Adenoid Cystic Carcinoma, Breast Cancer, Endometrial Cancer, Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer, Triple Negative Breast Cancer
Conditions
Brief summary
A Study of Emi-Le in Participants with Solid Tumors
Detailed description
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.
Interventions
DRUGEmi-Le
Emi-Le will be administered through a vein in your arm or port catheter (intravenously)
Sponsors
Day One Biopharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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: 1. All participants with TNBC 2. Participants with a history of brain metastases or with neurologic symptoms or signs suspicious for brain metastases.
Exclusion criteria
* 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of adverse events that are considered dose-limiting toxicities (DLTs) and associated with Emi-Le during the first cycle of treatment (Dose Escalation) | 17 months | Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of Emi-Le |
| Incidence of adverse events (Dose Escalation and Dose Expansion) | 3 years | Assess the safety and tolerability of Emi-Le by determining the number of patients with adverse events from date of first dose to 60 days post last dose |
| Objective Response Rate (ORR) (Dose Expansion and EMBLEM-1) | approximately 3 years | The percentage of patients with a best overall response of complete or partial response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) (Dose Escalation) | Up to approximately 3 years | The percentage of patients with a best overall response of complete or partial response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| Duration of response (DOR) (Dose Escalation, Dose Expansion, and EMBLEM-1) | Up to approximately 3 years | The time from when response criteria are first met until disease progression or death in participants who achieve a complete or partial response |
| Maximum observed plasma concentration of Emi-Le and payload (Cmax) (Dose Escalation and Dose Expansion) | Up to approximately 3 years | Cmax is the maximum concentration determined from the measured concentrations in plasma |
| Area under the concentration-time curve of Emi-Le and payload (AUC) (Dose Escalation and Dose Expansion) | Up to approximately 3 years | Area under the concentration-time curve for the last measurable concentration (AUC0-last) will be assessed as data permit |
| Antidrug antibodies (ADAs) and neutralizing antibodies (NAbs) (Dose Escalation, Dose Expansion, and EMBLEM-1) | Up to approximately 3 years | Assess the development of ADAs and NAbs to Emi-Le |
| Assess the overall survival (OS) of patients treated with Emi-Le (Dose Escalation, Dose Expansion, and EMBLEM-1) | Up to approximately 3 years | The time from the date of first dose of study treatment to the date of death due to any cause |
| Incidence of adverse events (EMBLEM-1) | 3 years | Assess the safety and tolerability of Emi-Le by determining the number of patients with adverse events from date of first dose to 60 days post last dose |
| Progression-free survival (PFS) (EMBLEM-1) | Up to approximately 3 years | The time from the date of first dose of study treatment until the first date at which disease progression is objectively documented or date of death due to any cause, whichever occurs first |
Countries
United States
Contacts
CONTACTDay One Clinical Trials Information
STUDY_DIRECTORRobert Burger, MD
Day One Biopharmaceuticals, Inc.
Outcome results
None listed