Clinical Trials /

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

NCT03650348

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PRS-343 in Combination With Atezolizumab in HER2-Positive Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: PRS-343-PCS_08_18
  • NCT ID: NCT03650348

Conditions

  • HER2-positive Breast Cancer
  • HER2-positive Gastric Cancer
  • HER2-positive Bladder Cancer
  • HER2-positive Solid Tumor

Interventions

DrugSynonymsArms
PRS-343 in Combination with AtezolizumabPRS-343 in Combination with Atezolizumab

Purpose

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.

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).
    

Trial Arms

NameTypeDescriptionInterventions
PRS-343 in Combination with AtezolizumabExperimental
  • PRS-343 in Combination with Atezolizumab

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of DLTs and recommended Phase 2 dose (RP2D) of PRS-343 administered in combination with atezolizumab
Time Frame:Up to 36 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall response rate (ORR) per RECIST v1.1
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Duration of response (DOR) per RECIST v1.1
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Rate of complete response (CR) per RECIST v1.1
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Peak Plasma Concentration (Cmax)
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Area under the plasma concentration versus time curve (AUC)
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Time to maximum dose concentration (Tmax)
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Terminal half life (t1/2)
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Presence and/or concentration of anti-PRS-343 and anti-atezolizumab antibodies (anti-drug antibodies [ADAs])
Time Frame:Up to 36 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pieris Pharmaceuticals, Inc.

Trial Keywords

  • HER2-positive breast cancer
  • HER2-positive gastric cancer
  • HER2-positive bladder cancer
  • Pieris
  • PRS-343
  • Anticalin
  • Bispecific
  • 4-1BB
  • CD137
  • HER2
  • Atezolizumab

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