A Study of EP0031 (Lunbotinib) in Patients With Advanced RET-altered Malignancies

Официальное название

A Modular, Open-label, Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of EP0031 in Patients With Advanced RET-altered Malignancies

Обзор

The aim of this study is to assess the safety, side effects and effectiveness of EP0031 (Lunbotinib) in patients with advanced RET-altered non-small cell lung cancer (NSCLC) in monotherapy and in combination with standard of care (SOC) chemotherapy.

Подробное описание

EP0031 is being investigated in this modular, interventional Phase I/II dose escalation and dose expansion study to investigate the optimal dose in adult patients with advanced RET-altered NSCLC. Currently there are no approved RET-targeted treatments for patients who progress on first-generation Selective RET Inhibitors (SRIs). However, it is proposed that EP0031 can overcome resistance mechanisms to first generation SRIs, as EP0031 is a potent and selective RET inhibitor with broad activity against common RET fusions and mutations. Phase I (dose escalation and optimization) has completed for this study and determined the Recommended Phase 2 Dose (RP2D). The study is now in Phase 2, assessing the safety, tolerability and efficacy of EP0031 given in combination with SOC chemotherapy in RET fusion positive NSCLC participants.

Вмешательства

• Препарат EP0031
  EP0031 is a potent next-generation selective RET-inhibitor (SRI)
• Препарат Platinum chemotherapy
  One of either Cisplatin or Carboplatin. Both agents are potent platinum-based antineoplastic/alkylating agents administered as an IV infusion according to local practice and labels.
• Препарат Pemetrexed
  Pemetrexed is a chemotherapy medication and antifolate metabolic inhibitor administered as an IV infusion according to local practice and labels.

Первичные конечные точки

• Module B: Incidence of Dose-limiting Toxicity (DLTs ) during the first 21 days of EP0031 given in combination with SOC chemotherapy treatment [Срок оценки: First 21 days of treatment]

Вторичные конечные точки (4)

• Module B: Overall Response Rate (ORR) as measured using RECIST v1.1 [Срок оценки: 12 months]
• Area under the plasma concentration versus time curve (AUC) [Срок оценки: First 24 hours after drug administered]
• Maximum Plasma Concentration (Cmax) [Срок оценки: First 24 hours after drug administered]
• Time taken for drug concentration to fall from half its original value (Half-life) [Срок оценки: First 24 hours after drug administered]

Критерии участия

Критерии включения

Applicable to all participants:

• Must be ≥18 years of age, with documented RET-altered NSCLC
• Participants should be well informed and consented about alternative treatment options including approved RET-targeted therapies
• ECOG performance status of 0 or 1 and life expectancy >3 months at screening
• Ability to understand and provide written informed consent and able to participate in all required evaluations and procedures
• Measurable disease defined by RECIST v1.1
• Must have locally advanced or metastatic NSCLC with RET fusion who are eligible to receive platinum-based doublet chemotherapy.
• First line patients: Must not have received a Selective RET inhibitor or chemotherapy. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapy, investigational agents, are permitted as long as treatment was completed at least 12 months prior. Palliative radiotherapy for symptom management (eg, bone metastases) is permitted up to 2 weeks prior to treatment start.

Критерии исключения

Participants with any of the following will not be included in the study:

• Any known major driver gene alterations other than RET.
• Spinal cord compression or brain metastases. Patients with stable brain metastases can be enrolled.
• Active infection requiring systemic antibiotic, antifungal, or antiviral medication
• Severe or uncontrolled medical condition or psychiatric condition
• Chronic glomerulonephritis or renal transplant
• Participants with active hepatitis B infection or active hepatitis C
• Participants with active HIV infection. Patients living with HIV may be eligible if they have adequate CD4+ T-cell count and no history of AIDS-defining opportunistic infections in the past 12 months
• Receipt of any strong inhibitor or inducer of CYP3A4
• Impaired hepatic or renal function, inadequate bone marrow reserve or organ function
• Any clinically important abnormalities in rhythm, conduction, or morphology on resting ECG or any factor that increases the risk of QTc prolongation or of arrhythmic events , or congestive heart failure Grade III-IV according to the New York Heart Association, myocardial infarction, or unstable angina within the previous 6 months
• Uncontrolled hypertension
• Corneal ulceration or untreated keratitis at screening

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 21 центр

• David Geffen School of Medicine at UCLA — Los Angeles
• Stanford University — Stanford
• Georgetown University — Washington D.C.
• Florida Cancer Specialist — Fort Myers
• University of Miami - Sylvester Comprehensive Cancer Center — Miami
• Florida Cancer Specialists & Research Institute — West Palm Beach
• RUSH University Medical Center — Chicago
• Northwestern University — Evanston
• … и ещё 13 центров

Испания · 7 центров

• Hospital Universitario de A Coruña — A Coruña
• Hospital Universitario Vall d'Hebron — Barcelona
• Hospital Universitario Insular de Gran Canaria — Las Palmas de Gran Canaria
• Hospital Universitario Ramon y Cajal — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Madrid Sanchinarro — Madrid
• Hospital Virgen de la Victoria de Malaga — Málaga

Италия · 6 центров

• Centro di Riferimento Oncologico IRCCS — Aviano
• IRCCSS AOU Bologna — Bologna
• Fondazione IRCCS Istituto Nazionale dei Tumori — Milan
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma
• Istituto Nazionale Tumori Regina Elena — Roma
• Azienda Ospedaliero-Universitaria San Luigi Gonzaga — Torino

Франция · 5 центров

• Institut Bergonié — Bordeaux
• Centre François Baclesse — Caen
• Centre Léon Bérard — Lyon
• Assistance Publique - Hôpitaux de Marseille — Marseille
• Institut Gustave Roussy — Paris

Великобритания · 5 центров

• University College London Hospital (UCLH) — London
• Guy's and St Thomas' Hospital NHSFT — London
• The Royal Marsden NHSFT — London
• The Christie Hospital NHSFT — Manchester
• Sheffield Teaching Hospitals NHSFT — Sheffield

Германия · 3 центра

• Charité Comprehensive Cancer Center — Berlin
• Universitätsklinikum Köln — Cologne
• Ludwig-Maximilians-Universität München (LMU) — München

ОАЭ · 3 центра

• Tawam Hospital — Al Ain City
• Sheik Shakhbout Medical City (SSMC) — Abu Dhabi
• Cleveland Clinic Abu Dhabi (CCAD) — Abu Dhabi

Польша · 2 центра

• Uniwersyteckie Centrum Kliniczne — Gdansk
• Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie — Warsaw

Идентификаторы

NCT: NCT05443126 · EP0031-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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