PRS-343 in HER2-Positive Solid Tumors

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:
• •1. 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.
• •2. Assessment of HER2 status in patients with gastric and gastroesophageal junction adenocarcinoma should follow the criteria published by Ruschoff et al. (38) as practicable.
• •3. 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.
• •4. 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.
• •5. 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.
• •5. Patients with breast cancer and gastric and gastroesophageal junction cancer must have received at least 1 prior HER2 targeted therapy for advanced/metastatic disease.
• •6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• •7. Estimated life expectancy of at least 3 months.
• •8. Measurable disease according to RECIST v1.1.
• •9. Adequate organ function as defined below:
• •1. Serum AST and ALT ≤ 3 X ULN
• •2. Total serum bilirubin ≤ 1.5 X ULN
• •3. Serum creatinine ≤ 1.5 X ULN OR calculated glomerular filtration rate (GFR) by Cockcroft-Gault formula ≥ 50 mL/min
• •4. Hemoglobin ≥ 9 g/dL
• •5. ANC ≥ 1500/mm3
• •6. Platelet count ≥ 75,000/mm3
• •7. Left ventricular ejection fraction (LVEF) determined by echocardiogram or multi-gated acquisition scan ≥ 50%
• •10. Any prior cumulative doxorubicin dose must be ≤ 360 mg/m2; prior cumulative epirubicin dose must be ≤ 720 mg/m2.
• •11. Women of childbearing potential must have a negative serum or urine pregnancy test within 96 hours prior to start of study drug.
• •12. Women must not be breastfeeding.
• •13. 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.
• •14. 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.
• •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 or any other experimental drug that engages the same epitope as trastuzumab 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.