HER2-positive Breast CancerPhase 1NCT03330561
PRS-343 in HER2-Positive Solid Tumors
A Phase 1 study testing PRS-343 in people with HER2-positive Breast Cancer and HER2-positive Gastric Cancer, run by Pieris Pharmaceuticals, Inc. at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-positive Breast Cancer, HER2-positive Gastric Cancer, HER2-positive Bladder Cancer
- What is being tested?
- PRS-343
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 10 sitesUnited States
- Study dates
- 13 Sep 2017to 1 Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 27Show fewer
- 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:
- Serum AST and ALT ≤ 3 X ULN
- Total serum bilirubin ≤ 1.5 X ULN
- Serum creatinine ≤ 1.5 X ULN OR calculated glomerular filtration rate (GFR) by Cockcroft-Gault formula ≥ 50 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%
- Any prior cumulative doxorubicin dose must be ≤ 360 mg/m2; prior cumulative epirubicin dose must be ≤ 720 mg/m2.
- Women of childbearing potential must have a negative serum or urine pregnancy test within 96 hours prior to start of study drug.
- Women must not be breastfeeding.
- 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.
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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.
- 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 has not been exhausted.
- 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.
- 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.
- Concurrent enrollment in another therapeutic clinical trial.
- Major surgery within 3 weeks of scheduled C1D1 dosing.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21287
M.D. Anderson Cancer Center
Houston, Texas, 77030
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Pittsburgh Medical Center (UPMC)
Pittsburgh, Pennsylvania, 15213
NEXT Oncology
San Antonio, Texas, 78229
START - South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, 78229
University of California Los Angeles (UCLA)
Santa Monica, California, 90404
University of Arizona Cancer Center
Tucson, Arizona, 85719
Georgetown University, Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007
About this study
Official title: A Phase 1, Open-Label, Dose Escalation Study of PRS-343 in Patients With HER2-Positive Advanced or Metastatic Solid Tumors
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.
Read the detailed description
The study will evaluate PRS-343 administered by intravenous (IV) infusion every 3 weeks (Schedule 1) initially. If safety, PK, and PD data suggest a different dosing schedule should be evaluated, Schedule 2 and/or 3 (dosing every 2 weeks in a 28-day cycle or once a week in a 21-day cycle, respectively) may be conducted. Separate MTDs may be determined for each schedule evaluated. Dose-limiting toxicities (DLTs) will be reported during the first cycle of each schedule (e.g., 21 days after the first dose in Cycle 1 for Schedule 1). Patients will be monitored for safety throughout the study. Dosing will continue until criteria for study drug discontinuation are met (disease progression or withdrawal from the study).
Patients with unknown HER2 status will be consented separately in a pre-screening visit in order to undergo HER2 testing prior to screening. All patients will be evaluated at screening (Day 28 to 1) and baseline (Day 1 predose).
Once the MTD has been established, up to 30 additional patients with locally advanced or metastatic HER2+ solid tumors considered likely to respond to a HER2 targeted CD137 agonist (e.g. gastric/gastroesophageal/esophageal, breast, bladder) may be enrolled in individual expansion cohorts. The expansion cohort will be enrolled at the MTD and/or at a lower dose level if safety/PD/PK/efficacy data support further evaluation of a lower dose level in order to determine the RP2D. The RP2D may be equivalent to or lower than the MTD.
An End-of-Treatment Visit will be performed at the time of treatment discontinuation. Patients will be evaluated 30 days after the End-of-Treatment Visit or prior to starting subsequent therapy, if sooner, at the Safety Follow-up Visit to assess any ongoing AEs as outlined in the protocol.
Obinutuzumab pre-treatment cohorts: The potential of obinutuzumab pre-treatment to reduce formation of ADA will be studied in a cohort of up to ten patients receiving PRS-343 at a dose of 8 mg/kg Q2 weeks (corresponding to Cohort 11b).
Patients will be assessed for tumor response/progression per RECIST v1.1
- Conditions
- HER2-positive Breast Cancer, HER2-positive Gastric Cancer, HER2-positive Bladder Cancer, HER2-positive Solid Tumor
- Being tested
- PRS-343
- Keywords
- HER2-positive breast cancer, HER2 -positive gastric cancer, HER2-positive bladder cancer, Pieris, PRS-343, Anticalin, Bi-specific, 4-1BB, CD137, HER2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PRS-343Drug
Also called HER2/41BB Bispecific
PRS-343
| Study group | Role | What they receive |
|---|---|---|
| PRS-343 | Experimental | Not described Receives: Drug: PRS-343 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03
Measured: Up to 36 months
Secondary outcomes (9)
Peak Plasma Concentration (Cmax)
Measured: Up to 36 months
Area under the plasma concentration versus time curve (AUC)
Measured: Up to 36 months
Time to maximum dose concentration (Tmax)
Measured: Up to 36 months
Terminal half life (t1/2)
Measured: Up to 36 months
Tumor responses as defined by the Response Evaluation in Solid Tumors (RECIST) v.1.1
Measured: Up to 36 months
Duration of response
Measured: Up to 36 months
Disease control rate
Measured: Up to 36 months
Presence of PRS-343 anti-drug antibodies
Measured: Up to 36 months
Biomarkers (CD137, soluable HER2, cell surface antigens for immunotyping) in tumor tissues and blood samples
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start13 Sep 2017
- Primary completion1 Dec 2023
- Study completion1 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-positive Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Drug PRS-343 Monotherapy
- Masking
- None (open label)
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pieris Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03330561
- Sponsor's protocol ID
- PRS-343-PCS_04_16
- Status last verified
- Apr 2024
- First submitted
- 19 Oct 2017
- Last updated
- 22 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Dose Escalation Study of PRS-343 in Patients With HER2-Positive Advanced or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT03330561
- Acronym / sponsor ID
- PRS-343-PCS_04_16
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Pieris Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Sep 2017 (actual)
- Primary completion
- 1 Dec 2023 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 6 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study will evaluate PRS-343 administered by intravenous (IV) infusion every 3 weeks (Schedule 1) initially. If safety, PK, and PD data suggest a different dosing schedule should be evaluated, Schedule 2 and/or 3 (dosing every 2 weeks in a 28-day cycle or once a week in a 21-day cycle, respectively) may be conducted. Separate MTDs may be determined for each schedule evaluated. Dose-limiting toxicities (DLTs) will be reported during the first cycle of each schedule (e.g., 21 days after the first dose in Cycle 1 for Schedule 1). Patients will be monitored for safety throughout the study. Dosing will continue until criteria for study drug discontinuation are met (disease progression or withdrawal from the study).
Patients with unknown HER2 status will be consented separately in a pre-screening visit in order to undergo HER2 testing prior to screening. All patients will be evaluated at screening (Day 28 to 1) and baseline (Day 1 predose).
Once the MTD has been established, up to 30 additional patients with locally advanced or metastatic HER2+ solid tumors considered likely to respond to a HER2 targeted CD137 agonist (e.g. gastric/gastroesophageal/esophageal, breast, bladder) may be enrolled in individual expansion cohorts. The expansion cohort will be enrolled at the MTD and/or at a lower dose level if safety/PD/PK/efficacy data support further evaluation of a lower dose level in order to determine the RP2D. The RP2D may be equivalent to or lower than the MTD.
An End-of-Treatment Visit will be performed at the time of treatment discontinuation. Patients will be evaluated 30 days after the End-of-Treatment Visit or prior to starting subsequent therapy, if sooner, at the Safety Follow-up Visit to assess any ongoing AEs as outlined in the protocol.
Obinutuzumab pre-treatment cohorts: The potential of obinutuzumab pre-treatment to reduce formation of ADA will be studied in a cohort of up to ten patients receiving PRS-343 at a dose of 8 mg/kg Q2 weeks (corresponding to Cohort 11b).
Patients will be assessed for tumor response/progression per RECIST v1.1
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Drug PRS-343 Monotherapy
| Arm | Type | Receives |
|---|---|---|
| PRS-343 | Experimental | Drug: PRS-343 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- 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:
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PRS-343Also: HER2/41BB BispecificPRS-343 | Drug | PRS-343 |
Primary outcome
Incidence and severity of AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03
Time frame: Up to 36 months
9 secondary outcomes
Peak Plasma Concentration (Cmax)
Time frame: Up to 36 months
Area under the plasma concentration versus time curve (AUC)
Time frame: Up to 36 months
Time to maximum dose concentration (Tmax)
Time frame: Up to 36 months
Terminal half life (t1/2)
Time frame: Up to 36 months
Tumor responses as defined by the Response Evaluation in Solid Tumors (RECIST) v.1.1
Time frame: Up to 36 months
Duration of response
Time frame: Up to 36 months
Disease control rate
Time frame: Up to 36 months
Presence of PRS-343 anti-drug antibodies
Time frame: Up to 36 months
Biomarkers (CD137, soluable HER2, cell surface antigens for immunotyping) in tumor tissues and blood samples
Time frame: Up to 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2024.
- Individual participant dataSharing planned: Undecided
Related trials for HER2-positive Breast Cancer
Not yet recruiting
Tolerability of Dalpiciclib vs. Abemaciclib/Ribociclib in Early HR+/HER2- Breast Cancer
Breast Cancer
Active, not recruitingPhase 3
Neoadjuvant Pyrotinib in HR-positive and HER2-low High-risk Early Breast Cancer
Breast Cancer Invasive, Hormone-receptor-positive Breast Cancer
Not yet recruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08165784 in People With PIK3CA-Mutated Advanced or Metastatic Solid Tumors
Advanced Breast Cancer, Advanced or Metastatic Breast Cancer
RecruitingPhase 2/3
A Study of BL-M07D1 With or Without Pertuzumab Versus Docetaxel + Carboplatin + Trastuzumab + Pertuzumab in Neoadjuvant Therapy for HER2-Positive Breast Cancer
HER2-positive Breast Cancer
Active, not recruiting
NearWave Optical Molecular Monitoring
Breast Cancer, HER2-positive Breast Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PRS-343 in people with HER2-positive Breast Cancer and HER2-positive Gastric Cancer, run by Pieris Pharmaceuticals, Inc. at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 (time frame: Up to 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2024.