Abstract
1115P NRG GY012: A randomized phase II study comparing single-agent cediranib with olaparib/durvalumab, cediranib/durvalumab, and olaparib/capivasertib in women with recurrent, persistent or metastatic endometrial cancer
Annals of oncology, Vol.36(Suppl 2), pp.S742-S742
09/2025
DOI: 10.1016/j.annonc.2025.08.1752
Abstract
Background
NRG-GY012 is a randomized platform trial investigating drug combinations targeting angiogenesis, immune-mediated therapy, and DNA repair compared to the reference arm of cediranib (C ) alone in patients with pre-treated metastatic endometrial cancer (EC). Here we report results of the second cohort of sub studies which explored the combination of: olaparib (O) and the AKT inhibitor capivasertib (CA); O with durvalumab (D) and C with D (NCT03660826).
Methods
Eligible patients (pts) had at least 1 prior line of chemotherapy (no more than 2) with prior endocrine and immunotherapy (prior lenvatinib/pembrolizumab excluded) allowed, ECOG 0-1. NRG GY012 was a multicenter randomized study with pts randomized 1:1:1:1 to the reference arm C 30 mg PO Daily or to one of 3 experimental arms: O 300 mg PO BID and CA 400 mg 4 day on/3 off schedule; O 300 mg PO BID and D 1500mg q28 days; or the combination of C 20 mg PO Daily 5 days on/2 days and D 1500mg q28. Archival formalin fixed tissue and blood samples were collected.
Results
Between Aug 2021 and Feb 2022, 168 pts were enrolled and treated: 153 PFS events were observed across the four treatment arms (37 in cediranib, 38 in O+CA, 41 in O+D, and 37 in C+D). Median age was 67 years (range 30-85); 66(39%) were serous, 92( 55%) were endometrioid, 10 (6%) were other. Molecular subtyping will be available. 31% of patients had received prior immunotherapy, balanced across study arms. Median PFS per Kaplan Meier method was was: 4.1mo for C; 3.7mo for O+D, 5.6mo for O+CA, and 6.0mo for D+C. The one-sided p value startified log rank test comparing O+D vs. C was 0.36: HR 0.92(0.58-1.46 95%CI) and O+CA vs. C 0.62: was HR 1.06 (0.67-1.7 95%CI) and D+C vs. C 0.14: was HR 0.78(0.49-1.25 95% CI). Median OS from randomization: 16.6 months for C; 16.9 months for O+CA, 14.0 months for O+D, and 22.6 months for C+D. No new safety signals were reported.
Conclusions
The combinations of O+D, O+CA and C+D did not meet prespecified endpoints for significance in an unselected population. Further evaluation of molecular subgroups and prior immunotherapy treatment is necessary to determine if there are any signals warranting future investigation.
Details
- Title: Subtitle
- 1115P NRG GY012: A randomized phase II study comparing single-agent cediranib with olaparib/durvalumab, cediranib/durvalumab, and olaparib/capivasertib in women with recurrent, persistent or metastatic endometrial cancer
- Creators
- B. Rimmel - Cedars-Sinai Medical CenterD. Bender - University of IowaD. Enserro - NRG OncologyS. Westin - The University of Texas MD Anderson Cancer CenterM.A. Powell - Washington University in St. Louis School of MedicineL. Holman - University of Oklahoma Health Sciences CenterR.G. Moore - University of RochesterF. Backes - The Ohio State UniversityF.B. Musa - Swedish Cancer InstituteP. DiSilvestro - Brown UniversityN. Godbee - City Of Hope National Medical CenterS.E. Gill - Oncology, Nancy N, JC Lewis Cancer, Research Pavilion, Savannah, United States of AmericaC.A. Leath - University of Alabama at BirminghamE. Barber - Robert H. Lurie Comprehensive Cancer Center of Northwestern UniversityL. Beffa - Cleveland ClinicC. Aghajanian - Memorial Sloan Kettering Cancer CenterH. Mackay - University of Toronto
- Resource Type
- Abstract
- Publication Details
- Annals of oncology, Vol.36(Suppl 2), pp.S742-S742
- DOI
- 10.1016/j.annonc.2025.08.1752
- ISSN
- 0923-7534
- eISSN
- 1569-8041
- Publisher
- Elsevier Ltd
- Grant note
- NRG Oncology
NRG Oncology.
- Language
- English
- Date published
- 09/2025
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9985035032502771
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