PRS-343 in HER2-Positive Solid Tumors

NCT03330561 | Completed Phase 1 FDA Drug

• 1 other identifier: PRS-343-PCS_04_16
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 10

Brief Summary

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.

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; Bi-specific; 4-1BB; CD137; HER2

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03

  Up to 36 months

Secondary Outcomes (9)

• Peak Plasma Concentration (Cmax)

  Up to 36 months

• Area under the plasma concentration versus time curve (AUC)

  Up to 36 months

• Time to maximum dose concentration (Tmax)

  Up to 36 months

• Terminal half life (t1/2)

  Up to 36 months

• Tumor responses as defined by the Response Evaluation in Solid Tumors (RECIST) v.1.1

  Up to 36 months

Study Arms (1)

PRS-343

EXPERIMENTAL

Drug: PRS-343

Interventions

PRS-343 DRUG

PRS-343

Also known as: HER2/41BB Bispecific

PRS-343

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 pre-screening and screening procedures.
• Men and women ≥18 years.
• 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).
• Dose escalation and expansion cohort: HER2+ tumors documented by clinical pathology report:
• 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.
• Assessment of HER2 status in patients with gastric and gastroesophageal junction adenocarcinoma should follow the criteria published by Ruschoff et al. (38) as practicable.
• 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.
• 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.
• 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.
• Patients with breast cancer and gastric and gastroesophageal junction cancer must have received at least 1 prior HER2 targeted therapy for advanced/metastatic disease.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• Estimated life expectancy of at least 3 months.
• Measurable disease according to RECIST v1.1.
• Adequate organ function as defined below:

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 or hepatitis C infection. Patients with positive hepatitis B core antibody (HBcAb) require assessment and monitoring of virus deoxyribonucleic acid (DNA) status; patients with positive hepatitis C virus (HCV) core antibody can enroll if HCV ribonucleic acid (RNA) is negative. Patients with latent or active hepatitis B infection are excluded from the pre-treatment Cohort receiving obinutuzumab.
• History of infusion reactions to any component/excipient of PRS-343.
• 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). This criterion does not apply to patients receiving obinutuzumab as pre-treatment.
• 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.
• 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.
• Receipt of investigational treatment within 3 weeks of scheduled Cycle 1 Day 1 (C1D1) dosing.
• Receipt of cytotoxic chemotherapy within 3 weeks (6 weeks for nitrosoureas and mitomycin C) of scheduled C1D1 dosing.
• 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).
• Receipt of treatment with immunotherapy, biological therapies, targeted small molecules, hormonal therapies within 3 weeks of scheduled C1D1 dosing.

Sponsors & Collaborators

• Pieris Pharmaceuticals, Inc.: lead

Study Sites (10)

University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

University of California Los Angeles (UCLA)

Santa Monica, California, 90404, United States

Location

Georgetown University, Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, 15213, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

START - South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: None (Open Label)
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Drug PRS-343 Monotherapy

Study Record Dates

• First Submitted: October 19, 2017
• First Posted: November 6, 2017
• Study Start: September 13, 2017
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: April 22, 2024

Record last verified: 2024-04

Locations

US (10)