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

NCT03650348 | Completed Phase 1 FDA Drug

• 1 other identifier: PRS-343-PCS_08_18
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 8

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Incidence of DLTs and recommended Phase 2 dose (RP2D) of PRS-343 administered in combination with atezolizumab

  Up to 36 months

Secondary Outcomes (9)

• Overall response rate (ORR) per RECIST v1.1

  Up to 36 months

• Duration of response (DOR) per RECIST v1.1

  Up to 36 months

• Rate of complete response (CR) per RECIST v1.1

  Up to 36 months

• 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

  Up to 36 months

• Peak Plasma Concentration (Cmax)

  Up to 36 months

Study Arms (1)

PRS-343 in Combination with Atezolizumab

EXPERIMENTAL

Drug: PRS-343 in Combination with Atezolizumab

Interventions

PRS-343 in Combination with Atezolizumab DRUG

HER2/4-1BB Bispecific

PRS-343 in Combination with Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent obtained prior to performing any study procedure, including screening procedures.
• Men and women ≥18 years.
• 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).
• HER2+ status documented by clinical pathology report.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
• Estimated life expectancy of at least 3 months.
• Measurable disease according to RECIST v1.1.
• Adequate organ function as defined below:
• Serum AST and ALT ≤ 2.5 X ULN or ≤ 5 X ULN in the presence of liver metastases.
• Total serum bilirubin ≤ 1.5 X ULN.
• Serum creatinine ≤ 2 X ULN OR calculated glomerular filtration rate (GFR) by Cockcroft-Gault formula ≥ 30 mL/min.
• Hemoglobin ≥ 9 g/dL.
• ANC ≥ 1500/mm3.
• Platelet count ≥ 75,000/mm3.
• Left ventricular ejection fraction (LVEF) determined by echocardiogram or multi-gated acquisition scan ≥ 50%.

You may not qualify if:

• 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.
• History of acute coronary syndromes, including myocardial infarction, coronary artery bypass graft, unstable angina, coronary angioplasty or stenting within past 24 weeks.
• 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).
• History of ejection fraction drop below the lower limit of normal with trastuzumab and/or pertuzumab.
• 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.
• 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.
• 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).
• 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.
• 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.
• Need for the treatment of bacterial infection with oral or intravenous (IV) antibiotics within 14 days prior to Cycle 1 Day 1.
• History of infusion reactions to any component/excipient of PRS-343.
• History of infusion reactions to any component/excipient of atezolizumab.
• History of severe hypersensitivity reactions to monoclonal antibodies (mAbs).
• 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).
• 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.

Sponsors & Collaborators

• Pieris Pharmaceuticals, Inc.: lead

Study Sites (8)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

UCLA Health

Santa Monica, California, 90404, United States

Location

Ochsner Cancer Institute

New Orleans, Louisiana, 70121, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43202, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78240, United States

Location

MeSH Terms

Interventions

atezolizumab

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Group Assignment Drug PRS-343 Combination Therapy

Study Record Dates

• First Submitted: August 27, 2018
• First Posted: August 28, 2018
• Study Start: August 21, 2018
• Primary Completion: August 11, 2022
• Study Completion: August 11, 2022
• Last Updated: April 22, 2024

Record last verified: 2024-04

Locations

US (8)