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HER2-positive Gastric CancerPhase 2NCT05190445

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

A Phase 2 study testing Cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxel and Cinrebafusp alfa (PRS-343) in combination with tucatinib in people with HER2-positive Gastric Cancer, run by Pieris Pharmaceuticals, Inc. at 5 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HER2-positive Gastric Cancer
What is being tested?
Cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxel and Cinrebafusp alfa (PRS-343) in combination with tucatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
5 sitesin 2 countries
Study dates
1 Nov 2021to 1 Feb 2023
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 of age
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
  • Histologically or cytologically confirmed gastric or GEJ adenocarcinoma
  • 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
  • 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
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  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • 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.
  • Left ventricular ejection fraction (LVEF) of ≥ 50% as determined by echocardiogram or multigated acquisition scan
  • Resolution to Grade ≤1 by NCI CTCAE v5.0 of all clinically significant toxicities associated with prior therapy or procedures
  • 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
  • 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

Who cannot join

  • Disease of squamous or undifferentiated histology
  • 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
  • Arm 1 only: Receipt of any previous systemic therapy (including investigational agents) targeting the VEGF or the VEGFR signaling pathways
  • Intolerance to trastuzumab or other HER2-directed agent in prior treatment regimen
  • 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.
  • 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
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  • Significant bleeding disorders, vasculitis or a significant bleeding episode from the GI tract within 3 months prior to study entry
  • Arterial thromboembolic event within 6 months prior to study entry
  • 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 or symptomatic or poorly controlled cardiac arrhythmia
  • History of ejection fraction drop below the lower limit of normal with trastuzumab or other HER2-directed therapy
  • 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
  • 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
  • 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
  • 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)
  • 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)
  • Arm 2 only: Inability to swallow pills or presence of any significant gastrointestinal disease which would preclude the adequate absorption of an oral medication.
  • 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.
  • 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)
  • 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
  • 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
  • Arm 2 only: Prior anthracycline exposure (epirubicin > 720 mg/m2)
  • 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.
  • Active human immunodeficiency virus (HIV) disease, hepatitis B, or hepatitis C
  • Any severe infection within 28 days prior to study start or requirement for oral or intravenous antibiotics within 14 days prior to study start
  • 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.
  • 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
  • History of severe hypersensitivity reactions to monoclonal antibodies or Grade ≥3 immune-mediated adverse reaction to immune checkpoint inhibitor agents
  • 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
  • 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
  • Prior organ transplantation including allogeneic or autologous stem cell transplantation
  • Arm 2 only: Prior receipt of HER2-directed and/or EGFR-directed tyrosine kinase inhibitor (TKI) agents
  • 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
  • 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
  • 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
  • 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
  • Concurrent enrollment in another therapeutic clinical study
  • 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)

Trial locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

United States4 sites

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Sansum Clinic

    Santa Barbara, California, 93105

  • Maryland Oncology-Hematology

    Silver Spring, Maryland, 20904

Other trials in United States

South Korea1 site

  • Samsung Medical Center

    Seoul

Other trials in South Korea

About this study

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

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.

Read the 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).

Being tested
Cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxel, Cinrebafusp alfa (PRS-343) in combination with tucatinib
Keywords
HER2-positive gastric cancer, HER2-positive gastroesophageal junction, HER2-positive GEJ, Pieris, PRS-343, cinrebafusp alfa, ramucirumab, paclitaxel, anticalin protein, bispecific, 4-1BB, CD137, CD8+ T cell, HER2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxelDrug

    HER2/4-1BB

  • Cinrebafusp alfa (PRS-343) in combination with tucatinibDrug

    HER2/4-1BB

Study groups in NCT05190445
Study groupRoleWhat they receive
Cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxelExperimentalPatients 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
Receives: Drug: Cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxel
Cinrebafusp alfa (PRS-343) in combination with tucatinibExperimentalPatients 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
Receives: Drug: Cinrebafusp alfa (PRS-343) in combination with tucatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate (ORR) as defined by RECIST v1.1

    Measured: Up to 18 months

Secondary outcomes (6)

  1. Progression-free survival (PFS)

    Measured: Up to 18 months

  2. Disease control rate (DCR, CR+PR+SD)

    Measured: Up to 18 months

  3. Duration of response (DOR)

    Measured: Up to 18 months

  4. Time to progression (TTP)

    Measured: Up to 18 months

  5. Overall survival (OS)

    Measured: Up to 18 months

  6. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Measured: Up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2022
  2. Study start1 Nov 2021
  3. Primary completion1 Feb 2023 (estimated)
  4. Study completion1 Feb 2023 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Parallel Group Assignment Drug Cinrebafusp Alfa (PRS-343) Combination Therapy
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05190445
Sponsor's protocol ID
PRS-343-PCS_09_20
Status last verified
Sep 2022
First submitted
19 Jul 2021
Last updated
8 Sep 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxel and Cinrebafusp alfa (PRS-343) in combination with tucatinib in people with HER2-positive Gastric Cancer, run by Pieris Pharmaceuticals, Inc. at 5 sites in 2 countries.

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 21 inclusion and 43 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: under way, not looking for participants, as of the sponsor's last update on 8 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, South Korea. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Overall response rate (ORR) as defined by RECIST v1.1 (time frame: Up to 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05190445.

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 8 Sep 2022.

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