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A Phase IB open-label, dose-escalation study of NUC 1031 in combination with carboplatin for recurrent ovarian cancer
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dc.contributor.author | Kazmi, F | |
dc.contributor.author | Nicum, S | |
dc.contributor.author | Roux, R | |
dc.contributor.author | Spiers, L | |
dc.contributor.author | Gnanaranjan, C | |
dc.contributor.author | Sukumaran, A | |
dc.contributor.author | Gabra, H | |
dc.contributor.author | Ghazaly Kerwash, Essam | |
dc.contributor.author | McCracken, N | |
dc.contributor.author | Harrison, David James | |
dc.contributor.author | Blagden, S P | |
dc.date.accessioned | 2022-03-19T00:40:09Z | |
dc.date.available | 2022-03-19T00:40:09Z | |
dc.date.issued | 2021-03-19 | |
dc.identifier | 273354114 | |
dc.identifier | b52d7b5f-60b6-4c00-9e49-61e2db5c8ea6 | |
dc.identifier | 85107005103 | |
dc.identifier | 000657419800010 | |
dc.identifier.citation | Kazmi , F , Nicum , S , Roux , R , Spiers , L , Gnanaranjan , C , Sukumaran , A , Gabra , H , Ghazaly Kerwash , E , McCracken , N , Harrison , D J & Blagden , S P 2021 , ' A Phase IB open-label, dose-escalation study of NUC 1031 in combination with carboplatin for recurrent ovarian cancer ' , Clinical Cancer Research . https://doi.org/10.1158/1078-0432.CCR-20-4403 | en |
dc.identifier.issn | 1078-0432 | |
dc.identifier.other | ORCID: /0000-0001-9041-9988/work/91340920 | |
dc.identifier.uri | https://hdl.handle.net/10023/25069 | |
dc.description | Funding: The study was funded and the investigational drug NUC-1031 was supplied by NuCana plc. | en |
dc.description.abstract | Purpose: NUC-1031 is a first-in-class ProTide modification of gemcitabine. In PRO-002, NUC‑1031 was combined with carboplatin in recurrent ovarian cancer (OC). Experimental Design: NUC-1031 was administered on days 1 & 8 with carboplatin on day 1 every 3 weeks for up to 6 cycles. Four dose cohorts of NUC-1031 (500, 625 and 750 mg/m2) with carboplatin (AUC4 or 5) were investigated. Primary endpoint was RP2CD. Secondary endpoints included safety, investigator-assessed objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS) and pharmacokinetics (PK). Results: 25 women with recurrent OC, a mean of 3.8 prior lines of chemotherapy and a median platinum-free interval (PFI) of 5 months (range: 7 - 451 days) were enrolled, 15/25 (60%) platinum-resistant; 9 (36%) partially platinum-sensitive and 1 (4%) platinum-sensitive. Of the 23 response-evaluable: there was 1 confirmed complete response (CR, 4%), 5 partial responses (PR, 17%) and 8 (35%) stable disease (SD). The ORR was 26% and CBR was 74% across all doses and 100% in the RP2CD cohort. Median PFS was 27.1 weeks. NUC-1031 was stable in the plasma and rapidly generated high intracellular dFdCTP levels that were unaffected by carboplatin. Conclusions: NUC-1031 combined with carboplatin is well tolerated in recurrent OC. Highest efficacy was observed at the RP2CD of 500 mg/m2 NUC-1031 on days 1 & 8 with AUC5 carboplatin day 1, every 3 weeks for 6 cycles. The ability to deliver carboplatin at AUC5 and the efficacy of this schedule even in patients with platinum-resistant disease makes this an attractive therapeutic combination. | |
dc.format.extent | 2340030 | |
dc.language.iso | eng | |
dc.relation.ispartof | Clinical Cancer Research | en |
dc.subject | Acelarin | en |
dc.subject | NUC-1031 | en |
dc.subject | Platinum-resistance | en |
dc.subject | Recurrent ovarian cancer | en |
dc.subject | RC0254 Neoplasms. Tumors. Oncology (including Cancer) | en |
dc.subject | RG Gynecology and obstetrics | en |
dc.subject | RM Therapeutics. Pharmacology | en |
dc.subject | E-NDAS | en |
dc.subject | SDG 3 - Good Health and Well-being | en |
dc.subject.lcc | RC0254 | en |
dc.subject.lcc | RG | en |
dc.subject.lcc | RM | en |
dc.title | A Phase IB open-label, dose-escalation study of NUC 1031 in combination with carboplatin for recurrent ovarian cancer | en |
dc.type | Journal article | en |
dc.contributor.institution | University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis | en |
dc.contributor.institution | University of St Andrews. Cellular Medicine Division | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.identifier.doi | 10.1158/1078-0432.CCR-20-4403 | |
dc.description.status | Peer reviewed | en |
dc.date.embargoedUntil | 2022-03-19 |
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