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Found 2 Presentations For Request "Abs%3A 347P"
347P - Results of the phase Ib dose escalation study of MEN1611, a PI3K inhibitor, combined with trastuzumab (T) ± fulvestrant (F) for HER2+/PIK3CA mutant (mut) advanced or metastatic (a/m) breast cancer (BC)
- Martine Piccart (Brussels, Belgium)
Abstract
Background
MEN1611 (MEN) is an oral PI3K inhibitor active on the p110α mut and WT, β and γ isoforms, while sparing the δ. Antitumor activity of MEN combined with other agents in patient-derived xenografts and BC cell lines with different
Methods
B-PRECISE-01 is an ongoing phase Ib study in patients (pts) with HER2+/
Results
As of Oct. 2019, 12 female pts were treated: 9 MEN+T+F and 3 MEN+T. Median age: 59 years (range 39-77). Median prior metastatic regimens: 5.5 (4-12). No DLTs were observed at any dose cohort. 48 mg was selected as RP2D. Most common grade (G)1/2 treatment-related adverse events (TRAEs) were diarrhoea (n=9), anemia (n=6), nausea (n=4), asthenia (n=4), decreased appetite (n=4), hyperglycemia (n=4), and mucosal inflammation (n=3). G3/4 TRAEs were not dose-dependent and occurred in 4 pts such as hyperglycemia (n=3), pneumonitis (n=1), decreased appetite (n=1), mucosal inflammation (n=1), and AST/ALT increase (n=1). Dose was reduced in one pt at 48 mg. No deaths from toxicity occurred. There were no overt differences in the safety profile of MEN+T+F vs. MEN+T. 5 pts (42%) had partial response, 5 stable disease, 4 disease control >8 months (mo) and 2 were on treatment >11 mo. MEN exposure tends to increase with increasing doses. Tmax was reached after 0.5-8 h following administration and the terminal half-life was ∼3.5 h.
Conclusions
Tolerability of MEN+T±F is acceptable; most TRAEs were reversible and manageable by supportive care. Promising antitumor activity in heavily pretreated pts, together with prolonged disease control, provide the rationale for cohort expansion at RP2D in pts with HER2+/
Clinical trial identification
NCT03767335.
Legal entity responsible for the study
Menarini Ricerche S.p.A.
Funding
Menarini Ricerche S.p.A.
Disclosure
M. Piccart: Speaker Bureau/Expert testimony, Board Member (Scientific Board): Oncolytics; Honoraria (self), Research grant/Funding (institution), Consultant: AstraZeneca; Honoraria (self), Consultant: Camel-IDS; Honoraria (self), Consultant: Crescendo Biologics; Honoraria (self), Consultant: Debiopharm; Honoraria (self), Consultant: G1 Therapeutics; Honoraria (self), Research grant/Funding (institution), Consultant: Genentech; Honoraria (self), Consultant: Huya; Honoraria (self), Consultant: Immunomedics; Honoraria (self), Research grant/Funding (institution), Consultant: Lilly; Honoraria (self), Consultant: Menarini; Honoraria (self), Research grant/Funding (institution), Consultant: MSD; Honoraria (self), Research grant/Funding (institution), Consultant: Novartis; Honoraria (self), Consultant: Odonate; Honoraria (self), Consultant: Periphagen; Honoraria (self), Research grant/Funding (institution), Consultant: Pfizer; Honoraria (self), Research grant/Funding (institution), Consultant: Roche; Honoraria (self), Consultant: Seattle Genetics; Research grant/Funding (institution): Radius; Research grant/Funding (institution): Servier; Research grant/Funding (institution): Synthon. F. Duhoux: Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Lilly; Travel/Accommodation/Expenses: Teva. H-T. Arkenau: Full/Part-time employment: HCAInternational; Full/Part-time employment: Sarah Cannon; Advisory/Consultancy: Lonctura; Advisory/Consultancy: Roche; Advisory/Consultancy: Bicycle; Advisory/Consultancy: Biontech; Advisory/Consultancy: Guardant; Advisory/Consultancy: Bayer; Advisory/Consultancy: Servier; Advisory/Consultancy: Taiho; Advisory/Consultancy: Boehringer Ingelheim. H. Wildiers: Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Biocartis; Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (institution), Advisory/Consultancy: PUMA Biotechnology; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (institution), Advisory/Consultancy: Sirtex. M. Campone: Honoraria (self), Advisory/Consultancy: GT1; Honoraria (institution), Advisory/Consultancy: Sanofi; Honoraria (institution), Advisory/Consultancy: Pierre Fabre; Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Servier; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (institution), Advisory/Consultancy: AbbVie; Honoraria (institution), Advisory/Consultancy: Accord; Honoraria (institution), Advisory/Consultancy: Pfizer; Speaker Bureau/Expert testimony: Lilly. D. Tosi: Travel/Accommodation/Expenses, Spouse/Financial dependant, An immediate family member: Biomarin; Spouse/Financial dependant, An immediate family member: Actelion; Research grant/Funding (self), Travel/Accommodation/Expenses: Astellas Pharma; Research grant/Funding (self): Jansen; Research grant/Funding (self): Ipsen; Licensing/Royalties, Pending patent on a new drug combination for prostate cancer treatment: Pending patent; Travel/Accommodation/Expenses, An immediate family member: Nutricia; Travel/Accommodation/Expenses, An immediate family member: Amicus Therapeutics; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: AstraZeneca. S. Escrivá-de Romaní: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pierre Fabre; Speaker Bureau/Expert testimony: Eisai; Research grant/Funding (institution): Synthon; Travel/Accommodation/Expenses: Daiichi Sankyo. A.M. Wardley: Honoraria (self), Honoraria (institution), Contract research: Roche; Honoraria (self), Honoraria (institution), Joint working agreement, contract research: Novartis; Honoraria (self), Joint working agreement, contract research: Pfizer; Honoraria (self), Honoraria (institution), Contract research: Daiichi Sankyo; Honoraria (institution), Contract research: Seattle Genetics; Honoraria (self), Honoraria (institution), Contract research: Eli Lilly; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses, Travel assistance: MSD; Honoraria (self): Athenex; Honoraria (self), Honoraria (institution), Contract research: AstraZeneca; Honoraria (self): Andrew Wardley Limited; Leadership role, Director: Manchester Cancer Academy; Leadership role, Director: Outreach Research & Innovation Group Limited; Honoraria (self): Gerson Lehman Group; Honoraria (self): Guidepoint Global; Honoraria (self): Coleman Expert Network; Honoraria (self): Helios; Honoraria (self): Health Care America; Honoraria (self): 1G1 Therapeutics, Inc.; Honoraria (self): Research Triangle Park, NC, USA. P.G. Aftimos: Honoraria (self): Boehringer Ingleheim; Honoraria (self): Macrogenics; Honoraria (self): Amcure; Honoraria (self): Synthon; Honoraria (self): G1 Therapeutics; Honoraria (self), Travel/Accommodation/Expenses, Travel grant: Roche; Honoraria (self): Novartis; Honoraria (self), Travel/Accommodation/Expenses, Travel grant: Amgen; Travel/Accommodation/Expenses, Travel grant: MSD; Travel/Accommodation/Expenses, Travel grant: Pfizer; Honoraria (self): Radius; Honoraria (self): Servier. F. Amair-Pinedo: Full/Part-time employment: Menarini Ricerche S.p.A./Laboratorios Menarini. A.U.E. Pellacani: Full/Part-time employment: Menarini Ricerche S.p.A.; Leadership role: VaxYnethic; Shareholder/Stockholder/Stock options: Amgen. D.O. Laurent: Leadership role, Full/Part-time employment: Menarini. All other authors have declared no conflicts of interest.
1165P - Subgroup analysis by Ki-67 and primary tumour origins of the randomized, placebo-controlled phase III study of surufatinib in advanced well-differentiated extrapancreatic neuroendocrine tumours (SANET-ep)
- Zhiwei Zhou (Guangzhou, China)
Abstract
Background
Surufatinib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (1,2,3), fibroblast growth factor receptor 1 and colony stimulating factor 1 receptor, has demonstrated superior efficacy in extrapancreatic neuroendocrine tumors (NETs) in a phase III study (SANET-ep, ESMO 2019 Abs. LBA76). The proliferation marker Ki-67 and primary tumor origins are the major prognostic factors in NETs.
Methods
The post-hoc efficacy analysis of surufatinib versus placebo was conducted by Ki-67 subcategory (<3%, 3-10%, >10%) and primary tumor origins (foregut, midgut, hindgut, others or unknown) in patients (pts) with advanced well-differentiated (grade 1 or 2) extrapancreatic NETs. The primary endpoint (progression-free survival [PFS]) and secondary endpoint (objective response rate [ORR]) both by investigator assessment (RECIST1.1) were analyzed.
Results
Median PFS was significantly prolonged with surufatinib compared to placebo in subgroups of Ki-67 3-10% (7.6 vs 4.6 months [mo], hazard ratio [HR] 0.47,
Conclusions
Surufatinib demonstrated clinically significant benefits for pts with advanced well-differentiated extrapancreatic NETs compared to placebo. Results of this exploratory analysis were consistent with those reported for the SANET-ep primary analysis, and improved outcomes were observed across major subgroups.
Clinical trial identification
NCT02588170.
Legal entity responsible for the study
Hutchison MediPharma Limited.
Funding
Hutchison MediPharma Limited.
Disclosure
J. Li, J. He: Full/Part-time employment: Hutchison MediPharma Limited. W. Su: Shareholder/Stockholder/Stock options, Full/Part-time employment: Hutchison MediPharma Limited. All other authors have declared no conflicts of interest.