A Phase 1, Open-Label, Dose Escalation Study of PRS-343 in Patients With HER2-Positive Advanced or Metastatic Solid Tumors

Condition: HER2-positive Breast Cancer, HER2-positive Gastric Cancer, HER2-positive Bladder Cancer, HER2-positive Solid Tumor


  • Drug: PRS-343

Purpose: A multi center, open-label, Phase 1 dose escalation study with expansion cohort is designed to determine the MTD, RP2D and dosing schedule of PRS-343 in patients with HER2+ advanced or metastatic solid tumors.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03330561

Sponsor: Pieris Pharmaceuticals, Inc.

Primary Outcome Measures:

  • Measure: Incidence and severity of AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4
  • Time Frame: Up to 36 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Peak Plasma Concentration (Cmax)
  • Time Frame: Up to 36 months
  • Safety Issue:
  • Measure: Area under the plasma concentration versus time curve (AUC)
  • Time Frame: Up to 36 months
  • Safety Issue:
  • Measure: Time to maximum dose concentration (Tmax)
  • Time Frame: Up to 36 months
  • Safety Issue:
  • Measure: Terminal half life (t1/2)
  • Time Frame: Up to 36 months
  • Safety Issue:
  • Measure: Tumor responses as defined by the Response Evaluation in Solid Tumors (RECIST) v.1.1
  • Time Frame: Up to 36 months
  • Safety Issue:
  • Measure: Duration of response
  • Time Frame: Up to 36 months
  • Safety Issue:
  • Measure: Disease control rate
  • Time Frame: Up to 36 months
  • Safety Issue:

Estimated Enrollment: 78

Study Start Date: September 28, 2017

Phase: Phase 1


  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  1. Signed written informed consent obtained prior to performing any study procedure, including pre-screening and screening procedures.
  2. Men and women ≥18 years.
  3. Dose escalation: Histologically or cytologically confirmed diagnosis of unresectable/locally advanced and/or metastatic HER2+ solid tumor malignancy and for which standard therapies are not available, are no longer effective, are not tolerated, or have been declined by the patient. Expansion cohort: Locally advanced or metastatic HER2+ solid tumors considered likely to respond to a HER2-targeted CD137 agonist (e.g. gastric/gastroesophageal/esophageal, breast, bladder).
  4. Dose escalation and expansion cohort: HER2+ tumors documented by clinical pathology report:
  5. Assessment of HER2 status in patients with breast cancer should follow the 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria (37) as practicable.
  6. Assessment of HER2 status in patients with gastric and gastroesophageal junction adenocarcinoma should follow the criteria published by Ruschoff et al. (38) as practicable.
  7. Assessment of HER2 status in patients with non-breast/non-gastric cancers may follow local institutional criteria. These criteria should be made available to the Sponsor.
  8. All patients with breast and gastric/gastroesophageal junction cancers should have HER2 testing performed using a FDA approved test in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
  9. Patients for whom the clinical pathology report includes only IHC as 3+ (does not reflex to ISH) may enroll without written report of ISH determined HER2 copy number, provided the investigational site confirms that archival tissue is available.
  10. Patients with breast cancer and gastric and gastroesophageal junction cancer must have received at least 1 prior HER2 targeted therapy for advanced/metastatic disease.
  11. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-
  12. Estimated life expectancy of at least 3 months.
  13. Dose Escalation: Evaluable or measurable disease according to RECIST v1.1 Expansion Cohort (additional 30 patients) Measurable disease according to RECIST v1.
  14. Adequate organ function as defined below:
  15. Serum AST and ALT ≤ 3 X ULN
  16. Total serum bilirubin ≤ 1.5 X ULN
  17. Serum creatinine ≤ 1.5 X ULN OR calculated glomerular filtration rate (GFR) by Cockcroft-Gault formula ≥ 50 mL/min
  18. Hemoglobin ≥ 9 g/dL
  19. ANC ≥ 1500/mm3
  20. Platelet count ≥ 75,000/mm3
  21. Left ventricular ejection fraction (LVEF) determined by echocardiogram or multi-gated acquisition scan ≥ 50%
  22. Any prior cumulative doxorubicin dose must be ≤ 360 mg/m2; prior cumulative epirubicin dose must be ≤ 720 mg/m
  23. Women of childbearing potential must have a negative serum or urine pregnancy test within 96 hours prior to start of study drug.
  24. Women must not be breastfeeding.
  25. Women of childbearing potential must agree to follow instruction for method(s) of contraception for the duration of treatment with study drug PRS-343 plus 90 days post-treatment completion.
  26. Males who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug PRS 343 plus 90 days post-treatment completion.

Exclusion Criteria:

  1. Known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are clinically stable off steroids for at least 7 days prior to study treatment. Carcinomatous meningitis precludes a patient from study participation regardless of clinical stability.
  2. History of acute coronary syndromes, including myocardial infarction, coronary artery bypass graft, unstable angina, coronary angioplasty or stenting within past 24 weeks.
  3. History of or current Class II, III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system (Appendix B).
  4. History of ejection fraction drop below the lower limit of normal with trastuzumab and/or pertuzumab.
  5. Medical, psychiatric, cognitive or other conditions that compromise the patient’s ability to understand the patient information, to give informed consent, to comply with the study protocol or to complete the study.
  6. Any severe concurrent disease or condition (includes active infections, cardiac arrhythmia, interstitial lung disease) that in the judgment of the investigator would make study participation inappropriate for the patient.
  7. Previously known infection with human immunodeficiency virus (HIV); or hepatitis B or hepatitis C infection.
  8. History of infusion reactions to any component/excipient of PRS-3
  9. Systemic steroid therapy (>10 mg daily prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment (Note: topical, inhaled, nasal and ophthalmic steroids are not prohibited).
  10. Autoimmune disease that has required systemic treatment in the past (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
  11. Has not recovered from the adverse effect of previous anticancer treatments to pre-treatment baseline or Grade 1 except for alopecia, anemia (hemoglobin must meet the study inclusion criteria) and peripheral neuropathy (which must have recovered to ≤ Grade 2).
  12. History of a second primary cancer with the exception of 1) curatively treated non-melanomatous skin cancer, 2) curatively treated cervical or breast carcinoma in situ, or 3) other malignancy with no known active disease present and no treatment administered during the last 2 years.
  13. Receipt of investigational treatment within 3 weeks of scheduled Cycle 1 Day 1 (C1D1) dosing.
  14. Receipt of cytotoxic chemotherapy within 3 weeks (6 weeks for nitrosoureas and mitomycin C) of scheduled C1D1 dosing.
  15. Receipt of radiation therapy within 3 weeks of scheduled C1D1 dosing, unless the radiation comprised a limited field to non-visceral structures (e.g., limb bone metastasis).
  16. Receipt of treatment with immunotherapy, biological therapies, targeted small molecules, hormonal therapies within 3 weeks of scheduled C1D1 dosing.
  17. Receipt of trastuzumab or ado-trastuzumab emtansine within 4 weeks of scheduled C1D1 dosing.
  18. Concurrent enrollment in another therapeutic clinical trial.
  19. Major surgery within 3 weeks of scheduled C1D1 dosing.


  • Ingmar Bruns, MD PhD
  • +1-857-246-8998


  • University of Arizona Cancer Center
  • Tucson Arizona 85719 United States
  • University of California Los Angeles (UCLA)
  • Santa Monica California 90404 United States
  • Georgetown University, Lombardi Comprehensive Cancer Center
  • Washington District of Columbia 20007 United States
  • Johns Hopkins University School of Medicine
  • Baltimore Maryland 21287 United States
  • Memorial Sloan Kettering Cancer Center
  • New York New York 10065 United States
  • University of Pittsburgh Medical Center (UPMC)
  • Pittsburgh Pennsylvania 15213 United States
  • Sarah Cannon Research Institute
  • Nashville Tennessee 37203 United States
  • M.D. Anderson Cancer Center
  • Houston Texas 77030 United States
  • START – South Texas Accelerated Research Therapeutics, LLC
  • San Antonio Texas 78229 United States
  • NEXT Oncology
  • San Antonio Texas 78240 United States

View trial on ClinicalTrials.gov