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

NCT05190445 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: PRS-343-PCS_09_20
• Study Type: interventional
• Target: 80
• Locations: 2 countries
• Sites: 5

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.

Conditions

HER2-positive Gastric Cancer

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

Outcome Measures

Primary Outcomes (1)

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

  Up to 18 months

Secondary Outcomes (6)

• Progression-free survival (PFS)

  Up to 18 months

• Disease control rate (DCR, CR+PR+SD)

  Up to 18 months

• Duration of response (DOR)

  Up to 18 months

• Time to progression (TTP)

  Up to 18 months

• Overall survival (OS)

  Up to 18 months

Other Outcomes (8)

• Evaluation of soluble 4 1BB levels and HER2 amplification in cell-free circulating tumor DNA (ctDNA) isolated from plasma

  Up to 18 months

• 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

  Up to 18 months

• Cmax f cinrebafusp alfa in Cycles 1 and 2

  Up to 18 months

Study Arms (2)

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

EXPERIMENTAL

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

Cinrebafusp alfa (PRS-343) in combination with tucatinib

EXPERIMENTAL

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

Interventions

Cinrebafusp alfa (PRS-343) in combination with ramucirumab and paclitaxel DRUG

HER2/4-1BB

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

Cinrebafusp alfa (PRS-343) in combination with tucatinib DRUG

HER2/4-1BB

Cinrebafusp alfa (PRS-343) in combination with tucatinib

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 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
• 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

You may not qualify if:

• 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
• 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
• 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)

Sponsors & Collaborators

• Pieris Pharmaceuticals, Inc.: lead

Study Sites (5)

Sansum Clinic

Santa Barbara, California, 93105, United States

Location

Maryland Oncology-Hematology

Silver Spring, Maryland, 20904, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Samsung Medical Center

Seoul, South Korea

Location

MeSH Terms

Interventions

Ramucirumab; Paclitaxel; tucatinib

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Gordon Otto, MD, PhD

  Pieris Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel Group Assignment Drug Cinrebafusp Alfa (PRS-343) Combination Therapy

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: January 13, 2022
• Study Start: November 1, 2021
• Primary Completion: February 1, 2023
• Study Completion: February 1, 2023
• Last Updated: September 8, 2022

Record last verified: 2022-09

Locations

KR (1); US (4)