A Study of Emiltatug Ledadotin (Emi-Le) in Participants With Solid Tumors

Официальное название

A Phase 1/2, First-in-human, Multicenter Study of Emiltatug Ledadotin (Emi-Le) in Participants With Solid Tumors

Обзор

A Study of Emi-Le in Participants with Solid Tumors

Подробное описание

This first-in-human (FIH) study will test the safety, side effects, and antitumor activity of a drug called Emi-Le ((Emiltatug Ledadotin, formerly XMT-1660). A side effect is anything a drug does to the body besides treating the disease.

Participants in the study will have cancer that has come back after a period of time during which the cancer could not be detected (recurrent), spread in the body near where it started (advanced) or spread through the body (metastatic).

The study will have three parts. The first part called Dose Escalation, will find out how much Emi-Le should be given to participants. The second part called Dose Expansion, will use the dose found in the first part to find out how safe Emi-Le is and if it works to treat solid tumors. The third part, the Phase 2 part of the trial, called EMBLEM-1, will find out if Emi-Le works to treat aggressive Adenoid Cystic Carcinoma and continue to check how safe Emi-Le is.

Вмешательства

• Препарат Emi-Le
  Emi-Le will be administered through a vein in your arm or port catheter (intravenously)

Первичные конечные точки

• Frequency of adverse events that are considered dose-limiting toxicities (DLTs) and associated with Emi-Le during the first cycle of treatment (Dose Escalation) [Срок оценки: 17 months]
• Incidence of adverse events (Dose Escalation and Dose Expansion) [Срок оценки: 3 years]
• Objective Response Rate (ORR) (Dose Expansion and EMBLEM-1) [Срок оценки: approximately 3 years]

Вторичные конечные точки (8)

• Objective Response Rate (ORR) (Dose Escalation) [Срок оценки: Up to approximately 3 years]
• Duration of response (DOR) (Dose Escalation, Dose Expansion, and EMBLEM-1) [Срок оценки: Up to approximately 3 years]
• Maximum observed plasma concentration of Emi-Le and payload (Cmax) (Dose Escalation and Dose Expansion) [Срок оценки: Up to approximately 3 years]
• Area under the concentration-time curve of Emi-Le and payload (AUC) (Dose Escalation and Dose Expansion) [Срок оценки: Up to approximately 3 years]
• Antidrug antibodies (ADAs) and neutralizing antibodies (NAbs) (Dose Escalation, Dose Expansion, and EMBLEM-1) [Срок оценки: Up to approximately 3 years]
• Assess the overall survival (OS) of patients treated with Emi-Le (Dose Escalation, Dose Expansion, and EMBLEM-1) [Срок оценки: Up to approximately 3 years]
• Incidence of adverse events (EMBLEM-1) [Срок оценки: 3 years]
• Progression-free survival (PFS) (EMBLEM-1) [Срок оценки: Up to approximately 3 years]

Критерии участия

Критерии включения

• Recurrent or advanced solid tumor and has disease
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Participants in DES must have at least one measurable disease (target) lesion as defined by RECIST version 1.1.
• Tumor tissue, either archival or from a fresh tumor biopsy, available for testing or be willing to undergo a minimally invasive tumor biopsy to obtain tumor tissue for local testing, if not medically contraindicated, prior to Cycle 1 Day 1
• Brain magnetic resonance imaging (MRI) during the Screening period unless obtained within 30 days prior to Screening (based on standard clinical care), if they meet either of the following criteria:

• All participants with TNBC
• Participants with a history of brain metastases or with neurologic symptoms or signs suspicious for brain metastases.

Критерии исключения

• Prior treatment with an Antibody Drug Conjugate (ADC) containing an auristatin payload. Prior treatment with another ADC containing other payloads is allowed.
• Major surgery within 28 days of starting study treatment, systemic anticancer therapy within the time period of 28 days or 5 half-lives of the prior therapy before starting study treatment (14 days or 5 half-lives for small molecule targeted therapy), whichever is less, or palliative radiation therapy to the chest within 3 months of starting study treatment or to other anatomic sites within 14 days of starting study treatment.
• Diagnosis of additional malignancy that required active treatment (including surgery, systemic therapy, and radiation) within 2 years prior to screening, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix.
• Untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis.
• Prior B7-H4 targeted treatment.
• History of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver diseases.
• Current severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could increase the risk of serious adverse events (SAEs) or interfere with per-protocol evaluations, in the judgment of either the Sponsor or the Investigator.
• Clinically significant cardiovascular disease
• Active keratitis (inflammation of the cornea of the eye)

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 26 центров

• Mayo Clinic Comprehensive Cancer Center — Phoenix
• UC Irvine Health-Chao Family Comprehensive Cancer Center — Orange
• UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco
• UCLA David Geffen School of Medicine, Division of Hematology/Oncology — Santa Monica
• Mayo Clinic - Jacksonville — Jacksonville
• Florida Cancer Specialists — Sarasota
• Moffitt Cancer Center — Tampa
• Winship Cancer Institute, Emory University — Atlanta
• … и ещё 18 центров

Публикации

• Toader D, Fessler SP, Collins SD, Conlon PR, Bollu R, Catcott KC, Chin CN, Dirksen A, Du B, Duvall JR, Higgins S, Kozytska MV, Bellovoda K, Faircloth C, Lee D, Li F, Qin L, Routhier C, Shaw P, Stevenson CA, Wang J, Wongthida P, Ter-Ovanesyan E, Ditty E, Bradley SP, Xu L, Yin M, Yurkovetskiy AV, Mosher R, Damelin M, Lowinger TB. Discovery and Preclinical Characterization of XMT-1660, an Optimized B PMID 37294948

Идентификаторы

NCT: NCT05377996 · MER-XMT-1660-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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