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Poster Display session 3

2391 - A phase 1 study of Sym021, an anti-PD-1 antibody (Ab), alone and in combination with Sym022 (anti-LAG-3) or Sym023 (anti-TIM-3)

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Immunotherapy

Tumour Site

Presenters

Anna Spreafico

Citation

Annals of Oncology (2019) 30 (suppl_5): v475-v532. 10.1093/annonc/mdz253

Authors

A. Spreafico1, F. Janku2, J.A. Rodon2, A.W. Tolcher3, S.R. Chandana4, M. Oliva1, S. Musalli5, L. Knauss5, M. Kragh5, L. Alifrangis5, C. Fröhlich5, M.C. Melander5, T. Blondal5, M.W. Pedersen5, J. Lantto5, D. Wood6, P.I. Nadler6, I.D. Horak5, L.L. Siu1, N. Lakhani4

Author affiliations

  • 1 Medical Oncology And Hematology, Princess Margaret Cancer Center, M5G 2M9 - Toronto/CA
  • 2 Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 3 Clinical Research, NEXT Oncology, San Antonio/US
  • 4 Developmental Therapeutics, START - Midwest, 40503 - Grand Rapids/US
  • 5 Preclinical And Clinical Development, Symphogen A/S, 2750 - Ballerup/DK
  • 6 Medical Research, Nadler Pharma Associates, 07869 - Randolph/US

Resources

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Abstract 2391

Background

Although anti-PD-(L)1 Abs are becoming standard of care for various cancers, combinations with other agents are being studied to improve the activity further. Sym021 is a high affinity, chicken-derived, humanized, effector-function silenced anti-PD-1 IgG1 Ab. Preclinical models demonstrate that Sym021 combined with Abs targeting other checkpoints (e.g., Sym022 an anti-lymphocyte activation gene 3 [LAG-3] Ab, Sym023 an anti-T-cell immunoglobulin mucin 3 [TIM-3] Ab) result in enhanced immunostimulatory and antitumor activity. We present here a first in human study of Sym021 alone and in combination with Sym022 or Sym023.

Methods

Safety, tolerability, and preliminary activity of Sym021 were evaluated on an every 2 week schedule at doses of 1, 3, and 10 mg/kg in patients (pts) with advanced solid tumor malignancies or lymphomas. Pre- and post-dosing blood samples were collected for assessment of PK profile, immunogenicity, and target engagement (ex vivo immune modulation). Based on these analyses, fixed dose Sym021 (3 mg/kg) was selected for further evaluation with increasing doses of Sym022 (0.3-10 mg/kg) or Sym023 (0.3-20 mg/kg) in combination arms of the trial.

Results

17 pts (median 61 years) received escalating doses of Sym021. Treatment-related adverse events (TRAEs; 21 total) occurred in 9 pts. Two pts discontinued treatment for grade (G) 3 autoimmune AEs considered dose-limiting toxicities (colitis at 10 mg/kg; arthritis at 3 mg/kg). Remaining TRAEs were G1-2; no G4 AEs or treatment-related deaths were observed. TRAEs in > 1 pt were fatigue and hypothyroidism (3 pts each). The PK profile was consistent with other monoclonal IgG1 Abs. Immune modulation as measured by ex vivo IL-2 release was observed in 11 of 13 evaluated pts. Two confirmed responses occurred (microsatellite stable gastric carcinoma [complete response at 10 mg/kg]; lacrimal gland ductal carcinoma [partial response at 3 mg/kg]).

Conclusions

Sym021 alone was well tolerated and demonstrated both immune modulation and antitumor activity. Evaluation of single agent dose-escalation trials of Sym022 and Sym023 and of the Sym021/Sym022 and Sym021/Sym023 combination arms are ongoing. Results from these studies will be presented.

Clinical trial identification

NCT03311412.

Editorial acknowledgement

Legal entity responsible for the study

Symphogen A/S.

Funding

Symphogen A/S.

Disclosure

A. Spreafico: Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Oncorus; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Surface Oncology; Research grant / Funding (institution): Northern Biologics; Research grant / Funding (institution): Janssen Oncology. F. Janku: Research grant / Funding (institution): Novartis, ; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): BioMed Valley Discoveries; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Agios; Research grant / Funding (institution): Plexxikon; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Piqur; Advisory / Consultancy, Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Asana; Research grant / Funding (institution): Upsher-Smith Laboratories; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: IFM Therapeutics; Advisory / Consultancy: Synlogic; Advisory / Consultancy: Deciphera; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Trovagene; Advisory / Consultancy: Immunomet. J.A. Rodon: Research grant / Funding (self): Bayer; Advisory / Consultancy, Research grant / Funding (self): Novartis ; Advisory / Consultancy, Research grant / Funding (institution): Spectrum Pharmaceuticals; Research grant / Funding (institution): Tocagen; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): BioAtla; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): GenMab; Research grant / Funding (institution): CytomX; Research grant / Funding (institution): Kelun-Biotech; Research grant / Funding (institution): Takeda-Millenium; Research grant / Funding (institution): Glaxosmithkline; Research grant / Funding (institution): Ipsen; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Orion Pharmaceuticals; Advisory / Consultancy: Servier Pharmaceuticals; Advisory / Consultancy: Peptomyc; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme; Advisory / Consultancy, Travel / Accommodation / Expenses: Kelun Pharmaceutical/Klus Pharma; Advisory / Consultancy: Roche Pharmaceuticals. A.W. Tolcher: Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy, Research grant / Funding (institution): Adagene; Advisory / Consultancy, Research grant / Funding (institution): ADC Therapeutics; Advisory / Consultancy: Agenus; Advisory / Consultancy: Aro Biotx; Advisory / Consultancy, Research grant / Funding (institution): Ascentage; Advisory / Consultancy: Aximmune; Advisory / Consultancy: Bayer; Advisory / Consultancy: Bioinvent; Advisory / Consultancy: Birdie; Advisory / Consultancy: Boston Medical (Syneos); Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Forbius; Advisory / Consultancy: Ignyta; Advisory / Consultancy: Immunome; Advisory / Consultancy: Immunomet; Advisory / Consultancy: Mekanistic; Advisory / Consultancy: Nanobiotix; Advisory / Consultancy, Research grant / Funding (institution): Symphogen; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Jazz Pharmaceuticals; Advisory / Consultancy: NBE Therapeutics; Advisory / Consultancy: Nuvalent; Advisory / Consultancy: Pelican; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Ridgeway; Advisory / Consultancy: Scitemex; Speaker Bureau / Expert testimony: Sesen (formerly Eleven BIO); Advisory / Consultancy: Syneos; Research grant / Funding (institution): Aminex; Research grant / Funding (institution): Asana; Research grant / Funding (institution): Arrys; Research grant / Funding (institution): Birdie; Research grant / Funding (institution): Cstone; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Inhibrx; Research grant / Funding (institution): Innate; Research grant / Funding (institution): Kiromic; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): Naturewise; Research grant / Funding (institution): Nextcure; Research grant / Funding (institution): Nitto Biopharma; Research grant / Funding (institution): Pieris; Research grant / Funding (institution): Syndax; Research grant / Funding (institution): Tizona; Research grant / Funding (institution): Zymeworks. S.R. Chandana: Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eisai; Advisory / Consultancy: Lilly; Research grant / Funding (institution): Novocure Ltd; Research grant / Funding (institution): ALX Oncology; Research grant / Funding (institution): Forty Seven Inc; Research grant / Funding (institution): INhibRx; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): Livzon; Research grant / Funding (institution): Forbius; Research grant / Funding (institution): Formation Biologics; Research grant / Funding (institution): Northern Biologics. M. Oliva: Honoraria (self): BMS; Honoraria (self): Merck; Research grant / Funding (institution): Symphogen. S. Musalli: Full / Part-time employment: Symphogen A/S. L. Knauss: Advisory / Consultancy, Full / Part-time employment: Symphogen A/S. M. Kragh: Shareholder / Stockholder / Stock options, Full / Part-time employment: Symphogen A/S. L. Alifrangis: Full / Part-time employment: Symphogen A/S. C. Fröhlich: Full / Part-time employment: Symphogen A/S. M.C. Melander: Full / Part-time employment: Symphogen A/S. T. Blondal: Full / Part-time employment: Symphogen. M.W. Pedersen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Symphogen A/S. J. Lantto: Shareholder / Stockholder / Stock options, Full / Part-time employment: Symphogen. D. Wood: Advisory / Consultancy: Symphogen; Advisory / Consultancy: Forbius; Advisory / Consultancy: Prism Pharma; Spouse / Financial dependant: Karyopharm. P.I. Nadler: Advisory / Consultancy, Leadership role: Forbius; Advisory / Consultancy: Symphogen A/S; Advisory / Consultancy: Karyopharm; Spouse / Financial dependant: Prism Pharma. I.D. Horak: Leadership role, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Symphogen A/S. L.L. Siu: Advisory / Consultancy, Research grant / Funding (institution): Merck ; Advisory / Consultancy, Research grant / Funding (institution): Pfizer ; Advisory / Consultancy, Research grant / Funding (institution): Celgene ; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca/MedImmune; Advisory / Consultancy: Morphosys ; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: GeneSeeq ; Advisory / Consultancy: Loxo; Advisory / Consultancy: Oncorus; Advisory / Consultancy, Research grant / Funding (institution): Symphogen; Advisory / Consultancy: Seattle Genetics; Research grant / Funding (self): Novartis; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Karyopharm; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Amgen. N. Lakhani: Research grant / Funding (institution): ALX Therapeutics; Research grant / Funding (institution): Amgen/Pfizer; Research grant / Funding (institution): Ascentage; Research grant / Funding (institution): Apexian; Research grant / Funding (institution): Asana Bioscience; Research grant / Funding (institution): Formation Biologics; Research grant / Funding (institution): Beigene Cerulean; Research grant / Funding (institution): Constellation; Research grant / Funding (institution): CytomX/Compugen; Research grant / Funding (institution): Forty Seven; Research grant / Funding (institution): Innovent Biologics; Research grant / Funding (institution): InhibRx/Incyte; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Jounce/Coordination; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): Livzon/TaiRx; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Northern Biologics; Research grant / Funding (institution): Regeneron.

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