerability of EVT801 in subjects with advanced or metastatic solid tumours. The study also aims to determine the maximum tolerated dose (MTD) and / or a recommended Phase 2 dose (RP2D) of EVT801 when administered daily to subjects with advanced or metastatic solid tumours. The study comprises two stages, each with distinct purposes, patient populations, and procedures:

• Stage 1: a multiple ascending dose escalation of EVT801 to evaluate the safety and tolerability of EVT801 and to determine MTD / RP2D in subjects with advanced solid tumours.
• Stage 2: a biomarker expansion cohort, in which all subjects will receive EVT801 at the MTD / RP2D, to explore pharmacodynamic outcomes and further elucidate tolerability, activity, and pharmacokinetics.

Conditions

Solid Tumor, Adult

Keywords

cancer; solid tumors; advanced or metastatic tumors; renal cell carcinoma; soft tissue sarcoma

Outcome Measures

Primary Outcomes (2)

• MTD and / or a RP2D of EVT801 when administered daily to subjects with advanced or metastatic solid tumours.

  The MTD is defined as the highest dose administered at which fewer than one-third of patients experienced a DLT. The RP2D will be determined for Stage 1 on the basis of an overall assessment of safety, pharmacokinetics, and other information. The RP2D may be equal to, or lower than, the MTD.

  24 months

• Adverse event (AE) safety information for EVT801

  To provide safety information for EVT801 by assessing adverse events, per CTCAE v5.0.

  36 months

Secondary Outcomes (6)

• Cmax pharmacokinetic (PK) parameter of EVT801 following administration in an oral capsule formulation.

  12 months

• Tmax pharmacokinetic (PK) parameter of EVT801 following administration in an oral capsule formulation.

  12 months

• T1/2 pharmacokinetic (PK) parameter of EVT801 following administration in an oral capsule formulation.

  12 months

• AUC(0-last) and AUC(0-inf) pharmacokinetic (PK) parameter of EVT801 following administration in an oral capsule formulation.

  12 months

• CL pharmacokinetic (PK) parameter of EVT801 following administration in an oral capsule formulation.

  12 months

Study Arms (2)

Stage 1

EXPERIMENTAL

\- Stage 1 (Dose Escalation Cohorts): Stage 1 is a multiple ascending dose escalation of EVT801 in patients with advanced solid tumours to evaluate the safety and tolerability of EVT801 and to determine MTD / RP2D for further investigation.

Drug: EVT801

Stage 2

EXPERIMENTAL

\- Stage 2 (Biomarker Expansion cohorts): A biomarker expansion cohort, in which all subjects will receive EVT801 at the MTD / RP2D, will be recruited to explore pharmacodynamic outcomes and further elucidate tolerability, activity, and pharmacokinetics.

Drug: EVT801

Interventions

EVT801 DRUG

Stage 1: Patients will be dosed orally with EVT801 capsules at the dose and schedule to which they are assigned. Stage 2: Patients will be dosed orally with EVT801 capsules at the MTD / RP2D identified in Stage 1 of the study.

Stage 1; Stage 2

Eligibility Criteria

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

You may qualify if:

• Subjects of any gender who are ≥18 years of age at the time of study entry.
• Histologically-confirmed advanced or metastatic solid tumours, unresponsive to standard treatment, or for whom no standard treatment is available or appropriate.
• Measurable or evaluable disease per RECIST 1.1 criteria.
• ECOG performance status \<2.
• Life expectancy of greater than 3 months, in the opinion of the investigator.
• Able and willing to provide archived tumour samples, or to undergo pre-treatment tumour biopsy if feasible; subjects must be able to provide at least one tumour tissue sample (archived or pre-treatment biopsy) to be eligible.
• Written, signed, and dated informed consent to participate in this study in a format approved by the ethics committee.
• Adequate organ and bone marrow function at the time of screening, including:
• Haematology:
• Absolute neutrophil count (ANC) \>1.5 x 109/L.
• Platelet count of \>75 x 109/L.
• Haemoglobin \> 90g/L (without transfusion for at least 2 weeks).
• Renal Function:
• Estimated glomerular filtration rate (GFR), based on MDRD (modification of diet in renal disease) calculation, of ≥60 ml/min/1.73 m2.
• Creatinine ≤1.5 mg/dL (≤132.6 μmol/L).

You may not qualify if:

• Subjects with Grade ≥2 neuropathy, and subjects with irreversible toxicity that is not reasonably expected to be exacerbated by study participation, may be included only after consultation with the lead investigator.
• CNS tumours: symptomatic or steroid-dependent lesions. Cured lesions are acceptable.
• History of another primary malignancy, unless treated with curative intent and with no known active disease for ≥2 years prior to study entry; subjects with a history of adequately treated non-melanoma skin cancer or superficial bladder cancer or carcinoma in situ of the cervix may be enrolled if there is no evidence of residual disease.
• Current participation in another interventional clinical trial, or participation within 28 days prior to study entry.
• Clinically significant cardiac disease or impaired cardiac function, including:
• Congestive heart failure requiring treatment (New York Heart Association (NYHA) Grade ≥2).
• Left ventricular ejection fraction (LVEF) \<50%, as determined by MUGA scan or echocardiogram.
• History or current evidence of clinically significant or uncontrolled cardiac arrhythmias, atrial fibrillation, or conduction abnormality.
• Acute coronary syndromes, myocardial infarction, unstable angina, or procedures including coronary artery bypass grafting (CABG) or coronary angioplasty within 6 months prior to screening.
• Uncontrolled hyperkalemia.
• Mean (based on mean value of screening triplicate ECGs) resting corrected QT interval (QTc) \> 470 msec (for women) and \> 450 msec (for men) obtained from 3 consecutive ECGs or with QT interval \> 500 msec for one of the ECGs at screening visit and D1 predose.
• Any disease of the GI tract which renders the subject unable to take oral medications, or which might affect the absorption of oral medicines (e.g. inflammatory bowel disease, malabsorption syndrome, requirement for parenteral nutrition).
• Active haemorrhagic syndrome, or presence of tumour in contact with large vessels (e.g. neck, mediastinum, retroperitoneum).
• Acute infection within 1 week prior to starting study treatment.
• Diagnosis of SARS-CoV-2, confirmed by PCR within 3 months prior to starting study treatment, unless fully resolved with no residual symptoms.

Sponsors & Collaborators

• Kazia Therapeutics Limited: lead

Study Sites (2)

Centre Léon Bérard

Lyon, 69373, France

Location

Institut Universitaire du Cancer Toulouse - Oncopole

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis; Carcinoma, Renal Cell; Sarcoma

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasms, Connective and Soft Tissue

Study Officials

• Carlos Gomez-Roca, MD

  Institut Claudius Regaud, Toulouse, France

  PRINCIPAL INVESTIGATOR

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: October 6, 2021
• First Posted: November 10, 2021
• Study Start: November 3, 2021
• Primary Completion: November 4, 2024
• Study Completion: November 22, 2024
• Last Updated: September 2, 2025

Record last verified: 2025-08

Locations

FR (2)