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Trial record 3 of 3 for:    PRS-343

Cinrebafusp Alfa in Combination With Ramucirumab and Paclitaxel in HER2-High Gastric or GEJ Adenocarcinoma and in Combination With Tucatinib in HER2-Low Gastric or GEJ Andenocarinoma

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ClinicalTrials.gov Identifier: NCT05190445
Recruitment Status : Recruiting
First Posted : January 13, 2022
Last Update Posted : January 18, 2022
Sponsor:
Information provided by (Responsible Party):
Pieris Pharmaceuticals, Inc.

Brief Summary:
A Phase 2, multi-center, open-label study of cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxel in patients with HER2-high and in combination with tucatanib in patients with HER2-low gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Condition or disease Intervention/treatment Phase
HER2-positive Gastric Cancer Drug: Cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxel Drug: Cinrebafusp alfa (PRS-343) in combination with tucatinib Phase 2

Detailed Description:
This is a multi-center, open-label study of cinrebafusp alfa in combination with clinically established doses of ramucirumab and paclitaxel in patients with HER2-positive (IHC 3+ or IHC 2+ with HER2/neu gene amplification) gastric or GEJ adenocarcinoma (Arm 1) and in combination with tucatinib in patients with low levels of HER2 (IHC 1+ or IHC 2+ without HER2/neu amplification) (Arm 2).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel Group Assignment Drug Cinrebafusp Alfa (PRS-343) Combination Therapy
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multi-Center, Open-Label Study of Cinrebafusp Alfa (PRS-343) in Combination With Ramucirumab and Paclitaxel in Patients With HER2-Positive Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma and in Combination With Tucatinib in Patients With HER2 Low Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Actual Study Start Date : November 1, 2021
Estimated Primary Completion Date : February 1, 2023
Estimated Study Completion Date : February 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxel
Patients aged 18 years or older with HER2-positive gastric or GEJ adenocarcinoma who have progressed on prior treatment with a regimen containing a platinum and fluoropyrimidine and a HER2-directed therapy such as trastuzumab and now are candidates for treatment with ramucirumab and paclitaxel
Drug: Cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxel
HER2/4-1BB

Experimental: Cinrebafusp alfa (PRS-343) in combination with tucatinib
Patients aged 18 years or older with HER2 low (IHC 1+ or IHC 2+ without HER2/neu amplification) gastric or GEJ adenocarcinoma who have received at least one prior treatment regimen
Drug: Cinrebafusp alfa (PRS-343) in combination with tucatinib
HER2/4-1BB




Primary Outcome Measures :
  1. Overall response rate (ORR) as defined by RECIST v1.1 [ Time Frame: Up to 18 months ]

Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Up to 18 months ]
  2. Disease control rate (DCR, CR+PR+SD) [ Time Frame: Up to 18 months ]
  3. Duration of response (DOR) [ Time Frame: Up to 18 months ]
  4. Time to progression (TTP) [ Time Frame: Up to 18 months ]
  5. Overall survival (OS) [ Time Frame: Up to 18 months ]
  6. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: Up to 18 months ]

Other Outcome Measures:
  1. Evaluation of soluble 4 1BB levels and HER2 amplification in cell-free circulating tumor DNA (ctDNA) isolated from plasma [ Time Frame: Up to 18 months ]
  2. Immunohistochemical analysis of HER2, PD-L1, CD8, Ki-67, GrzB and other relevant markers and molecules that may be found to be relevant during the course of this investigation in tumor tissue [ Time Frame: Up to 18 months ]
  3. Cmax f cinrebafusp alfa in Cycles 1 and 2 [ Time Frame: Up to 18 months ]
  4. AUC0-tlast of cinrebafusp alfa in Cycles 1 and 2 [ Time Frame: Up to 18 months ]
  5. Ramucirumab concentration after exposure to cinrebafusp alfa [ Time Frame: Up to 18 months ]
  6. Evaluate cinrebafusp alfa drug concentration in serum [ Time Frame: Up to 18 months ]
  7. Compare levels of HER2 and HER2 gene amplification in an archival tissue specimen and in a tumor biopsy specimen collected after completion of prior HER2-directed therapy [ Time Frame: Up to 18 months ]
  8. Compare levels of HER2 protein expression and/or gene amplification and HER2 gene amplification in ctDNA isolated before treatment initiation with clinical benefit derived from study treatment [ Time Frame: Up to 18 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed written informed consent obtained prior to performing any study procedure, including screening procedures
  2. Men and women ≥18 years of age
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
  4. Histologically or cytologically confirmed gastric or GEJ adenocarcinoma
  5. Arm 1: Has received no more than two prior treatment regimens for advanced disease, including a platinum, a fluoropyrimidine, and HER2-directed therapy such as trastuzumab Arm 2: Has received at least one prior treatment regimen for advanced disease
  6. Arm 1: Demonstration of HER2 positivity assessed by a test with appropriate regulatory validation in a current tissue specimen and following guidelines for assessment in gastric or GEJ adenocarcinoma described in Section 4.3 after receiving no more than two prior treatment regimens, including a platinum, a fluoropyrimidine, and HER2-directed therapy such as trastuzumab Arm 2: Demonstration of HER2 IHC 1+ or IHC 2+ without HER2/neu amplification assessed by a test with appropriate regulatory validation in a current tissue specimen and following guidelines for assessment in gastric or GEJ adenocarcinoma described in Section 4.3 after completion of the most recent prior treatment regimen
  7. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  8. Adequate organ and hematologic function as defined below:

    • Serum AST and ALT ≤2.5 × upper limit of normal (ULN) or ≤5 × ULN in the presence of liver metastases
    • Total serum bilirubin ≤1.5 × ULN
    • Serum albumin ≥ 3g/dL
    • Serum creatinine ≤1.5 × ULN OR creatinine clearance measured via 24-hour urine collection ≥40 mL/min if serum creatinine is > 1.5X ULN
    • Arm 1 only: Urinary protein is ≤ 1+ on dipstick or routine urine analysis; if urine dipstick or urinalysis is ≥ 2+, a 24-hour urine collection for protein must demonstrate < 1000 mg of protein in 24 hours
    • Hemoglobin ≥ 9 g/dL; packed red blood cell transfusions are not allowed in the week preceding screening evaluation
    • ANC ≥ 1500/mm3
    • Platelet count ≥ 100,000/mm3
    • INR ≤1.5 and PT ≤1.5 × ULN and PTT ≤1.5 × ULN. Arm 1 only: Patients receiving oral anti-coagulants must be switched to low molecular weight anti-coagulants and have achieved stable coagulation profile prior to first dose of protocol therapy. Arm 2 only: Patients receiving oral anti-coagulants must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy.
  9. Left ventricular ejection fraction (LVEF) of ≥ 50% as determined by echocardiogram or multigated acquisition scan
  10. Resolution to Grade ≤1 by NCI CTCAE v5.0 of all clinically significant toxicities associated with prior therapy or procedures
  11. If sexually active, the patient must be post-menopausal, surgically sterile or using highly effective contraception. Highly effective contraception for women of child-bearing potential and males with female partners of child-bearing potential is defined as 1 barrier method (e.g., condom) and 1 additional method (e.g., hormonal) of contraception during the study and for at least three months from the last study treatment or recommended contraceptive period according to the local label of the concomitant drug if greater than 3 months
  12. Women of child-bearing potential may not be breastfeeding and must have a negative serum pregnancy test within 96 hours prior to start of study treatment

Exclusion Criteria:

  1. Disease of squamous or undifferentiated histology
  2. History or evidence of known active CNS metastases or carcinomatous meningitis. Patients with brain metastases are eligible provided they have shown clinical and radiographic stable disease for at least 4 weeks after definitive therapy and have not used steroids (> 10 mg/day of prednisone or equivalent) for at least 2 weeks prior to the first dose of study treatment
  3. Arm 1 only: Receipt of any previous systemic therapy (including investigational agents) targeting the VEGF or the VEGFR signaling pathways
  4. Intolerance to trastuzumab or other HER2-directed agent in prior treatment regimen
  5. History of deep vein thrombosis (DVT), pulmonary embolism (PE) or any other significant thromboembolism during the three months prior to first dose of study treatment; venous port or catheter thrombosis or superficial venous thrombosis are not considered significant (Arm 1 only). For patients in Arm 2, the investigator is referred to Exclusion Criterion 21 and should consult with the Medical Monitor in the case of a history of these or similar events.
  6. Chronic therapy with nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., indomethacin, ibuprofen, naproxen or similar agents) or other antiplatelet agents (e.g., clopidogrel, ticlopidine, dipyridamole, anagrelide); aspirin up to 325 mg per day is permitted
  7. Significant bleeding disorders, vasculitis or a significant bleeding episode from the GI tract within 3 months prior to study entry
  8. Arterial thromboembolic event within 6 months prior to study entry
  9. History of acute coronary syndromes, including myocardial infarction, coronary artery bypass graft, unstable angina, coronary angioplasty or stenting within past 24 weeks
  10. History of or current Class II, III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system or symptomatic or poorly controlled cardiac arrhythmia
  11. History of ejection fraction drop below the lower limit of normal with trastuzumab or other HER2-directed therapy
  12. Uncontrolled or poorly-controlled hypertension (arterial hypertension ≥150 mm Hg or diastolic ≥90 mmHg) for > four weeks despite standard medical management; the patient may be re-screening after treatment for hypertension
  13. Any arterial thromboembolic event, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident or unstable angina, within six months prior to first dose of study treatment
  14. Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis or chronic diarrhea
  15. Gastrointestinal perforation or fistula within 6 months prior to study entry or have risk factors for perforation (these events may be acceptable for patients enrolled in Arm 2 after discussion with the Medical Monitor)
  16. Grade 3 or Grade 4 GI bleeding within 3 months prior to first study treatment (these events may be acceptable for patients enrolled in Arm 2 after discussion with the Medical Monitor)
  17. Arm 2 only: Inability to swallow pills or presence of any significant gastrointestinal disease which would preclude the adequate absorption of an oral medication.
  18. Cirrhosis at a level of Child-Pugh B or worse OR cirrhosis of any degree and a history of hepatic encephalopathy or hepatorenal syndrome or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful cirrhosis is defined as ascites from cirrhosis requiring diuretics or paracentesis.
  19. Serious or non-healing wound, ulcer or bone fracture within 28 days prior to first study treatment (these events may be acceptable for patients enrolled in Arm 2 after discussion with the Medical Monitor)
  20. Any medical, psychiatric, cognitive or other condition that compromises the patient's ability to understand information, to give informed consent or to comply with the study protocol
  21. Any severe concurrent disease or condition (including active infection, cardiac arrhythmia, interstitial lung disease) that in the judgment of the Investigator would make study participation inappropriate for the patient
  22. Arm 2 only: Prior anthracycline exposure (epirubicin > 720 mg/m2)
  23. Arm 2 only: Having used a strong cytochrome P450 CYP2C8 inhibitor within three elimination half-lives of the inhibitor or have used a strong CYP3A4 or moderate/strong CYP2C8 inducer within five days prior to first dose of study treatment. Patients on the strong CYP2C8 inhibitor gemfibrozil at screening must discontinue its use at least 24 hours before the first dose of study drug and if needed, substitute an alternate lipid-lowering agent.
  24. Active human immunodeficiency virus (HIV) disease, hepatitis B, or hepatitis C
  25. Any severe infection within 28 days prior to study start or requirement for oral or intravenous antibiotics within 14 days prior to study start
  26. Administration of live attenuated vaccines within 28 days prior to start of treatment or anticipated need for vaccination with live attenuated vaccine during the study. Vaccination for SARS-CoV-2 is permitted:

    • Patients in screening, who have not started study treatment, and who are receiving a two-dose vaccine should schedule their vaccination(s) to receive the second dose at least two weeks prior to initiation of treatment (Cycle 1, Day 1).
    • If the patient is receiving a single-dose vaccine, the single dose should be at least two weeks prior to initiation of treatment (Cycle 1, Day 1).
    • Vaccination during Cycle 1 between the first and the second cycle of cinrebafusp alfa is discouraged.
    • Beginning with Cycle 2 a minimum of 7 days must elapse from last study treatment to administration of vaccine and patients must have seven days elapse from vaccination to next treatment on study.
    • Efforts should be made to avoid treatment delays, but where necessary a delay of up to seven days in next treatment of the study drug will be permitted.
  27. History of infusion or other reactions to any components/excipients of cinrebafusp alfa (Arm 1 and Arm 2), or ramucirumab or paclitaxel (Arm 1); Arm 2 only: history of allergic reactions to tucatinib or compounds chemically or biologically similar to tucatinib, or known allergy to any of the excipients in tucatinib
  28. History of severe hypersensitivity reactions to monoclonal antibodies or Grade ≥3 immune-mediated adverse reaction to immune checkpoint inhibitor agents
  29. 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; topical, inhaled, nasal and ophthalmic steroids are not prohibited
  30. History of autoimmune disease that has required systemic treatment with disease-modifying agents, corticosteroids, or immunosuppressive drugs unless in the opinion of the investigator the patient is in a complete and durable remission; physiologic replacement therapies, such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, is allowed
  31. Prior organ transplantation including allogeneic or autologous stem cell transplantation
  32. Arm 2 only: Prior receipt of HER2-directed and/or EGFR-directed tyrosine kinase inhibitor (TKI) agents
  33. Concurrent or previous other malignancy within 3 years of study entry with the exception of cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intra-epithelial neoplasm, carcinoma in situ of the cervix, or other non-invasive or indolent malignancy
  34. Receipt of an investigational agent, chemotherapy or other cancer-directed therapy within 4 weeks (6 weeks for nitrosoureas and mitomycin C) of initiation of study treatment
  35. Receipt of radiation therapy within 4 weeks of scheduled Day 1 dosing, unless the radiation comprised a limited field to non-visceral structures; palliative radiotherapy is permitted
  36. Receipt of trastuzumab or adotrastuzumab emtansine or any other commercial or experimental drug that engages the same epitope as trastuzumab within 4 weeks of scheduled C1D1 dosing
  37. Concurrent enrollment in another therapeutic clinical study
  38. Major surgery within 28 days of scheduled C1D1 dosing or minor surgery or subcutaneous venous access device placement within 7 days prior to initiation of study treatment or elective or planned major surgery to be performed during the course of the clinical trial (these events may be acceptable for patients enrolled in Arm 2 after discussion with the Medical Monitor)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05190445


Contacts
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Contact: Kayti Aviano +1-857-246-8287 aviano@pieris.com
Contact: M. Jen Tsung +1-857-246-8287 tsung@pieris.com

Locations
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United States, California
Sansum Clinic Recruiting
Santa Barbara, California, United States, 93105
Contact: Heidi Keitkamp       hheitkam@ridleytreecc.org   
Contact: Megan Martinez       mwingo@ridleytreecc.org   
Principal Investigator: Mukul Gupta, MD         
United States, Maryland
Maryland Oncology-Hematology Recruiting
Silver Spring, Maryland, United States, 20904
Contact: Missy Almand    443-846-4563    missy.almand@usoncology.com   
Principal Investigator: Kashif Ali, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Amin Yaqubie       yaqubiea@mskcc.org   
Principal Investigator: Geoffrey Ku, MD         
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Melissa Shorter       mkshorter@mdanderson.org   
Contact: Wen Xiong    7137453029    wxiong1@mdanderson.org   
Principal Investigator: Sarina A Piha-Paul, MD         
Sub-Investigator: Jaffer Ajani, MD         
Sponsors and Collaborators
Pieris Pharmaceuticals, Inc.
Investigators
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Study Director: Tim Demuth, MD, PhD Pieris Pharmaceuticals, Inc.
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Responsible Party: Pieris Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT05190445    
Other Study ID Numbers: PRS-343-PCS_09_20
First Posted: January 13, 2022    Key Record Dates
Last Update Posted: January 18, 2022
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pieris Pharmaceuticals, Inc.:
PRS-343
HER2-positive gastric cancer
HER2-positive gastroesophageal junction
HER2-positive GEJ
Pieris
cinrebafusp alfa
ramucirumab
paclitaxel
anticalin protein
bispecific
4-1BB
CD137
CD8+ T cell
HER2
Additional relevant MeSH terms:
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Adenocarcinoma
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Paclitaxel
Ramucirumab
Tucatinib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors