مؤتمر
Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced melanoma who are naive to anti-PD-1 therapy
| العنوان: | Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced melanoma who are naive to anti-PD-1 therapy |
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| المؤلفون: | Milhem, Mohammed M, Long, Georgina V, Hoimes, Christopher J, Amin, Asim, Lao, Christopher D, Conry, Robert Martin, Hunt, Jason, Daniels, Gregory A, Almubarak, Mohammed, Shaheen, Montaser F, Medina, Theresa Michelle, Barve, Minal A, Bishnoi, Sarwan K, Abdi, Ehtesham A |
| بيانات النشر: | American Society of Clinical Oncology (ASCO) |
| سنة النشر: | 2019 |
| المجموعة: | Griffith University: Griffith Research Online |
| مصطلحات موضوعية: | Clinical sciences, Oncology and carcinogenesis, Science & Technology, Life Sciences & Biomedicine |
| جغرافية الموضوع: | Chicago, IL |
| الوقت: | 2019-05-31 to 2019-06-04 |
| الوصف: | Background: SD-101 is a synthetic CpG TLR9 agonist. Pembrolizumab is a PD-1 inhibitor. SYNERGY-001/KEYNOTE-184 assesses the safety and preliminary efficacy of the combination of SD-101 and pembrolizumab in patients naïve to anti-PD-1/L1 therapy with unresectable stage IIIC-IV melanoma. Methods: SD-101 was evaluated as 2 mg/lesion injected into 1 to 4 lesions and 8 mg/lesion in 1 lesion as 4 weekly doses followed by 7 doses Q3W. Pembrolizumab was administered as 200 mg IV Q3W. CT scans were performed every 9 weeks. Responses were assessed per investigator using RECIST v1.1. Responses and post-hoc Kaplan-Meier analyses of PFS in the ITT population were compared for patients who received 2 mg/lesion with 8 mg/lesion. Results: 86 patients (2 mg: N = 45; 8 mg: N = 41) have been enrolled with similar baseline characteristics: median age = 66 years; male = 67%; ECOG stage 0 = 67%; disease stage: IIIC = 21%; IVM1a/b = 50%; IVM1c = 28%; LDH ≤ ULN = 71%; treatment naïve = 73%. Median follow up to date is 8.1 months in 2 mg group and 8.3 months in 8 mg group. SD-101 safety profile comprises flu-like symptoms with most frequent grade ≥3 SD-101-related AEs of headache (7%), fatigue (7%), malaise (5%), myalgia (4%), and chills (4%). Immune-related AEs were reported in 19%. ORR in 2 mg group = 71% (95% CI: 57, 82) (CR: 13%) and in 8 mg group = 49% (95% CI: 33, 65) (CR: 7%) with responses in both injected and non-injected lesions, including visceral. DOR = not reached (NR) in either group. ORR by baseline PD-L1 expression in 62 patients, 53% of whom were PD-L1 positive: 2 mg = 80%/79% (PD-L1 positive/negative); 8 mg = 62%/40% (PD-L1 positive/negative). PFS was higher in 2 mg group with median PFS in 2 mg = NR (95% CI: Not estimable [NE], NE) and in 8 mg = 10.4 months (95% CI: 4.2, NE), HR = 0.45 (95% CI: 0.21, 0.98), p = 0.036. 6 month PFS rate in 2 mg = 81% and in 8 mg = 60%. 6 month OS rate in 2 mg = 98% and in 8 mg = 92%. Conclusions: The TLR9 innate immune stimulant, SD-101, in combination with pembrolizumab has been ... |
| نوع الوثيقة: | conference object |
| اللغة: | English |
| تدمد: | 0732-183X |
| العلاقة: | Journal of Clinical Oncology; Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO); Milhem, MM; Long, GV; Hoimes, CJ; Amin, A; Lao, CD; Conry, RM; Hunt, J; Daniels, GA; Almubarak, M; Shaheen, MF; Medina, TM; Barve, MA; Bishnoi, SK; Abdi, EA; et al., Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced melanoma who are naive to anti-PD-1 therapy, Journal of Clinical Oncology, 2019, 37 (15); http://hdl.handle.net/10072/401564Test |
| DOI: | 10.1200/JCO.2019.37.15_suppl.9534 |
| الإتاحة: | https://doi.org/10.1200/JCO.2019.37.15_suppl.9534Test http://hdl.handle.net/10072/401564Test |
| حقوق: | open access |
| رقم الانضمام: | edsbas.F76F2B |
| قاعدة البيانات: | BASE |
| تدمد: | 0732183X |
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| DOI: | 10.1200/JCO.2019.37.15_suppl.9534 |