Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Discussion – NSCLC, metastatic

1857 - A Phase 1a/2a Trial of Sym015 - a MET Antibody Mixture - in Patients with Advanced Solid Tumors

Date

29 Sep 2019

Session

Poster Discussion – NSCLC, metastatic

Presenters

D. Ross Camidge

Citation

Annals of Oncology (2019) 30 (suppl_5): v602-v660. 10.1093/annonc/mdz260

Authors

D..R. Camidge1, F. Janku2, A. Martinez Bueno3, D.V. Catenacci4, J. Lee5, S. Lee6, H.C. Chung7, A. Dowlati8, K.S. Rohrberg9, E. Felip Font10, E. Garralda10, Y. Kang11, Y.W. Moon12, M. López Criado13, C. Chiu14, T.T. Poulsen15, H. Rudbæk15, L. Alifrangis15, R.P. Dalal15, A. Patnaik16

Author affiliations

  • 1 Medical Oncology Department, University of Colorado, 80045 - Aurora/US
  • 2 Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 3 . Insituto Oncológico Dr. Rosell., Hospital Quirón Dexeus, 08028 - Barcelona/ES
  • 4 Gastrointestinal Oncology Program, University of Chicago, Chicago/US
  • 5 Samsung Medical Center, Samsung Medical Center, Seoul/KR
  • 6 Department Of Medicine, Samsung Medical Center, Seoul/KR
  • 7 Department Of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 03722 - Seoul/KR
  • 8 Uh Cleveland Medical Center, UH Cleveland Medical Center, Cleveland/US
  • 9 Phase 1 Unit, Department Of Oncology, Rigshospitalet, University Hospital of Copenhagen, Denmark, 2100 - Copenhagen/DK
  • 10 Early Drug Development Unit, Vall d' Hebron Institute of Oncology (VHIO), 08035 - Barcelona/ES
  • 11 Oncology Dept, Asan Medical Center, University of Ulsan College of Medicine, 138-931 - Seoul/KR
  • 12 Hematology And Oncology, Cha Bundang Medical Center, Seongnam/KR
  • 13 Servicio De Oncología Médica, M.D. Anderson Cancer Center Madrid, Madrid/ES
  • 14 Division Of Hematology And Oncology, China Medical University Hospital, 404 - Taichung/TW
  • 15 Preclinical And Clinical Development, Symphogen A/S, 2750 - Ballerup/DK
  • 16 South Texas Oncology And Hematology, South Texas Oncology and Hematology, 78229 - San Antonio/US

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 1857

Background

MET gene amplification/mutation is implicated in oncogenesis of many tumor types. Sym015 is a recombinant antibody (Ab) mixture containing 2 humanized 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 (METEx14Δ) 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 METEx14Δ, 1 both) and gastric cancer (GC; 12 METAmp pts). Treatment-related 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 t½ of 7-10 days for the first dose. 83% METAmp concordance (10/12 samples) between tumor and blood was observed.Table:

1490PD

NSCLC PtMET Status (Local Assessment)Best Response (Best % Change From Baseline)Previous MET TKI therapyDuration of Response (weeks)
1METAmp NGS 6.8 CopiesPR (-53%)No80
2METAmp NGS >5 CopiesSD (-29%)No9, Ongoing
3METAmp NGS >5 CopiesSD (+3%)No9, Ongoing
4METEx14ΔSD (-28%)No7, Ongoing
5METAmp FISH MET/ CEP7:4.9SD (+6%)No11
6METEx14ΔSD (-4%)Yes8
7METEx14ΔSD (-21%)Yes15
8METEx14ΔSD (-20%)Yes8
9METAmp SISH MET/ CEP7: 15.2PendingNoOngoing
10METEx14ΔPendingYesOngoing
11METEx14Δ + METAmpPendingPendingOngoing
12METEx14ΔPendingNoOngoing
13METEx14ΔPendingNoOngoing
14METEx14ΔNot EvaluableYesNot 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 METEx14Δ. MET screening in blood seems feasible and may be included in future trials.

Clinical trial identification

NCT02648724.

Editorial acknowledgement

Legal entity responsible for the study

Symphogen A/S.

Funding

Symphogen A/S.

Disclosure

D.R. Camidge: Advisory / Consultancy: 2019: Takeda, CBT Pharmaceuticals, Daiichi-Sankyo (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): Symphogen. T.T. Poulsen: Full / Part-time employment: Symphogen A/S. H. Rudbæk: Full / Part-time 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.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.