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PRS-343 in Combination With Atezolizumab in HER2-Positive Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03650348
Recruitment Status : Active, not recruiting
First Posted : August 28, 2018
Last Update Posted : February 2, 2021
Information provided by (Responsible Party):
Pieris Pharmaceuticals, Inc.

Brief Summary:
A Phase 1b, open-label, dose escalation study of PRS-343 in combination with atezolizumab in patients with HER2-positive advanced or metastatic solid tumors.

Condition or disease Intervention/treatment Phase
HER2-positive Breast Cancer HER2-positive Gastric Cancer HER2-positive Bladder Cancer HER2-positive Solid Tumor Drug: PRS-343 in Combination with Atezolizumab Phase 1

Detailed Description:

This is a multicenter, open-label Phase 1b study to determine the MTD and RP2D and to assess the safety and efficacy of PRS-343 administered in combination with atezolizumab, a PD-L1 antibody, in previously treated advanced or metastatic HER-2 positive solid tumors (e.g., bladder, breast and gastrointestinal). The study will include a dose escalation period followed by an expansion period. PRS-343 and atezolizumab will be given intravenously once every three weeks (Q3W).

All available safety data, emerging PK, pharmacodynamic data, and dose limiting toxicities (DLTs) will be considered in guiding the Safety Committee's decisions regarding subsequent doses to be tested during the escalation phase of the study. Once the MTD and RP2D have been established, an expansion cohort will be enrolled.

One treatment cycle is defined as 21 days (3 weeks).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single Group Assignment Drug PRS-343 Combination Therapy
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b, Open-Label, Dose Escalation Study of PRS-343 in Combination With Atezolizumab in Patients With HER2-Positive Advanced or Metastatic Solid Tumors
Actual Study Start Date : August 21, 2018
Estimated Primary Completion Date : May 1, 2021
Estimated Study Completion Date : July 1, 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: PRS-343 in Combination with Atezolizumab Drug: PRS-343 in Combination with Atezolizumab
HER2/4-1BB Bispecific

Primary Outcome Measures :
  1. Incidence of DLTs and recommended Phase 2 dose (RP2D) of PRS-343 administered in combination with atezolizumab [ Time Frame: Up to 36 months ]

Secondary Outcome Measures :
  1. Overall response rate (ORR) per RECIST v1.1 [ Time Frame: Up to 36 months ]
  2. Duration of response (DOR) per RECIST v1.1 [ Time Frame: Up to 36 months ]
  3. Rate of complete response (CR) per RECIST v1.1 [ Time Frame: Up to 36 months ]
  4. Incidence and severity of AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03, and changes in clinical laboratory parameters [ Time Frame: Up to 36 months ]
  5. Peak Plasma Concentration (Cmax) [ Time Frame: Up to 36 months ]
  6. Area under the plasma concentration versus time curve (AUC) [ Time Frame: Up to 36 months ]
  7. Time to maximum dose concentration (Tmax) [ Time Frame: Up to 36 months ]
  8. Terminal half life (t1/2) [ Time Frame: Up to 36 months ]
  9. Presence and/or concentration of anti-PRS-343 and anti-atezolizumab antibodies (anti-drug antibodies [ADAs]) [ Time Frame: Up to 36 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Signed written informed consent obtained prior to performing any study procedure, including screening procedures.
  2. Men and women ≥18 years.
  3. Histologically or cytologically confirmed diagnosis of previously treated locally advanced and/or metastatic HER2+ solid tumor malignancy considered likely to respond to a HER2-targeted CD137 agonist (e.g. gastric/gastroesophageal/esophageal, breast, bladder).
  4. HER2+ status documented by clinical pathology report.
  5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
  6. Estimated life expectancy of at least 3 months.
  7. Measurable disease according to RECIST v1.1.
  8. Adequate organ function as defined below:
  9. Serum AST and ALT ≤ 2.5 X ULN or ≤ 5 X ULN in the presence of liver metastases.
  10. Total serum bilirubin ≤ 1.5 X ULN.
  11. Serum creatinine ≤ 2 X ULN OR calculated glomerular filtration rate (GFR) by Cockcroft-Gault formula ≥ 30 mL/min.
  12. Hemoglobin ≥ 9 g/dL.
  13. ANC ≥ 1500/mm3.
  14. Platelet count ≥ 75,000/mm3.
  15. Left ventricular ejection fraction (LVEF) determined by echocardiogram or multi-gated acquisition scan ≥ 50%.
  16. Any prior cumulative doxorubicin dose must be ≤ 360 mg/m2; prior cumulative epirubicin dose must be ≤ 720 mg/m2.
  17. Women of childbearing potential must have a negative serum or urine pregnancy test within 96 hours prior to start of study treatment.
  18. Women must not be breastfeeding.
  19. Women of childbearing potential must agree to follow instruction for method(s) of contraception for the duration of treatment with study drug PRS 343 and atezolizumab plus 5 months post-treatment completion.
  20. 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 treatment 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 virus (HBV) or hepatitis C virus (HCV) (unless patients are HBV DNA / HCV RNA negative).
  8. Any severe infection within 28 days prior to Cycle 1 Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia or active tuberculosis.
  9. Administration of live, attenuated vaccines within 28 days before Cycle 1 Day 1 or anticipated need of vaccination with live attenuated vaccine during the study.
  10. Need for the treatment of bacterial infection with oral or intravenous (IV) antibiotics within 14 days prior to Cycle 1 Day 1.
  11. History of infusion reactions to any component/excipient of PRS-343.
  12. History of infusion reactions to any component/excipient of atezolizumab.
  13. History of severe hypersensitivity reactions to monoclonal antibodies (mAbs).
  14. 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).
  15. 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.
  16. Prior organ transplantation including allogeneic or autologous stem-cell transplantation.
  17. 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) nausea and diarrhea if anti-emetic and anti-diarrheal treatment hasn't been exhausted.
  18. Concurrent or previous other malignancy within 5 years of study entry with the exception of cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy.
  19. Receipt of investigational treatment within 3 weeks of scheduled Cycle 1 Day 1 (C1D1) dosing.
  20. Receipt of cytotoxic chemotherapy within 3 weeks (6 weeks for nitrosoureas and mitomycin C) of scheduled C1D1 dosing.
  21. Receipt of radiation therapy within 3 weeks of scheduled Day 1 dosing, unless the radiation comprised a limited field to non-visceral structures (e.g., limb bone metastasis).
  22. Receipt of treatment with immunotherapy, biological therapies, hormonal therapies within 3 weeks of scheduled C1D1 dosing.
  23. Treatment with targeted small molecules within 5 half-lives of scheduled C1D1 dosing.
  24. 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.
  25. Receipt of atezolizumab or any other experimental drug that engages the same epitope as atezolizumab within 4 weeks of scheduled C1D1 dosing.
  26. Concurrent enrollment in another therapeutic clinical trial.
  27. Major surgery within 3 weeks of scheduled C1D1 dosing.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03650348

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United States, California
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States, 92663
UCLA Health
Santa Monica, California, United States, 90404
United States, Louisiana
Ochsner Cancer Institute
New Orleans, Louisiana, United States, 70121
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43202
United States, Texas
M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
NEXT Oncology
San Antonio, Texas, United States, 78240
Sponsors and Collaborators
Pieris Pharmaceuticals, Inc.
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Responsible Party: Pieris Pharmaceuticals, Inc. Identifier: NCT03650348    
Other Study ID Numbers: PRS-343-PCS_08_18
First Posted: August 28, 2018    Key Record Dates
Last Update Posted: February 2, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pieris Pharmaceuticals, Inc.:
HER2-positive breast cancer
HER2-positive gastric cancer
HER2-positive bladder cancer
Additional relevant MeSH terms:
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Stomach Neoplasms
Urinary Bladder Neoplasms
Neoplasms by Site
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Urologic Neoplasms
Urogenital Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Antineoplastic Agents