Sapanisertib Plus Weekly Chemo Improves PFS in Platinum-Resistant Ovarian Cancer

In patients with advanced/recurrent platinum-resistant ovarian cancer (PROC), progression-free survival (PFS) improved following treatment with sapanisertib (TAK228) added to weekly paclitaxel chemotherapy, according to findings from the phase 2 DICE trial (NCT03648489) presented at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.¹

The findings were reported by Dr Jonathan Krell, clinical associate professor at Imperial College in London, United Kingdom. The principal finding was that the addition of sapanisertib to weekly paclitaxel improved PFS at the 10% significance level (HR, 0.66; 90% CI, 0.45–0.96, P =.07), equating to a 34% reduction in the risk of death compared with weekly paclitaxel alone.

“If we look at the Kaplan-Meier curves, we can see that the 2 arms separate around the median of just over 5 months, suggesting that there are a significant proportion of patients who benefit from the addition of sapanisertib compared [with] others,” explained Krell during the presentation.¹

In terms of toxicities, the combination was well tolerated by patients. The frequency of grade 3/4 adverse events (AEs) was slightly higher in the combination arm compared with the chemotherapy-only arm (7% vs 6.6%). Further, a surprising finding, according to Krell, was that the combination arm experienced significantly more serious AEs compared with the chemotherapy-only arm, including gastrointestinal disorders (11.4% vs 0%) and rash (2.9% vs 0%).

What was the DICE trial’s design and treatment protocol?

The DICE trial was an international, multicenter, randomized phase 2 study comparing the efficacy of sapanisertib plus weekly paclitaxel with weekly paclitaxel alone.^2,3 The study’s primary end point was PFS per RECIST v1.1/GCIG CA125 criteria; secondary end points included overall survival (OS), response rate (RR), and safety. Moreover, a corresponding translational analysis aimed to assess correlation of PTEN levels with outcome and analyze novel predictive biomarkers.

The study recruited 134 adult women from the United Kingdom and Germany who have platinum-resistant/refractory, high-grade epithelial ovarian cancer, including the histological subtypes of carcinosarcoma, endometrioid, clear cell carcinoma, or high-grade serous ovarian carcinoma. Besides the disease criteria, patients were included if they had at least 1 prior line of chemotherapy and a fasting serum glucose of ≤7 mmol/L.

Patients were randomized 1:1 to receive either weekly paclitaxel alone (n = 66) or weekly paclitaxel plus sapanisertib (n = 68). The treatment regimen for all patients involved receiving 80 mg/m² of intravenous paclitaxel on days 1, 8, and 15 for 28-day cycles; in the combination arm, patients also received a 4-mg dosage of sapanisertib on days 2 to 4, 9 to 11, 16 to 18, and 23 to 25 throughout the 28-day cycles. Treatment was stopped upon disease progression, unacceptable AEs, or if either the investigator or patient initiated discontinuation.

What are the next steps in research?

In his conclusion, Krell stated that secondary end point analysis results for RR and OS are forthcoming and expected within the week following the 2025 ESMO Congress and that translational research is ongoing to identify predictive biomarkers. Ultimately, these efficacy and safety findings provide a strong rationale for advancing the combination to a larger phase 3 trial to further evaluate efficacy.

“We feel these results support the development of a phase 3 trial of sapanisertib with weekly paclitaxel in PROC,” Krell concluded.

DISCLOSURES: Krell declared receipt of honoraria from AstraZeneca, GSK, and MSD, institutional research funding from Takeda, 4D Pharma, and Curesponse LTD, institutional research collaboration with Faeth Therapeutics, and a role as medical director at My Doctor’s Recipe.

REFERENCES:

1. Krell, J. DICE trial: An international multi-centre randomised phase II study to assess the efficacy of TAK228 in combination with intravenous weekly paclitaxel compared with weekly paclitaxel alone in women with advanced/recurrent epithelial ovarian or fallopian tube cancer. Presented at: ESMO 2025 Congress; October 17–21, 2025; Berlin, Germany. Abstract LBA46.

2. Dual mTorc Inhibition in advanCed/​Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer (of Clear Cell, Endometrioid and High Grade Serous Type, and Carcinosarcoma) (DICE). ClinicalTrials.gov. Updated September 20, 2024. Accessed October 21, 2025. https://clinicaltrials.gov/study/NCT03648489

3. Fiorentino F, Krell J, de la Rosa CN, Webber L. DICE: Dual mTorc Inhibition in advanCed/recurrent Epithelial ovarian cancer resistant to standard treatment-a study protocol for a randomised trial investigating a novel therapy called TAK228. Trials. 2022 Apr 5;23(1):261. doi: 10.1186/s13063-022-06201-3. PMID: 35382842; PMCID: PMC8980506.