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IIa trial of Sym015, a MET antibody mixture, in patients with advanced solid tumours
abstracts
Annals of Oncology
Table: 1490PD Best Response Previous Duration (Best % Change MET TKI of Response From Baseline) therapy (weeks)
NSCLC MET Status (Local Pt Assessment)
1 2 3 4 5 6 7 8 9 10 11 12 13 14
1490PD
A phase Ia/IIa trial of Sym015, a MET antibody mixture, in patients with advanced solid tumours
D.R. Camidge1, F. Janku2, A. Martinez Bueno3, D.V. Catenacci4, J. Lee5, S-H. Lee6, H.C. Chung7, A. Dowlati8, K.S. Rohrberg9, E. Felip Font10, E. Garralda10, Y-K. Kang11, opez Criado13, C-F. Chiu14, T.T. Poulsen15, H. Rudbæk15, Y.W. Moon12, M. L L. Alifrangis15, R.P. Dalal15, A. Patnaik16 1 Medical Oncology Department, University of Colorado, Aurora, CO, USA, 2 Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer ogico Dr. Rosell., Hospital Quir on Dexeus, Center, Houston, TX, USA, 3Insituto Oncol Barcelona, Spain, 4Gastrointestinal Oncology Program, University of Chicago, Chicago, IL, USA, 5Samsung Medical Center, Samsung Medical Center, Seoul, Republic of Korea, 6 Department of Medicine, Samsung Medical Center, Seoul, Republic of Korea, 7 Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea, 8UH Cleveland Medical Center, Cleveland, OH, USA, 9 Phase I Unit, Department of Oncology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark, 10Early Drug Development Unit, Vall d’ Hebron Institute of Oncology (VHIO), Barcelona, Spain, 11Oncology Deptartment, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Songpa-gu, Republic of Korea, 12 Hematology and Oncology, Cha Bundang Medical Center, Seongnam, Republic of Korea, 13Servicio de Oncologıa Me´dica, M.D. Anderson Cancer Center Madrid, Madrid, Spain, 14Division of Hematology and Oncology, China Medical University Hospital, Taichung, Taiwan, 15Preclinical and Clinical Development, Symphogen A/S, Ballerup, Denmark, 16South Texas Oncology and Hematology, South Texas Oncology and Hematology, San Antonio, TX, USA Background: MET gene amplification/mutation is implicated in oncogenesis of many tumor types. Sym015 is a recombinant antibody (Ab) mixture containing 2 humanized
v610 | NSCLC, Metastatic
METAmp NGS 6.8 Copies METAmp NGS >5 Copies METAmp NGS >5 Copies METEx14D METAmp FISH MET/ CEP7:4.9 METEx14D METEx14D METEx14D METAmp SISH MET/ CEP7: 15.2 METEx14D METEx14D þ METAmp METEx14D METEx14D METEx14D
PR (-53%) SD (-29%) SD (þ3%) SD (-28%) SD (þ6%)
No No No No No
80 9, Ongoing 9, Ongoing 7, Ongoing 11
SD (-4%) SD (-21%) SD (-20%) Pending
Yes Yes Yes No
8 15 8 Ongoing
Pending Pending Pending Pending Not Evaluable
Yes Pending No No Yes
Ongoing Ongoing Ongoing Ongoing Not Evaluable
Conclusions: Sym015 was well tolerated with early evidence of antitumor activity. Predictive biomarker analysis is underway. The study continues to enroll NSCLC patients with METAmp and/or METEx14D. MET screening in blood seems feasible and may be included in future trials. Clinical trial identification: NCT02648724. Legal entity responsible for the study: Symphogen A/S. Funding: Symphogen A/S. Disclosure: D.R. Camidge: Advisory / Consultancy: 2019: Takeda, CBT Pharmaceuticals, DaiichiSankyo (ILD adjudication committee), G1 Therapeutics (DSMB), Bio-Thera (DSMB), Blueprint; Advisory / Consultancy: 2018: AstraZeneca, Takeda, Arrys/Kyn, Regeneron, Hengrui, G1 Therapeutics (DSMB), Daiichi Sankyo (ILD adjudication committee), Hansoh (SRC), Bio-Thera (DSMB), Ribon, BMS, Blueprint, Roche/Genentech, Inivata; Advisory / Consultancy: 2017: Genoptix, G1 Therapeutics (DSMB), Mersana Therapeutics, Roche/Genentech, Takeda, Ignyta, Daiichi Sankyo (ILD adjudication committee), Hansoh SRC, Bio-Thera DSMB, Lycera, Revolution Med; Research grant / Funding (self), Research grant / Funding (institution): 2017: Takeda Investigator-initiated Trial; Research grant / Funding (self), Research grant / Funding (institution), Company Sponsored Trials at Institution: 2018/9: AbbVie, AstraZeneca, BMS, Hansoh, Lycera, MedImmune, Merck, Pfizer, Phosplatin, Roche/Genentech, Seattle Genetics, Symphogen, Takeda. F. Janku: Research grant / Funding (self): Novartis, Genentech, BioMed Valley Discoveries, Astellas, Agios, Plexxikon, Deciphera, Piqur, Symphogen, Bristol-Myers Squibb, Asana, Upsher-Smith Laboratories; Advisory / Consultancy: Guardant Health, IFM Therapeutics, Synlogic, Deciphera; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Trovagene; Advisory / Consultancy: Immunomet. D.V. Catenacci: Honoraria (self), Advisory / Consultancy: Merck, BMS, Lilly, Astellas, Gritstone, Taiho, Five Prime, Genentech Roche, Foundation Medicine, Guardant Health, Tempus. H.C. Chung: Honoraria (self): Merck-Serono, Lilly, Foundation Medicine; Advisory / Consultancy: Taiho, Celltrion, MSD, Lilly,Quintiles, BMS, Merck-Serono; Research grant / Funding (institution): Lilly, GSK, MSD, Merck-Serono, BMS-ONO, Taiho. A. Dowlati: Advisory / Consultancy: Seattle genetics, Takeda, AbbVie; Research grant / Funding (institution): Takeda, Taiho, Roche, EMD Serono, Bayer, Tesaro, Regeneron, Amgen, Mirati, BMS. K.S. Rohrberg: Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Loxo Oncology, Orion Pharma, Pfizer, PUMA, Cantargia, Genmab, Novartis, Incyte, Bayer, AstraZeneca, Alligator, Merck, BMS; Travel / Accommodation / Expenses: Sanofi; Research grant / Funding (institution):
Volume 30 | Supplement 5 | October 2019
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Abs binding non-overlapping epitopes on MET which has superior preclinical activity compared to other MET Abs. Here we present interim results from the First in Human study of Sym015. Methods: In part 1 dose escalation, Sym015 was evaluated on every 2-week (q2w) schedule at 6/12/18/24 mg/kg doses in late line advanced solid tumor patients (pts). Based on PK/PD assessment, 18 mg/kg loading dose followed by 12 mg/kg q2w was selected as RP2D. The on-going Part 2 Dose expansion enrolls pts with MET amplification (METAmp >5 MET copies by Next Generation Sequencing (NGS) or FISH MET/ CEP7 ratio >2.2 updated to 3.0) and/or MET exon 14 deletion (METEx14D) positive tumors. Central FISH confirmation of tumor MET status and longitudinal circulating tumor (ct)DNA profiling is performed. Results: By April 2019, 51 pts (median age 61 yrs) have been treated, 12 pts in Part 1 and 39 pts in Part 2, the majority are non small cell lung cancer (NSCLC; 14 pts; 6 METAmp,7 METEx14D, 1 both) and gastric cancer (GC; 12 METAmp pts). Treatmentrelated adverse events (TRAE) occurred overall in 41,2%; TRAE gr3 in 9,8% (edema, colitis, septic shock, hypoalbuminemia, hypophosphatemia, increased amylase). No pts discontinued or died due to TRAE. The most common TRAE of 5% were fatigue 15.7%, peripheral edema 7,8%, nausea, decreased appetite, pruritus and abdominal pain reported by 5.9% of pts each. The table shows preliminary efficacy in NSCLC patients. Sym015 PK was slightly non-linear, with a dose-dependent t1=2 of 7-10 days for the first dose. 83% METAmp concordance (10/12 samples) between tumor and blood was observed.
Annals of Oncology
abstracts
Symphogen. T.T. Poulsen: Full / Part-time employment: Symphogen A/S. H. Rudbæk: Full / Parttime employment: Symphogen A/S. L. Alifrangis: Full / Part-time employment: Symphogen A/S. R.P. Dalal: Full / Part-time employment: Symphogen A/S. All other authors have declared no conflicts of interest.
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Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz260 | v611
Annals of Oncology
Table: 1490PD Best Response Previous Duration (Best % Change MET TKI of Response From Baseline) therapy (weeks)
NSCLC MET Status (Local Pt Assessment)
1 2 3 4 5 6 7 8 9 10 11 12 13 14
1490PD
A phase Ia/IIa trial of Sym015, a MET antibody mixture, in patients with advanced solid tumours
D.R. Camidge1, F. Janku2, A. Martinez Bueno3, D.V. Catenacci4, J. Lee5, S-H. Lee6, H.C. Chung7, A. Dowlati8, K.S. Rohrberg9, E. Felip Font10, E. Garralda10, Y-K. Kang11, opez Criado13, C-F. Chiu14, T.T. Poulsen15, H. Rudbæk15, Y.W. Moon12, M. L L. Alifrangis15, R.P. Dalal15, A. Patnaik16 1 Medical Oncology Department, University of Colorado, Aurora, CO, USA, 2 Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer ogico Dr. Rosell., Hospital Quir on Dexeus, Center, Houston, TX, USA, 3Insituto Oncol Barcelona, Spain, 4Gastrointestinal Oncology Program, University of Chicago, Chicago, IL, USA, 5Samsung Medical Center, Samsung Medical Center, Seoul, Republic of Korea, 6 Department of Medicine, Samsung Medical Center, Seoul, Republic of Korea, 7 Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea, 8UH Cleveland Medical Center, Cleveland, OH, USA, 9 Phase I Unit, Department of Oncology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark, 10Early Drug Development Unit, Vall d’ Hebron Institute of Oncology (VHIO), Barcelona, Spain, 11Oncology Deptartment, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Songpa-gu, Republic of Korea, 12 Hematology and Oncology, Cha Bundang Medical Center, Seongnam, Republic of Korea, 13Servicio de Oncologıa Me´dica, M.D. Anderson Cancer Center Madrid, Madrid, Spain, 14Division of Hematology and Oncology, China Medical University Hospital, Taichung, Taiwan, 15Preclinical and Clinical Development, Symphogen A/S, Ballerup, Denmark, 16South Texas Oncology and Hematology, South Texas Oncology and Hematology, San Antonio, TX, USA Background: MET gene amplification/mutation is implicated in oncogenesis of many tumor types. Sym015 is a recombinant antibody (Ab) mixture containing 2 humanized
v610 | NSCLC, Metastatic
METAmp NGS 6.8 Copies METAmp NGS >5 Copies METAmp NGS >5 Copies METEx14D METAmp FISH MET/ CEP7:4.9 METEx14D METEx14D METEx14D METAmp SISH MET/ CEP7: 15.2 METEx14D METEx14D þ METAmp METEx14D METEx14D METEx14D
PR (-53%) SD (-29%) SD (þ3%) SD (-28%) SD (þ6%)
No No No No No
80 9, Ongoing 9, Ongoing 7, Ongoing 11
SD (-4%) SD (-21%) SD (-20%) Pending
Yes Yes Yes No
8 15 8 Ongoing
Pending Pending Pending Pending Not Evaluable
Yes Pending No No Yes
Ongoing Ongoing Ongoing Ongoing Not Evaluable
Conclusions: Sym015 was well tolerated with early evidence of antitumor activity. Predictive biomarker analysis is underway. The study continues to enroll NSCLC patients with METAmp and/or METEx14D. MET screening in blood seems feasible and may be included in future trials. Clinical trial identification: NCT02648724. Legal entity responsible for the study: Symphogen A/S. Funding: Symphogen A/S. Disclosure: D.R. Camidge: Advisory / Consultancy: 2019: Takeda, CBT Pharmaceuticals, DaiichiSankyo (ILD adjudication committee), G1 Therapeutics (DSMB), Bio-Thera (DSMB), Blueprint; Advisory / Consultancy: 2018: AstraZeneca, Takeda, Arrys/Kyn, Regeneron, Hengrui, G1 Therapeutics (DSMB), Daiichi Sankyo (ILD adjudication committee), Hansoh (SRC), Bio-Thera (DSMB), Ribon, BMS, Blueprint, Roche/Genentech, Inivata; Advisory / Consultancy: 2017: Genoptix, G1 Therapeutics (DSMB), Mersana Therapeutics, Roche/Genentech, Takeda, Ignyta, Daiichi Sankyo (ILD adjudication committee), Hansoh SRC, Bio-Thera DSMB, Lycera, Revolution Med; Research grant / Funding (self), Research grant / Funding (institution): 2017: Takeda Investigator-initiated Trial; Research grant / Funding (self), Research grant / Funding (institution), Company Sponsored Trials at Institution: 2018/9: AbbVie, AstraZeneca, BMS, Hansoh, Lycera, MedImmune, Merck, Pfizer, Phosplatin, Roche/Genentech, Seattle Genetics, Symphogen, Takeda. F. Janku: Research grant / Funding (self): Novartis, Genentech, BioMed Valley Discoveries, Astellas, Agios, Plexxikon, Deciphera, Piqur, Symphogen, Bristol-Myers Squibb, Asana, Upsher-Smith Laboratories; Advisory / Consultancy: Guardant Health, IFM Therapeutics, Synlogic, Deciphera; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Trovagene; Advisory / Consultancy: Immunomet. D.V. Catenacci: Honoraria (self), Advisory / Consultancy: Merck, BMS, Lilly, Astellas, Gritstone, Taiho, Five Prime, Genentech Roche, Foundation Medicine, Guardant Health, Tempus. H.C. Chung: Honoraria (self): Merck-Serono, Lilly, Foundation Medicine; Advisory / Consultancy: Taiho, Celltrion, MSD, Lilly,Quintiles, BMS, Merck-Serono; Research grant / Funding (institution): Lilly, GSK, MSD, Merck-Serono, BMS-ONO, Taiho. A. Dowlati: Advisory / Consultancy: Seattle genetics, Takeda, AbbVie; Research grant / Funding (institution): Takeda, Taiho, Roche, EMD Serono, Bayer, Tesaro, Regeneron, Amgen, Mirati, BMS. K.S. Rohrberg: Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Loxo Oncology, Orion Pharma, Pfizer, PUMA, Cantargia, Genmab, Novartis, Incyte, Bayer, AstraZeneca, Alligator, Merck, BMS; Travel / Accommodation / Expenses: Sanofi; Research grant / Funding (institution):
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz260.012/5577531 by guest on 25 October 2019
Abs binding non-overlapping epitopes on MET which has superior preclinical activity compared to other MET Abs. Here we present interim results from the First in Human study of Sym015. Methods: In part 1 dose escalation, Sym015 was evaluated on every 2-week (q2w) schedule at 6/12/18/24 mg/kg doses in late line advanced solid tumor patients (pts). Based on PK/PD assessment, 18 mg/kg loading dose followed by 12 mg/kg q2w was selected as RP2D. The on-going Part 2 Dose expansion enrolls pts with MET amplification (METAmp >5 MET copies by Next Generation Sequencing (NGS) or FISH MET/ CEP7 ratio >2.2 updated to 3.0) and/or MET exon 14 deletion (METEx14D) positive tumors. Central FISH confirmation of tumor MET status and longitudinal circulating tumor (ct)DNA profiling is performed. Results: By April 2019, 51 pts (median age 61 yrs) have been treated, 12 pts in Part 1 and 39 pts in Part 2, the majority are non small cell lung cancer (NSCLC; 14 pts; 6 METAmp,7 METEx14D, 1 both) and gastric cancer (GC; 12 METAmp pts). Treatmentrelated adverse events (TRAE) occurred overall in 41,2%; TRAE gr3 in 9,8% (edema, colitis, septic shock, hypoalbuminemia, hypophosphatemia, increased amylase). No pts discontinued or died due to TRAE. The most common TRAE of 5% were fatigue 15.7%, peripheral edema 7,8%, nausea, decreased appetite, pruritus and abdominal pain reported by 5.9% of pts each. The table shows preliminary efficacy in NSCLC patients. Sym015 PK was slightly non-linear, with a dose-dependent t1=2 of 7-10 days for the first dose. 83% METAmp concordance (10/12 samples) between tumor and blood was observed.
Annals of Oncology
abstracts
Symphogen. T.T. Poulsen: Full / Part-time employment: Symphogen A/S. H. Rudbæk: Full / Parttime employment: Symphogen A/S. L. Alifrangis: Full / Part-time employment: Symphogen A/S. R.P. Dalal: Full / Part-time employment: Symphogen A/S. All other authors have declared no conflicts of interest.
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz260.012/5577531 by guest on 25 October 2019
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz260 | v611