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Emiltatug ledadotin (Emi-Le)

Adenoid cystic carcinoma with solid histology or high-grade transformation

Also known as XMT-1660
Manufacturer
Servier
Regulatory submission
Not announced
Launch
Not announced
Last updated
125 sources

Product information and disease descriptionProduct descriptionProduct information

Contraindications/Warnings/Precautions/Adverse effects

10 evidence topics · 8 sources

Warnings and precautions
Summary: safety profile in the phase 1 trial

No prescribing information, boxed warning, contraindication, or risk evaluation and mitigation strategy exists because emiltatug ledadotin is investigational. In the ASCO 2026 abstract safety set (221 participants, data cutoff 1 October 2025), the most common treatment-related adverse events were proteinuria (49.8%), transient AST increase (49.3%), and fatigue (41.2%); grade 3 AST increase and grade 3 proteinuria each occurred in 17.6%, and 3.6% discontinued treatment because of treatment-related adverse events. The oral presentation reported 180 participants with transient AST increase (56%), proteinuria (54%), fatigue (42%), and nausea (33%), with no grade 4 or 5 events. Among 48 participants with ACC, treatment-related adverse events led to dose reduction in 45.8% and dose delay in 56.3%, and proteinuria (characterized on biopsy as glomerular podocytopathy) was the leading cause of dose modification. After a protocol amendment that added monitoring and renal-protective medications, proteinuria-related dose reductions decreased from 38.9% to 20% and delays from 50.0% to 6.7% among participants with ACC. Neutropenia (2.2%), keratitis (3.9%), and peripheral neuropathy (2.8%) were reported at low rates. Severe adverse events observed with UpRi, an earlier Mersana ADC that used the same auristatin payload, included hemorrhage, proteinuria, pneumonitis, and death.

Prescribing information, boxed warnings, contraindications, and REMS

Not applicable.

Treatment-related adverse events: all enrolled participants, October 2025 data cutoff

“As of October 1, 2025, 221 pts were dosed.” (opens the source at this quote in a new tab)

“For the safety set of 221 pts, Emi-Le was well tolerated with no new safety signals identified. The most common treatment-related adverse events (TRAEs) were proteinuria (49.8%), transient AST increase (49.3%), and fatigue (41.2%). The only Grade 3 TRAEs in ≥10% of pts were transient AST increase (17.6%) and proteinuria (17.6%). TRAEs leading to treatment discontinuation occurred in 3.6% of pts. No treatment-related deaths were reported.” (opens the source at this quote in a new tab)

Treatment-related adverse events: ASCO 2026 oral presentation

“The most common TRAEs were transient AST increase (56%) generally asymptomatic and reversible proteinuria (54%), predominantly low-grade fatigue (42%) and nausea (33%).” (opens the source at this quote in a new tab)

“The only Grade 3 TRAEs in ≥10% of pts were transient AST increase (20%) and proteinuria (23%). No Grade 4 or 5 TRAEs reported.” (opens the source at this quote in a new tab)

“TRAEs leading to treatment discontinuation occurred in 3.9% of patients and no treatment-related deaths were reported.” (opens the source at this quote in a new tab)

“Any-grade treatment-related adverse effects (TRAEs) occurred in 88.9% of all patients and 100% of those with ACC, and grade 3 TRAEs occurred in 51.1% and 79.2%, respectively. There were no grade 4 or 5 TRAEs and no treatment-related deaths.” (opens the source at this quote in a new tab)

Treatment-related adverse events: earlier data cutoffs

“As of the December 13, 2024 data cut date, the following TRAEs of any grade were observed in 10% or more of patients across the entire population or in one of three dose groups: AST increase, proteinuria, nausea, fatigue, pyrexia, decreased appetite, diarrhea, ALT increase, anemia, ALP increase, decreased platelet count, vomiting, arthralgia, constipation, hypophosphatemia, increased amylase and headache.” (opens the source at this quote in a new tab)

“As of the March 8, 2025 data cut date, the most common TRAEs of any grade across the entire patient population were transient aspartate aminotransferase, or AST, increase (44% of patients), generally asymptomatic and reversible proteinuria (40%), low-grade fatigue (33%) and generally low-grade nausea (31%). The only Grade 3 TRAEs in ≥5% or more of all patients were AST increase (17%), proteinuria (14%) and anemia (6%).” (opens the source at this quote in a new tab)

Proteinuria: characterization, dose modification, and mitigation in participants with ACC

“TRAEs led to discontinuation in only 1 patient (2.1%), dose reduction in 45.8%, and dose delay in 56.3% of patients. Asymptomatic proteinuria, characterized on post hoc biopsy as glomerular podocytopathy without acute renal vascular injury, represented the leading cause of dose modification. After a protocol amendment introduced an updated monitoring and management plan, including renal-protective medications, proteinuria-related dose reductions decreased from 38.9% to 20% and delays from 50.0% to 6.7% among patients with ACC.” (opens the source at this quote in a new tab)

Proteinuria at high doses: effect on response confirmation

“At these high dose levels, objective responses in multiple evaluable patients with B7-H4 high tumors were not confirmed after protocol-mandated dose delays for proteinuria. Mersana is implementing proteinuria mitigation efforts and continues to explore higher doses in dose escalation and backfill cohorts to identify a second dose for the expansion portion of the trial.” (opens the source at this quote in a new tab)

“Across the entire enrolled patient population, TRAEs leading to discontinuation, dose reduction and dose delay were observed in 2.3%, 9.2% and 12.3% of patients, respectively.” (opens the source at this quote in a new tab)

Aspartate aminotransferase elevation

“The most common TRAEs were transient aspartate aminotransferase elevations, which resolved to baseline or grade 1 by the subsequent dose, with no hepatic failure or Hy's law observed; asymptomatic and reversible proteinuria; and predominantly low-grade fatigue and nausea.” (opens the source at this quote in a new tab)

Hematologic, neurologic, ocular, and pulmonary toxicities associated with other ADCs

“No observed dose-limiting treatment-related neutropenia, neuropathy, ocular toxicity, interstitial lung disease or thrombocytopenia.” (opens the source at this quote in a new tab)

“There was no alopecia and no interstitial lung disease or pneumonitis, and rates of cytopenias, peripheral neuropathy, keratitis, and ocular toxicity were low relative to other ADCs, according to Hanna. Neutropenia, keratitis, and neuropathy occurred in 2.2%, 3.9%, and 2.8% of all patients, respectively.” (opens the source at this quote in a new tab)

Class and platform risks: severe adverse events with other ADCs using the same auristatin payload

“Patients in our clinical trials of UpRi, for which we discontinued development in 2023 and which was developed using our Dolaflexin platform, experienced severe TRAEs including, without limitation, death, hemorrhage, aspartate aminotransferase, or AST, elevation, nausea, platelet count decrease (including thrombocytopenia), fatigue, anemia, pyrexia, alanine aminotransferase, or ALT, elevation, blood alkaline phosphatase/lactate dehydrogenase, or ALP/LDH, increase, proteinuria, vomiting, asthenia, diarrhea, headache, peripheral neuropathy, neutropenia and pneumonitis.” (opens the source at this quote in a new tab)

“We are currently conducting a Phase 1 clinical trial of Emi-Le, which was developed using our Dolasynthen platform and utilizes the same auristatin payload as UpRi and XMT-1592.” (opens the source at this quote in a new tab)

Nonclinical toxicology

“Moreover, the ADCs exhibited comparable safety profiles which were consistent with AF-HPA–based ADCs (27).” (opens the source at this quote in a new tab)