HER2-positive Breast CancerPhase 1NCT03650348
PRS-343 in Combination With Atezolizumab in HER2-Positive Solid Tumors
A Phase 1 study testing PRS-343 in Combination with Atezolizumab in people with HER2-positive Breast Cancer and HER2-positive Gastric Cancer, run by Pieris Pharmaceuticals, Inc. at 8 sites in United States.
Trial 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. 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 in Combination with Atezolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 8 sitesUnited States
- Study dates
- 21 Aug 2018to 11 Aug 2022
- 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 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.
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- 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%.
- 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 treatment.
- 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 and atezolizumab plus 5 months 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 treatment 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.
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- 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.
- Prior organ transplantation including allogeneic or autologous stem-cell transplantation.
- 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.
- 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.
- 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 Day 1 dosing, unless the radiation comprised a limited field to non-visceral structures (e.g., limb bone metastasis).
- Receipt of treatment with immunotherapy, biological therapies, hormonal therapies within 3 weeks of scheduled C1D1 dosing.
- Treatment with targeted small molecules within 5 half-lives 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.
- Receipt of atezolizumab or any other experimental drug that engages the same epitope as atezolizumab 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
8 sites in 1 country.
8 sites in 1 country
United States8 sites
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43202
M.D. Anderson Cancer Center
Houston, Texas, 77030
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Ochsner Cancer Institute
New Orleans, Louisiana, 70121
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663
NEXT Oncology
San Antonio, Texas, 78240
UCLA Health
Santa Monica, California, 90404
About this study
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
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.
Read the 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).
- Conditions
- HER2-positive Breast Cancer, HER2-positive Gastric Cancer, HER2-positive Bladder Cancer, HER2-positive Solid Tumor
- Being tested
- PRS-343 in Combination with Atezolizumab
- Keywords
- HER2-positive breast cancer, HER2-positive gastric cancer, HER2-positive bladder cancer, Pieris, PRS-343, Anticalin, Bispecific, 4-1BB, CD137, HER2, Atezolizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PRS-343 in Combination with AtezolizumabDrug
HER2/4-1BB Bispecific
| Study group | Role | What they receive |
|---|---|---|
| PRS-343 in Combination with Atezolizumab | Experimental | Not described Receives: Drug: PRS-343 in Combination with Atezolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of DLTs and recommended Phase 2 dose (RP2D) of PRS-343 administered in combination with atezolizumab
Measured: Up to 36 months
Secondary outcomes (9)
Overall response rate (ORR) per RECIST v1.1
Measured: Up to 36 months
Duration of response (DOR) per RECIST v1.1
Measured: Up to 36 months
Rate of complete response (CR) per RECIST v1.1
Measured: 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
Measured: Up to 36 months
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
Presence and/or concentration of anti-PRS-343 and anti-atezolizumab antibodies (anti-drug antibodies [ADAs])
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 posted28 Aug 2018
- Study start21 Aug 2018
- Primary completion11 Aug 2022
- Study completion11 Aug 2022
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
- Single Group Assignment Drug PRS-343 Combination Therapy
- Masking
- None (open label)
- Enrolment
- 41 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
- NCT03650348
- Sponsor's protocol ID
- PRS-343-PCS_08_18
- Status last verified
- Apr 2024
- First submitted
- 27 Aug 2018
- 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 1b, Open-Label, Dose Escalation Study of PRS-343 in Combination With Atezolizumab in Patients With HER2-Positive Advanced or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT03650348
- Acronym / sponsor ID
- PRS-343-PCS_08_18
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Pieris Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 21 Aug 2018 (actual)
- Primary completion
- 11 Aug 2022 (actual)
- Study completion
- 11 Aug 2022 (actual)
- First posted
- 28 Aug 2018 (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 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single Group Assignment Drug PRS-343 Combination Therapy
| Arm | Type | Receives |
|---|---|---|
| PRS-343 in Combination with Atezolizumab | Experimental | Drug: PRS-343 in Combination with Atezolizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (27 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-343 in Combination with AtezolizumabHER2/4-1BB Bispecific | Drug | PRS-343 in Combination with Atezolizumab |
Primary outcome
Incidence of DLTs and recommended Phase 2 dose (RP2D) of PRS-343 administered in combination with atezolizumab
Time frame: Up to 36 months
9 secondary outcomes
Overall response rate (ORR) per RECIST v1.1
Time frame: Up to 36 months
Duration of response (DOR) per RECIST v1.1
Time frame: Up to 36 months
Rate of complete response (CR) per RECIST v1.1
Time frame: 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
Time frame: Up to 36 months
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
Presence and/or concentration of anti-PRS-343 and anti-atezolizumab antibodies (anti-drug antibodies [ADAs])
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
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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.
8 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 Combination with Atezolizumab in people with HER2-positive Breast Cancer and HER2-positive Gastric Cancer, run by Pieris Pharmaceuticals, Inc. at 8 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 20 inclusion and 27 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 8 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 of DLTs and recommended Phase 2 dose (RP2D) of PRS-343 administered in combination with atezolizumab (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.