Olaparib, durvalumab, and cyclophosphamide, and a prognostic blood signature in platinum-sensitive ovarian cancer: the randomized phase 2 SOLACE2 trial
- Chee Khoon Lee
- Apriliana E. R. Kartikasari
- Nirashaa T. Bound
- Katherine E. Francis
- Kristy Shield-Artin
- Justin Bedo
- Ksenija Nesic
- Katrina Diamante
- Rachel L. O’Connell
- Mutsa Madondo
- Momodou Cox
- Claire Davies
- Cyril Deceneux
- Georgia Goodchild
- Andrew Jarratt
- Emily Cassar
- Hina Amer
- U. G. Imalki U. Kariyawasam
- Yeh Chen Lee
- Janine Lombard
- Sally Baron-Hay
- Yoland Antill
- Catherine Shannon
- Sudarshan Selva-Nayagam
- Philip Beale
- Danka Zebic
- Sandy Simon
- Anneliese Linaker
- Michael A. Quinn
- Anthony T. Papenfuss
- Matthew J. Wakefield
- Cassandra J. Vandenberg
- Michael Friedlander
- Clare L. Scott
- Magdalena Plebanski
2025-11-05
SOLACE2 (ACTRN12618000686202) investigates whether 12-weeks of olaparib, or cyclophosphamide-olaparib priming, improves subsequent durvalumab-olaparib progression-free survival (PFS), and is superior to olaparib monotherapy without any priming, in platinum-sensitive recurrent ovarian cancer (n = 114). We also evaluate the utility of CUP-CC assay, an immune signature of C-C chemokine receptor type 4 up-regulation, chemokines, and cytokines. Priming with olaparib, or cyclophosphamide-olaparib, followed by durvalumab-olaparib, are both associated with longer PFS compared to olaparib monotherapy, but do not reach the pre-specified primary endpoint of 36-week trial threshold (PFS36). PFS36 rates are 47.4% (95% CI, 31.0-62.1; olaparib priming then olaparib-durvalumab), 48.7% (32.5-63.2; olaparib-cyclophosphamide then olaparib-durvalumab) and 35.1% (20.4-50.3; olaparib monotherapy). PFS is significantly longer for the homologous recombination deficient (N = 71) as compared to the proficient (HRP) (N = 29) subgroups (Hazard Ratio (HR) 0.55, 0.35-0.87). CUP-CC+ subgroup (N = 58) has a significantly longer PFS (HR 0.31, 0.19-0.49) than CUP-CC- (N = 46). Future studies should investigate whether CUP-CC has the potential to personalize poly (ADP-ribose) polymerase inhibitor therapies for patients who are BRCA wild-type, including HRP patients.