Efficacy and safety of IMO-2055, a novel TLR9 agonist, in combination with erlotinib (E) and bevacizumab (bev) in patients (pts) with advanced or metastatic non-small cell lung cancer (NSCLC) who have progressed following prior chemotherapy
| العنوان: | Efficacy and safety of IMO-2055, a novel TLR9 agonist, in combination with erlotinib (E) and bevacizumab (bev) in patients (pts) with advanced or metastatic non-small cell lung cancer (NSCLC) who have progressed following prior chemotherapy |
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| المؤلفون: | Thomas E. Boyd, Donald A. Richards, Guillaume de La Bourdonnaye, Paul Conkling, David Smith, Alain C. Mita, Maria Regina C. Flores, Alice S. Bexon, John Nemunaitis, David S. Wages |
| المصدر: | Journal of Clinical Oncology. 30:e18047-e18047 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Oncology, Agonist, Cancer Research, medicine.medical_specialty, Pathology, Chemotherapy, Immune Stimulation, Bevacizumab, business.industry, medicine.drug_class, medicine.medical_treatment, non-small cell lung cancer (NSCLC), TLR9, medicine.disease, Internal medicine, medicine, In patient, Erlotinib, business, medicine.drug |
| الوصف: | e18047 Background: IMO-2055 is a novel TLR-9 agonist with potential to enhance the efficacy of biologics and small molecules through immune stimulation. Xenograft data show anti-tumor synergy between IMO-2055, E and bev; E-bev has been evaluated in 2nd line NSCLC. Methods: Primary objective was to determine the recommended dose (RD) of IMO-2055 (dose range 0.08-0.48 mg/kg/w s.c.) with E 150mg/day p.o. and bev 15mg/kg q3w i.v. in a standard 3+3 design. An expansion cohort at the RD further determined safety and efficacy. Pts had AJCC stage 3/4 inoperable, histologically proven NSCLC where standard chemotherapy was not an option. Treatment was until progression (PD) or toxicity. Results: 36 pts were enrolled at 10 US sites from Nov ‘07 to Mar '11. 35 were treated/evaluable for safety; 33 for efficacy. Median age was 64, 58% were men, 81% white, 81% PS 1 with 69% adenocarcinomas and median 17 months since diagnosis. 44% pts were >2nd line. Pts received a median of 4.3 3-week cycles. 19 pts entered dose-escalation: 4 at 0.08 mg/kg, 6 at 0.16 mg/kg, 6 at 0.32 mg/kg, and 3 at 0.48 mg/kg IMO-2055. Two pts had DLTs: 1 grade 3 dehydration at 0.16 mg/kg, and 1 grade 3 fatigue at 0.48 mg/kg. RD was 0.32 mg/kg based on pharmacodynamic and clinical data: 17 more pts were treated at this dose. The most common AEs were diarrhea, nausea, fatigue and rash; most frequent grade 3-4 AEs were fatigue (9%), diarrhea (9%), anemia and dyspnea (both 6%), with no clear dose-relationship to IMO-2055. G3-4 hypertension was 0%, ATE 6% and hemorrhage 3%. Five pts died of PD on or within 30 days of study drug administration. Response rate was 12% with 79% disease control (SD+PR). Median PFS was 5.6 months (95% CI 3.9-7.2) and OS 16 months (95% CI 7.5-17.8) with 55% pts alive at 1 year. Conclusions: Addition of IMO-2055 to E-bev was well tolerated with no unexpected toxicity. The RD of IMO-2055 with E-bev is 0.32 mg/kg/w s.c. Median PFS and OS in this heavily pretreated population compare favorably with published E-bev data. IMO-2055 should be further explored in NSCLC. |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::07eff9ae96941a5092be460a4042cfc3Test https://doi.org/10.1200/jco.2012.30.15_suppl.e18047Test |
| رقم الانضمام: | edsair.doi...........07eff9ae96941a5092be460a4042cfc3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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