Trabectedin–durvalumab combo shows antitumour activity in refractory ovarian carcinoma
10 May 2022
Combination treatment with trabectedin and durvalumab appears to be promising in the treatment of patients with platinum-refractory ovarian carcinoma, shrinking tumour while having a manageable side effect profile, according to data from the phase Ib TRAMUNE trial.
Already, trabectedin had shown synergy with immune checkpoint inhibitors in preclinical models. TRAMUNE examined the combination of trabectedin with durvalumab through a dose escalation phase (n=9) and two expansion cohorts (soft tissue sarcoma [STS], n=16; ovarian carcinoma, n=15). The population comprised 40 patients in total.
Researchers administered trabectedin at three dose levels (1 mg/m2, 1.2 mg/m2, and 1.5 mg/m2) on day 1, in combination with durvalumab at 1,120 mg on day 2, every 3 weeks.
The most common toxicities documented were grade 1–2 fatigue, nausea, neutropenia, and alanine/aspartate aminotransferase elevation. There was one patient who experienced a dose-limiting toxicity at dose level 2. The researchers selected trabectedin at 1.2 mg/m2 as the recommended phase II dose.
In terms of efficacy, 43 percent of patients in the STS cohort experienced tumour shrinkage. The corresponding objective response rate (ORR) was 7 percent (95 percent confidence interval [CI], 0.2–33.9), while the 6-month progression-free rate (PFR) was 28.6 percent (95 percent CI, 8.4–58.1).
In the ovarian carcinoma cohort, tumour shrinkage occurred in 43 percent of patients. The corresponding ORR was 21.4 percent (95 percent CI, 4.7–50.8), and the 6-month PFR was 42.9 percent (95 percent CI, 17.7–71.1).
Baseline levels of programmed death-ligand 1 expression and CD8-positive T-cell infiltrates were associated with progression-free survival among patients with ovarian carcinoma.