A phase 2, randomized, double-blind, placebo- controlled study of chemo-immunotherapy combination using motolimod with pegylated liposomal doxorubicin in recurrent or persistent ovarian cancer: a Gynecologic Oncology Group partners study
B.J. Monk, M.F. Brady, C. Aghajanian, H.A. Lankes, T. Rizack, J. Leach, J.M. Fowler, R. Higgins, P. Hanjani, M. Morgan, R. Edwards, W. Bradley, T. Kolevska, P. Foukas, E.M. Swisher, K.S. Anderson, R. Gottardo, J.K. Bryan, M. Newkirk, K.L. Manjarrez, R.S. Mannel, R.M. Hershberg, G. Coukos
Abstract
A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death.
Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo. Randomization was stratified by platinum-free interval (≤6 versus >6-12 months) and gynecologic oncology group (GOG) performance status (0 versus 1). Treatment cycles were repeated every 28 days until disease progression.
The addition of motolimod to PLD did not significantly improve overall survival (OS; log rank one-sided P = 0.923, HR = 1.22) or progression-free survival (PFS; log rank one-sided P = 0.943, HR = 1.21). The combination was well tolerated, with no synergistic or unexpected serious toxicity. Most patients experienced adverse events of fatigue, anemia, nausea, decreased white blood cells, and constipation. In pre-specified subgroup analyses, motolimod-treated patients who experienced injection site reactions (ISR) had a lower risk of death compared with those who did not experience ISR. Additionally, pre-treatment in vitro responses of immune biomarkers to TLR8 stimulation predicted OS outcomes in patients receiving motolimod on study. Immune score (tumor infiltrating lymphocytes; TIL), TLR8 single-nucleotide polymorphisms, mutational status in BRCA and other DNA repair genes, and autoantibody biomarkers did not correlate with OS or PFS.
The addition of motolimod to PLD did not improve clinical outcomes compared with placebo. However, subset analyses identified statistically significant differences in the OS of motolimod-treated patients on the basis of ISR and in vitro immune responses. Collectively, these data may provide important clues for identifying patients for treatment with immunomodulatory agents in novel combinations and/or delivery approaches.
Clinicaltrials.gov, NCT 01666444.
Practitioners (doctors, other healthcare professionals)
1
20%
Scientists
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Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 13. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 April 2026.
All research outputs
#3,441,194
of 31,634,113 outputs
Outputs from Annals of Oncology
#2,151
of 9,710 outputs
Outputs of similar age
#50,415
of 338,683 outputs
Outputs of similar age from Annals of Oncology
#52
of 125 outputs
Altmetric has tracked 31,634,113 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 9,710 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.0. This one has done well, scoring higher than 77% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 338,683 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 85% of its contemporaries.
We're also able to compare this research output to 125 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 58% of its contemporaries.
