The MEDIOLA phase I/II trial evaluated durvalumab and olaparib combination as a first- or second-line therapy. After a 4-week run-in with olaparib, patients were treated with olaparib at 300 mg orally twice daily, plus durvalumab at 1.5 g intravenously every 4 weeks, until disease progression or intolerable toxicity. In addition, the median DoR appeared longer with the combination (9.2 months in MEDIOLA vs 6.4 months in OlympiAD). Background. MEDIOLA: Phase II study of olaparib and durvalumab (MEDIOLA): Updated results in germline BRCA-mutated platinum sensitive relapsed (PSR) ovarian cancer (OC) Abstract #1190PD. Sunday 29 September, 10:30. Olaparib (Lynparza®) is a poly(ADP-ribose) polymerase (PARP) inhibitor approved as maintenance treatment of PSR OC. With a demonstrated disease control rate (DCR) of 80% in a phase II trial, the combination of olaparib (Lynparza) and durvalumab (Imfinzi) for pretreated patients with germline BRCA-mutated (gBRCAm), HER2-negative metastatic breast cancer shows great promise for future treatment.These findings, from the MEDIOLA trial, were presented at the 2017 San Antonio Breast Cancer Symposium. MEDIOLA is a phase I/II open-label, multicenter study evaluating the combination of olaparib and durvalumab in patients with advanced solid tumors who harborBRCAmutations. Study of Durvalumab+Olaparib or Durvalumab After Treatment With Durvalumab and Chemotherapy in Patients With Lung Cancer (ORION) (ORION) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. In addition, MEDIOLA is a phase I/II study of durvalumab in combination with olaparib in patients with advanced solid tumors, including SCLC. Conclusions: The addition of durvalumab to olaparib showed promising activity with the ORR in the early line gBRCAm MBC pts, comparing favorably with olaparib monotherapy (OlympiAD) (>70% in 1–2L MEDIOLA vs 60% overall in OlympiAD). MEDIOLA assessed olaparib in combination with the anti-programmed cell death ligand1 antibody, durvalumab, in germline BRCA1 and/or BRCA2 mutated (gBRCAm) PSR OC (NCT02734004). A single-arm, phase II trial (NCT02484404) enrolled patients with relapsed SCLC who received durvalumab, 1500 mg every 4 weeks, and olaparib, 300 mg twice a day.The primary outcome was objective response rate.
Similarly, all eight patients in cohort 2 who responded to olaparib had a somatic BRCA1/2 mutation and therefore the ORR for this subgroup (n=16) was 50% and the 18-week CBR was 67%.. Olaparib treatment did not elicit responses in the 10 patients with either germline or somatic ATM mutations, nor in the eight with germline CHEK2 mutations.. The most common immune-related AE were thyroid dysfunction of any grade, which was experienced in 47.0% of patients. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Valencia Auditorium (Hall 5) …
This study expanded the BRCA-mutant cohort to 100 patients. MEDIOLA. Methods. An open-label, phase II basket study of olaparib and durvalumab (MEDIOLA): Results in germline BRCA-mutated (gBRCAm) platinum-sensitive relapsed (PSR) … 42 In the Phase II MEDIOLA trial, durvalumab was combined with olaparib, another PARP inhibitor, in 25 patients with BRCA1/2-mutated, HER2– metastatic breast cancer with a confirmed ORR of 52% reported.
Mediola is an important clinical trial. This can lead to cancer developing. The MEDIOLA study is a phase II trial investigating the use of olaparib, which is a PARP inhibitor, in combination with durvalumab, a PD-L1 inhibitor, in BRCA1 and … A Phase II study (MEDIOLA) of olaparib and the PD-L1 inhibitor durvalumab in patients with relapsed, platinum-sensitive, BRCA-mutated ovarian cancer showed a good objective response rate (ORR) of 72% (n = 23/32) (NCT 02734004). Prof Susan Domchek speaks to ecancer at ESMO 2019 in Barcelona about a phase II study of olaparib and durvalumab in patients with germline …
AEs of the ongoing studies are still unknown, however, AEs of the majority of completed studies are shown in (Table (Table4 4). An open-label, multitumor, phase II basket study of olaparib and durvalumab (MEDIOLA): Results in germline BRCA -mutated (g BRCA m) HER2-negative metastatic breast cancer (MBC) [abstract].
Poster Discussion - Gynaecological cancers. Drew Y, de Jonge M, Hong S-H, et al. Background. By treating with a PARP inhibitor, such as olaparib, both DNA repair pathways will be shut off in the cancer cells, which makes the cancer cells more likely to respond to treatment. The phase I/II basket MEDIOLA trial (NCT02734004), evaluated the combination of olaparib and durvalumab in selected advanced solid cancers [48,49].
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In 32 patients with germline BRCA mutations, the combinatorial therapy had an ORR of 53% and a 12-weeks DCR of 47% with minimal adverse events ( 46 ). Olaparib (Lynparza ®) is a poly(ADP-ribose) polymerase (PARP) inhibitor that prevents the repair of single-strand DNA breaks.Durvalumab (Imfinzi ®) is a programmed cell death ligand 1 (anti-PD-L1) inhibitor, which functions by promoting antitumour immune responses.Inhibition of vascular endothelial growth factor (VEGF) has been reported to enhance PARP inhibitor activity.
In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX.