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Proffered Paper - Developmental therapeutics

525O - A phase I dose escalation study of PRS-343, a HER2/4-1BB bispecific molecule, in patients with HER2-positive malignancies


20 Sep 2020


Proffered Paper - Developmental therapeutics


Clinical Research

Tumour Site


Geoffrey Ku


Annals of Oncology (2020) 31 (suppl_4): S462-S504. 10.1016/annonc/annonc271


G. Ku1, J.C. Bendell2, A.W. Tolcher3, S.A. Hurvitz4, A. Krishnamurthy5, A.B. El-Khoueiry6, A. Patnaik7, R.T. Shroff8, A. Noonan9, N.M. Hahn10, M. Matrana11, M. Zettl12, K. Aviano13, L. Mar13, P. Jolicoeur13, S. Olwill12, I. Bruns14, S. Piha-Paul15

Author affiliations

  • 1 Medical Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 2 Medical Oncology, Sarah Cannon Research Institute, 37203 - Nashville/US
  • 3 Clinical Research Director, NEXT OncologyTM, 78229 - San Antonio/US
  • 4 Hematology/oncology Santa Monica, UCLA, 90404 - Santa Monica/US
  • 5 Division Of Hematology/ Oncology, University of Pittsburgh Hillman Cancer Center, 15232 - Pittsburgh/US
  • 6 Clinical Investigations Support Office, USC Norris Comprehensive Cancer Center, 90033 - Los Angeles/US
  • 7 Experimental Therapeutics, South Texas Accelerated Research Therapeutics, 78229 - San Antonio/US
  • 8 Medical Oncology, University of Arizona Cancer Center, Tucson/US
  • 9 Comprehensive Cancer Center, The Ohio State University, 43221 - Ohio/US
  • 10 Oncology And Urology, Greenberg Bladder Cancer Institute, Johns Hopkins University School of Medicine, 21287 - Baltimore/US
  • 11 Medical Oncology, Ochsner Medical Center, 70121 - New Orleans/US
  • 12 Translational Sciences, Pieris Pharmaceuticals, 85399 - Hallbergmoss/DE
  • 13 Clinical Development Department, PIERIS, 02109 - Boston/US
  • 14 Clinical Development Department, PIERIS, 10019 - New York/US
  • 15 Department Of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030 - Houston/US


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Abstract 525O


Anticalin® proteins are recombinant human proteins based on lipocalins. PRS-343, a first-in-class bispecific antibody-Anticalin fusion protein, targets HER2 and costimulatory immune receptor 4-1BB on T cells. Here, we report the results of a phase I trial in patients with HER2+ solid tumors.


PRS-343 was evaluated in sequential dose cohorts from 0.0005 to 18 mg/kg i.v. Doses were administered Q3W up to 8mg/kg, while doses at 8mg/kg were also given Q2W and Q1W and doses beyond 8mg/kg were administered Q2W. Primary study objectives included safety, tolerability and RP2D. Secondary objectives included ORR and DCR, PD response and PK profile. PD response (CD8+ T cell IHC) was assessed in tumor biopsies pre-/post-treatment.


70 patients enrolled (median age 61 years, 59% female, 83% Caucasian, median of four lines of prior therapy) with GC/GEJ (n=25); BC (n=16); gynecological cancer (n=6); CRC (n=10); BTC (n=5); UC (n=2); melanoma, pancreatic and salivary duct cancer (n=1 each) were treated with PRS-343. Based on PK analyses and kinetics of the CD8+ T cell expansion post-treatment, the minimal active dose was considered to be 2.5 mg/kg. 33 patients treated at active dose levels were evaluable for response with an ORR and DCR of 12% and 52% (3% CR, 9% PR, 40% SD), respectively. All objective responses were observed on the Q2W schedule, at/above doses of 8mg/kg; ORR was 40% and DCR was 70% (10% CR, 30% PR). At active doses, we observed pronounced post-treatment expansion of CD8+ T cells while there was no increase at doses below 2.5mg/kg. This effect was more pronounced in patients with a confirmed PR or prolonged SD. PRS-343 was well tolerated and the most frequent TRAEs were mild to moderate infusion related reaction (25%), nausea (7%), arthralgia (5%), vomiting (4%), chills (4%), and fatigue (4%). No DLT was noted. We will also present results of a PRS-343/atezolizumab combination trial in HER2+ solid tumors.


PRS-343 is the first 4-1BB bispecific to demonstrate encouraging evidence of safety and clinical benefit with a correlative PD effect. Based on these data, a phase II trial in gastric/GEJ cancer has been planned in combination with ramucirumab and paclitaxel.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study

Pieris Pharmaceuticals.


Pieris Pharmaceuticals.


M. Zettl: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pieris Pharmaceuticals. K. Aviano: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pieris Pharmaceuticals. L. Mar: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pieris Pharmaceuticals. P. Jolicoeur: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pieris Pharmaceuticals. S. Olwill: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Pieris Pharmaceuticals. I. Bruns: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Pieris Pharmaceuticals. All other authors have declared no conflicts of interest.

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