EMBLEM-1

20 evidence topics · 8 sources

Objective

Registered objective of the phase 2 part

“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.” (opens the source at this quote in a new tab)

Sponsor-stated purpose of the phase 2 study

“These encouraging data at ASCO indicate strong promise to support a population distinctly in need of effective therapies and will help inform the pivotal Phase 2 study we will undertake in a larger set of participants.” (opens the source at this quote in a new tab)

Location and study date

Study dates and status: registry record for the full phase 1/2 protocol

Milestone	Registry record
Study start (actual)	“2022-08-15”
Primary completion (estimated)	“2027-02”
Study completion (estimated)	“2027-12”
Recruitment status	“Recruiting”
Last update posted	“2026-06-29”

Registered sites

“This study has 26 locations” (opens the source at this quote in a new tab)
“United States” (opens the source at this quote in a new tab)

Enrollment status of the phase 2 part

“The phase 2 EMBLEM-1 study (NCT05377996), a continuation of the phase 1 program, is enrolling patients with aggressive ACC and measurable disease per RECIST v1.1” (opens the source at this quote in a new tab)

EMBLEM-1 start date and site list specific to the phase 2 part

No evidence found.

Study design

Phase 1/2, single-group, open-label design with three parts

“A Phase 1/2, First-in-human, Multicenter Study of Emiltatug Ledadotin (Emi-Le) in Participants With Solid Tumors” (opens the source at this quote in a new tab)
“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.” (opens the source at this quote in a new tab)

Design feature	Registry record
Primary purpose	“Treatment”
Allocation	“N/A”
Interventional model	“Single Group Assignment”
Masking	“None (Open Label)”

Planned registrational pathway

“The objective of the Phase 1b study is to define an optimized dose and to define clinical activity in one or more histologically defined tumor types for a potential single-arm registrational trial for accelerated approval or randomized trial.” (opens the source at this quote in a new tab)

Contingent value right milestone tied to a registrational ACC-1 trial

“$4.00 per CVR, payable upon occurrence of the first dosing of the first participant in a Registrational Clinical Trial (as defined in the CVR Agreement) of Emi-Le for adenoid cystic carcinoma type 1 (“ACC-1”) on or before December 31, 2027;” (opens the source at this quote in a new tab)

Tissue submission for biomarker testing

“Tissue is submitted for B7-H4 testing and molecular profiling.” (opens the source at this quote in a new tab)

Eligibility criteria

Aggressive ACC definition for EMBLEM-1

“The phase 2 EMBLEM-1 study (NCT05377996), a continuation of the phase 1 program, is enrolling patients with aggressive ACC and measurable disease per RECIST v1.1, with the phenotype confirmed by both histopathologic criteria (solid/basaloid histology or HGT) and clinical phenotype (progression within 3 years or extrapulmonary metastasis).” (opens the source at this quote in a new tab)

Key inclusion criteria: registry record for all study parts

Criterion	Quoted registry text
Disease	“Recurrent or advanced solid tumor and has disease”
Performance status	“Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1”
Tumor tissue	“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”
Age	“18 Years and older”

Key exclusion criteria: registry record for all study parts

“Prior treatment with an Antibody Drug Conjugate (ADC) containing an auristatin payload. Prior treatment with another ADC containing other payloads is allowed.” (opens the source at this quote in a new tab)
“Prior B7-H4 targeted treatment.” (opens the source at this quote in a new tab)
“Untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis.” (opens the source at this quote in a new tab)
“History of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver diseases.” (opens the source at this quote in a new tab)
“Clinically significant cardiovascular disease” (opens the source at this quote in a new tab)
“Active keratitis (inflammation of the cornea of the eye)” (opens the source at this quote in a new tab)

ACC-specific eligibility criteria in the registry record

No evidence found.

Treatment

EMBLEM-1 dosing regimen

“The dosing regimen is emiltatug ledadotin 80 mg/m² (capped at 160 mg) Q4W, with ORR as the primary end point and DOR, DCR, PFS, overall survival, and safety as secondary end points.” (opens the source at this quote in a new tab)

Registered intervention

“Single arm Emi-Le alone (monotherapy)” (opens the source at this quote in a new tab)
“Emi-Le will be administered through a vein in your arm or port catheter (intravenously)” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using RECIST v1.1 objective response rate as the primary endpoint

Registered primary outcome for EMBLEM-1

Outcome measure	Description	Time frame
“Objective Response Rate (ORR) (Dose Expansion and EMBLEM-1)”	“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”	“approximately 3 years”

Registered secondary outcomes for EMBLEM-1

Outcome measure	Description	Time frame
“Duration of response (DOR) (Dose Escalation, Dose Expansion, and EMBLEM-1)”	“The time from when response criteria are first met until disease progression or death in participants who achieve a complete or partial response”	“Up to approximately 3 years”
“Progression-free survival (PFS) (EMBLEM-1)”	“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”	“Up to approximately 3 years”
“Assess the overall survival (OS) of patients treated with Emi-Le (Dose Escalation, Dose Expansion, and EMBLEM-1)”	“The time from the date of first dose of study treatment to the date of death due to any cause”	“Up to approximately 3 years”
“Incidence of adverse events (EMBLEM-1)”	“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”	“3 years”
“Antidrug antibodies (ADAs) and neutralizing antibodies (NAbs) (Dose Escalation, Dose Expansion, and EMBLEM-1)”	“Assess the development of ADAs and NAbs to Emi-Le”	“Up to approximately 3 years”

Regulatory basis for ORR in single-arm studies

“When defined in this manner, ORR is a direct measure of a drug antitumor activity, which can be evaluated in a single-arm study.” (opens the source at this quote in a new tab)
“The significance of ORR is assessed by its magnitude and duration, and the percentage of CRs.” (opens the source at this quote in a new tab)
“In settings where there is no available therapy and where major tumor regressions can be presumed to be attributed to the tested drug, the FDA has sometimes accepted ORR and response duration observed in single-arm studies as substantial evidence supporting accelerated approval.” (opens the source at this quote in a new tab)
“Single-arm trials do not adequately characterize time-to-event endpoints such as overall survival, DFS (and EFS), TTP, or PFS.” (opens the source at this quote in a new tab)

Absence of approved therapy and historical outcomes in aggressive ACC

“About 40% of patients (pts) have an aggressive form of ACC (referred to as ACC-I; Ferrarotto et al., Clin Cancer Res 2021) characterized by solid/basaloid or high-grade transformation histology and poor prognosis with median progression-free survival (PFS) of 2–3 months and median overall survival (OS) of approximately 3 years. There are no approved systemic therapies for recurrent or metastatic ACC.” (opens the source at this quote in a new tab)

Sponsor-stated rationale for selecting ORR in EMBLEM-1

No evidence found.

Statistical analysis description

Number of participants (Planned and analyzed)

Planned enrollment: registry record for all study parts

Enrollment type	Participants
Estimated	“360”

Planned enrollment specific to EMBLEM-1

No evidence found.

Description of analysis sets

No evidence found.

Results

Participant disposition

No evidence found.

Baseline characteristics

No evidence found.

Efficacy results

No evidence found.

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

No evidence found.

Study limitations

Summary

EMBLEM-1 is the phase 2 part of the NCT05377996 protocol and had reported no results as of the June 29, 2026 registry update. Public information on the design comes from the registry record, which covers all three study parts, and from a conference report of the ASCO 2026 presentation. The planned EMBLEM-1 sample size, the prespecified ORR threshold, the use of blinded independent central review, and the statistical analysis plan are not public; the registry lists investigator-assessed ORR and an estimated enrollment of 360 participants for the entire phase 1/2 study. The single-arm design without a comparator means time-to-event outcomes such as PFS and OS cannot be attributed to treatment, a limitation noted in FDA endpoint guidance. Eligibility requires both a histopathologic phenotype (solid/basaloid histology or high-grade transformation) and a clinical phenotype, which matches the population in the May 2026 FDA breakthrough therapy designation, so results would not apply to non-aggressive ACC. The registry exclusion criteria remove participants with prior auristatin-based or B7-H4-targeted therapy, untreated CNS metastases, clinically significant liver or cardiovascular disease, and active keratitis.