KEY TAKEAWAYS
- The MANTRA phase III trial aimed to compare the efficacy of milademetan and trabectedin in pretreated unresectable/metastatic DDLPS.
- The primary endpoint was PFS by BICR. Secondary endpoints were OS, ORR, DCR, DOR, PFS, and safety.
- The result demonstrated that the milademetan didn’t outperform trabectedin, but further testing in relevant populations is justified given manageable side effects.
For the study, researchers aimed to compare the efficacy of milademetan and trabectedin in pretreated unresectable/metastatic dedifferentiated liposarcomas(DDLPS).
Eligible patients (≥18 years) with unresectable/metastatic DDLPS±WD, having received at least one prior therapy (≥1 anthracycline regimen) and radiographic evidence of progression within six months were randomized (1:1) to receive milademetan or trabectedin until disease progression or intolerability. Milademetan was administered orally (260 mg orally QD d1–3 & d15–17 q28d), while trabectedin was given(1.5 mg/m2, 24-h iv infusion q3w). Tumor response assessments were conducted at weeks 8, 16, 24, and 32, followed by assessments every 12 weeks.
The primary endpoint was progression-free survival (PFS) evaluated by blinded independent central review (BICR), with secondary endpoints including overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), investigator-assessed PFS, and safety. The study sample size aimed to support a primary endpoint favoring milademetan (HR 0.5, 94% power, type I error 0.05).
With a median age of 64 years (range 20–82) and a predominantly white (69.7%) and male (56.6%) population, the study demonstrated a median follow-up of 2.1 months (range 0–13m). Median PFS by BICR was numerically higher for milademetan, though not statistically significant. While median OS was comparable between arms, as were ORR and DCR, the data were immature.
The most common all-grade and grade 3/4 treatment-emergent adverse events (TEAEs) for milademetan were reported. Notably, no Grade 5 events occurred with milademetan compared to five with trabectedin. Milademetan showed higher dose reductions due to TEAEs, but lower discontinuation rates compared to trabectedin.
The result demonstrated that the milademetan didn’t outperform trabectedin in dedifferentiated liposarcoma, but further testing in relevant populations is justified given manageable side effects.
Source: https://cslide.ctimeetingtech.com/asia2023/attendee/confcal/show/session/29
Clinical Trial: https://clinicaltrials.gov/study/NCT04979442
Chen TW, Sanfilippo R, Jones RL, Schuetze SM, Sebio Garcia A, Alvarez RM, Bui N, Ahn JH, Loong HHF, Yen CC, Hong JY, Kim HS, Patel S, Bryce RP, Xu F, Zhang B, Shah NV, Doebele RC, Schwartz G, Gounder M. Efficacy and safety findings from MANTRA: A global, randomized, multicenter, phase III study of the MDM2 inhibitor milademetan vs trabectedin in patients with dedifferentiated liposarcomas. Presented at ESMO ASIA 2023, Session-76MO. Taipei City, TW.
