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544P - Phase I study of the irreversible FGFR inhibitor (i) futibatinib (FBN; TAS-120) in Japanese patients (pts) with advanced (adv) solid tumours

Presentation Number
544P
Speakers
  • Chigusa Morizane (Chuo-ku, Japan)
Date
17.09.2020

Abstract

Background

The FGFRi FBN showed tolerability and preliminary efficacy in a phase I dose-escalation (DE)/expansion (EX) study conducted in primarily Caucasian pts with adv solid tumours (NCT02052778), and 20 mg once-daily (QD) FBN was established as the recommended phase II dose (RP2D). Here, we report results from a Japanese phase I DE/EX study of FBN in adv solid tumours.

Methods

In DE, pts received 8–160 mg FBN thrice weekly (TIW; accelerated titration or standard 3+3 design), or 16 and 20 mg QD. The primary objective was safety and maximum tolerated dose (MTD) evaluation; secondary were pharmacokinetics (PK) and preliminary efficacy. The EX phase included pts with FGF/FGFR abnormalities receiving FBN at doses < MTD.

Results

Sixty-three pts were enrolled in 8 TIW (DE; 29 pts, EX; 11 pts) and 2 QD cohorts (DE; 10 pts, EX; 13 pts). Pts had colorectal (16%), esophageal (13%), gastric (13%), or biliary tract cancer (11%), and 52% had tumors with FGF/FGFR aberrations. No DLTs were observed in the study; MTD was not reached with TIW dosing. QD enrollment was based on prior phase I data and 20 mg QD was determined as the RP2D. Overall, 5% of pts experienced grade (gr) ≥3 treatment-related adverse events (TRAEs). Most common TRAEs (all gr; gr ≥3) were hyperphosphatemia (89%; 0), decreased appetite (22%; 0), nausea (19%; 0), stomatitis (14%; 2%), retinal detachment (13%; 0), and elevated AST (11%; 3%). TRAEs led to dose reductions, interruptions, and discontinuation in 24%, 48%, and 0% of pts, respectively. The PK profile of 20 mg QD FBN (mean Cmax, 253 ng/mL; AUC0-last, 977ng·h/mL; median Tmax, 2.00 h; apparent T1/2, 2.18 h) was similar to that observed in Caucasian pts. Efficacy assessment is ongoing; at data cutoff (July 4, 2019), partial responses were observed in pts with gastric (n=2; tumor shrinkages of 59% and 70%) and breast cancer (n=1; tumor shrinkage, 37%) harboring FGFR2 amplifications.

Conclusions

FBN showed manageable safety and preliminary efficacy in Japanese pts with adv solid tumors; RP2D (20 mg QD) in this study was consistent with prior results. Phase 2/3 studies in cholangiocarcinoma (NCT02052778; NCT04093362), gastric (NCT04189445) and breast tumours (NCT04024436) are ongoing.

Clinical trial identification

JapicCTI-142552.

Legal entity responsible for the study

Taiho Pharmaceutical Co., Ltd.

Funding

Taiho Pharmaceutical Co., Ltd.

Disclosure

C. Morizane: Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self): Novartis; Honoraria (self), Research grant/Funding (institution): Yakult Honsha; Honoraria (self): Teijin Pharma; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy: MSD K.K.; Research grant/Funding (institution): ONO Pharmaceutical; Research grant/Funding (institution): J-Pharma; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck biopharma; Advisory/Consultancy: AbbVie. T. Kojima: Advisory/Consultancy, Research grant/Funding (institution): Ono; Advisory/Consultancy, Research grant/Funding (institution): MSD; Research grant/Funding (institution): Shionogi; Research grant/Funding (institution): Astellas Amgen; Advisory/Consultancy: Astellas; Research grant/Funding (institution): Chugai; Advisory/Consultancy: Oncolys; Research grant/Funding (institution): Parexel; Research grant/Funding (institution): Merck Serono; Advisory/Consultancy: Merck Biopharma; Advisory/Consultancy: Bristol-Myers Squibb. Y. Kuboki: Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): ONO; Honoraria (self): Bayer; Honoraria (self): Sanofi; Honoraria (self): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Takeda; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Chugai; Research grant/Funding (institution): GSK. H. Bando: Honoraria (self): Taiho Parmaceutical; Honoraria (self): Eli Lilly Japan. N. Matsubara: Honoraria (self), Research grant/Funding (institution): Chugai Pharmaceutical Co.Ltd.; Honoraria (self), Research grant/Funding (institution): MSD K.K.,; Honoraria (self), Research grant/Funding (institution): Bayer Yakuhin, Ltd.,; Honoraria (self): Sanofi K.K.; Honoraria (self), Research grant/Funding (institution): Janssen Pharmaceutical K.K.; Research grant/Funding (institution): Astellas Pharma Inc.,; Research grant/Funding (institution): AstraZeneca K.K.; Research grant/Funding (institution): TAIHO Phamaceutical Co.,Ltd.; Research grant/Funding (institution): Pfizer Japan Inc.. K. Shitara: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: AbbVie ; Honoraria (self): Yakult; Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Takeda; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical; Advisory/Consultancy, Research grant/Funding (institution): Taiho Pharmaceutical; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: GlaxoSmithKline; Research grant/Funding (institution): Chugai Pharm; Research grant/Funding (institution): Medi Science; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Dainippon Sumitomo Pharma. K. Yoh: Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Lilly; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): Daiichi Sankyo; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Kyowa Kirin; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Takeda. H. Hirai: Full/Part-time employment: Taiho. T. Kato: Honoraria (self), Research grant/Funding institution): Taiho. T. Doi: Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self): Astellas; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Honoraria (self): Ono; Honoraria (self): Oncolys Biopharma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Taiho; Advisory/Consultancy: Amgen; Advisory/Consultancy, Research grant/Funding (institution): Sumitomo Dainippon; Advisory/Consultancy: Rakuten Medical; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy: Takeda; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Kyowa Hakko Kirin; Research grant/Funding (institution): IQVIA; Research grant/Funding (institution): Pfizer.

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Poster Display session

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)

Presentation Number
1165P
Speakers
  • Zhiwei Zhou (Guangzhou, China)
Date
17.09.2020

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, P=0.0012), Ki-67 >10% (8.3 vs 2.1 mo, HR 0.14, P<0.0001), foregut (8.4 vs 4.6 mo, HR 0.29, P=0.0001) and hindgut (8.3 vs 2.1 mo, HR 0.35, P=0.0014). There was numerical PFS improvement with surufatinib compared to placebo in the rest subgroups: Ki 67 <3% (13.9 vs 7.4 mo, HR 0.43, P=0.0557), midgut (19.2 vs 8.9 mo, HR not analyzed due to small sample size) and unknown origin (9.2 vs 5.5 mo, HR 0.56, P=0.2943). ORR in the subgroups of Ki-67 <3%, 3-10%, >10% with surufatinib were 4.8%, 7.7%% and 20.0% respectively. There was no objective response in the placebo arm. ORR in the subgroups of foregut, midgut and unknown origin with surufatinib was 18.4%, 16.7% and 10.0% respectively while no response was observed in subgroups of hindgut or other origins.

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.

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