Summary: dose levels and dose selected for phase 2

Dose escalation evaluated 7.2 to 115 mg/m2 per cycle on three schedules (every 4 weeks, every 3 weeks, and days 1 and 8 of a 28-day cycle). Participants with ACC received 57.4 to 89 mg/m2 per cycle every 3 or 4 weeks. The first expansion dose (Dose A) was 67.4 mg/m2 every 4 weeks, selected from the intermediate dose range (38.1 to 67.4 mg/m2); at doses at or above 76.2 mg/m2, proteinuria-related dose delays prevented confirmation of some responses. A second expansion dose (Dose B) used 44.5 mg/m2 on days 1 and 8 of the first 4-week cycle followed by 80 mg/m2 every 4 weeks, and an 80 mg/m2 every-4-week cohort was also evaluated. The dose selected for the EMBLEM-1 phase 2 part is 80 mg/m2 every 4 weeks, capped at 160 mg. No labeled dose, dose-adjustment table, or recommended dose for any approved use exists.

Dose escalation: dose range, schedules, and dose groups

“The dose escalation portion of the clinical trial evaluated doses ranging from 7.2 mg/m2 to 115 mg/m2, as well as the following dosing schedules: Q4W; once every three weeks; and on days 1 and 8 of a 28-day cycle.” (opens the source at this quote in a new tab)
“We analyzed initial trial data as of the data cut date across the entire trial population and in three dose groups: those in a “Subtherapeutic Dose Range” from 7.2 to 28.7 mg/m2 per cycle, an “Intermediate Dose Range” from 38.1 to 67.4 mg/m2 per cycle and a “High Dose Range” at or above 76.2 mg/m2 per cycle.” (opens the source at this quote in a new tab)

Phase 1: doses received by participants with ACC

“Pts with ACC received Emi-Le at doses of 57.4–89 mg/m2 IV per Q3W or Q4W cycle.” (opens the source at this quote in a new tab)

Initial expansion dose: 67.4 mg/m2 every 4 weeks

“Based on these encouraging Emi-Le data at intermediate doses, Mersana has advanced a dose of 67.4 mg/m2 every four weeks (Q4W) into an expansion cohort in patients with TNBC who have received one to four prior treatment lines, including at least one prior topo-1 ADC.” (opens the source at this quote in a new tab)

“All 4 pts with high B7-H4 expression treated at the initial EXP dose of 67.4mg/m2 Q4W had tumor reductions and were on treatment with durations of ≥16 weeks as of data cutoff.” (opens the source at this quote in a new tab)

Second expansion dose: split-dose lead-in followed by 80 mg/m2 every 4 weeks

“The second dose expansion cohort is the “Dose B” cohort, in which patients are receiving 80 mg/m2 of Emi-Le Q4W following a loading dose of 44.5 mg/m2 of Emi-Le on days 1 and 8 of the first four-week cycle.” (opens the source at this quote in a new tab)

“The expansion phase, which is enrolling patients with TNBC and ACC-I, evaluates 67.4 mg/m² every 4 weeks (Q4W), a 44.5-mg/m² split-dose lead-in followed by 80 mg/m² Q4W, and 80 mg/m² Q4W.” (opens the source at this quote in a new tab)

Dose selected for EMBLEM-1: 80 mg/m2 every 4 weeks, capped at 160 mg

“We landed on 80 mg/m2 monthly as the preferred dose” (opens the source at this quote in a new tab)
“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)

Dose modification guidance and dosing in organ impairment

No evidence found.

Emiltatug ledadotin (Emi-Le)

Dosage