CYNK-101 in Combination with Trastuzumab and Pembrolizumab in Patients with Locally Advanced Unresectable or Metastatic HER2-Positive Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma
NCT ID: NCT05207722
Last Updated: 2024-12-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE1/PHASE2
1 participants
INTERVENTIONAL
2022-04-14
2024-02-15
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Phase I Dose Escalation
Up to two dosing cohorts of CYNK-101 in combination with rhIL2 will be evaluated following an initial induction and lymphodepletion regimen.
CYNK-101
CYNK-101 is a human placental hematopoietic stem/progenitor cell derived NK cell product, that is genetically modified to express a variant of CD16, Fc gamma receptor III (FcγRIII).
Pembrolizumab
200 mg on Day 1 of each 3-week cycle as an IV infusion.
Trastuzumab
8 mg/kg loading dose and then 6 mg/kg maintenance dose administered IV on day 1 of each 3-week cycle.
Recombinant Human Interleukin-2
6 million (M) international units (IU) of rhIL-2 administered subcutaneously (SC) on each CYNK-101 infusion day.
Cyclophosphamide
Cyclophosphamide: 900 mg/m2 administered IV as part of a 3-day lymphodepletion regimen.
Fludarabine
Fludarabine: 30 mg/m2 administered IV as part of a 3-day lymphodepletion regimen.
Mesna
MESNA: shall be administered as part of a 3-day lymphodepletion regimen for the inhibition of hemorrhagic cystitis induced by cyclophosphamide. Route of administration, dosage, and frequency of Mesna should be based on institutional standards.
Phase IIa Expansion
Once the Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) is determined in Phase I, the Phase IIa portion of the study will commence.
CYNK-101
CYNK-101 is a human placental hematopoietic stem/progenitor cell derived NK cell product, that is genetically modified to express a variant of CD16, Fc gamma receptor III (FcγRIII).
Pembrolizumab
200 mg on Day 1 of each 3-week cycle as an IV infusion.
Trastuzumab
8 mg/kg loading dose and then 6 mg/kg maintenance dose administered IV on day 1 of each 3-week cycle.
Recombinant Human Interleukin-2
6 million (M) international units (IU) of rhIL-2 administered subcutaneously (SC) on each CYNK-101 infusion day.
Cyclophosphamide
Cyclophosphamide: 900 mg/m2 administered IV as part of a 3-day lymphodepletion regimen.
Fludarabine
Fludarabine: 30 mg/m2 administered IV as part of a 3-day lymphodepletion regimen.
Mesna
MESNA: shall be administered as part of a 3-day lymphodepletion regimen for the inhibition of hemorrhagic cystitis induced by cyclophosphamide. Route of administration, dosage, and frequency of Mesna should be based on institutional standards.
Interventions
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CYNK-101
CYNK-101 is a human placental hematopoietic stem/progenitor cell derived NK cell product, that is genetically modified to express a variant of CD16, Fc gamma receptor III (FcγRIII).
Pembrolizumab
200 mg on Day 1 of each 3-week cycle as an IV infusion.
Trastuzumab
8 mg/kg loading dose and then 6 mg/kg maintenance dose administered IV on day 1 of each 3-week cycle.
Recombinant Human Interleukin-2
6 million (M) international units (IU) of rhIL-2 administered subcutaneously (SC) on each CYNK-101 infusion day.
Cyclophosphamide
Cyclophosphamide: 900 mg/m2 administered IV as part of a 3-day lymphodepletion regimen.
Fludarabine
Fludarabine: 30 mg/m2 administered IV as part of a 3-day lymphodepletion regimen.
Mesna
MESNA: shall be administered as part of a 3-day lymphodepletion regimen for the inhibition of hemorrhagic cystitis induced by cyclophosphamide. Route of administration, dosage, and frequency of Mesna should be based on institutional standards.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Have cytologically or histologically confirmed diagnosis for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-Positive Gastric or Gastroesophageal junction (G/GEJ) adenocarcinoma.
Exclusion Criteria
* HER2 overexpression is defined by immunohistochemistry (IHC) or in situ hybridization (ISH) for amplification of HER2 gene.
* Patients must have either IHC 3+ or IHC 2+ with a positive fluorescent in-situ hybridization (FISH) or FISH + alone, as assessed locally on primary or metastatic tumor.
* Due to differences in tumor histopathology, use of FDA-approved tests, specific for Gastric Cancers, will be required when assessing HER2 Expression \[HERCEPTIN package insert; 202120\].
4. Have measurable disease as assessed by the investigator according to RECIST 1.1 \[Eisenhauer EA et al, 200913\].
5. Have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) performance scale.
6. Have a life expectancy of ≥ 6 months.
7. Patients must agree to use a highly effective method of contraception from the start of the study until 1 year after the last dose of lymphodepletion or 4 months from last dose of pembrolizumab, or 6 months from last dose of trastuzumab; whichever comes later.
8. Have adequate cardiac function, defined as left ventricular ejection fraction \> 45% as determined by MUGA scan or ECHO and QT interval calculated according to the Fridericia method (≤ 470 ms for men and ≤480 ms for women).
9. Demonstrate adequate organ function by laboratory values as follows:
* Hematological:
* Absolute neutrophil count (ANC) ≥ 1.5 x 109/L,
* Platelet count ≥ 100 x 109/L
* Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
* Renal:
o Calculated creatinine clearance (Cockcroft-Gault Formula) ≥ 50 mL/min
* Hepatic:
o Total bilirubin ≤1.5 x ULN
* Exception: Patients with Gilbert's disease total bilirubin ≤ 3.0 x ULN
o Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
* Exception: AST and ALT ≤ 5 x ULN for patients with liver metastases.
* Coagulation:
* Prothrombin Time (PT) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy if PT or PTT is within therapeutic range of intended use of anticoagulants
* activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy if PT or PTT is within therapeutic range of intended use of anticoagulants
1. Patients who have received prior systemic therapy for locally advanced unresectable or metastatic disease.
2. Has had major surgery, open biopsy, or significant traumatic injury within 28 days prior to Visit 2, or anticipation of the need for major surgery during the course of study treatment.
3. Has had radiotherapy within 14 days prior to Visit 2.
4. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Exceptions: Squamous or Basal cell carcinoma of the skin, superficial bladder cancer, and prostate cancer not requiring treatment.
5. Patients with symptomatic, untreated, or actively progressing CNS metastases. Patients with a history of CNS metastases are eligible if they have not received radiotherapy within 7 days or whole-brain radiation for the past 14 days. Patients should not be receiving ongoing treatment with either corticosteroids or anticonvulsants. Patients with new CNS metastases detected during the Screening period, may participate in the study if they receive radiotherapy or surgery resulting in stable metastatic disease.
6. Has an active autoimmune disease that has required systemic treatment in the past 2 years.
7. Patients with hypothyroidism who are on stable replacement therapy will be allowed.
8. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy greater than 10 mg per day of prednisone or equivalent.
• Patients who require replacement for adrenal insufficiency will be allowed.
9. Has a history of (non-infectious) pneumonitis that requires steroids or current pneumonitis.
10. Has a known history of active tuberculosis.
11. Has an active infection requiring systemic therapy.
12. Accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 14 days prior to Visit 2. If the participant is receiving diuretic drugs for other reasons, it is acceptable.
13. Has peripheral neuropathy \> Grade 1.
14. Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial.
15. Has active or clinically significant cardiac disease including:
* History of myocarditis
* History or presence of serious uncontrolled cardiac arrhythmias.
* Clinically significant resting bradycardia.
* Left ventricular ejection fraction (LVEF) as determined by echocardiogram (ECHO) \< 45% or multiple gated acquisition scan (MUGA) \< 45%.
* Any of the following within 6 months prior to the start of the study treatments:
myocardial infarction (MI), severe/unstable angina, congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic attack (TIA).
16. Patients with history of human immunodeficiency virus (HIV) infection must be seronegative.
17. Known active infection with hepatitis B, hepatitis C, SARS-CoV-2, or other viral infections requiring systemic therapy.
18. Patients having a potential hypersensitivity (≥ Grade 3) to pembrolizumab, trastuzumab, study chemotherapy agents, rhIL-2 and/or to any excipients, murine proteins, or platinum-containing products. NOTE: any adverse events which has occurred because of prior therapy MUST have resolved to ≤ Grade 1 according to CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5 prior to study entry.
19. Has had an allogeneic tissue/solid organ transplant.
20. Immunized with live vaccine ≤ 28 days before Visit 2.
21. Participation in study of investigational agent or device ≤ 28 day prior to Visit 2.
22. Patient is pregnant or breastfeeding.
18 Years
75 Years
ALL
No
Sponsors
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Celularity Incorporated
INDUSTRY
Responsible Party
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Principal Investigators
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Adrian Kilcoyne, MD
Role: STUDY_DIRECTOR
Celularity Incorporated
Locations
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Scripps Health
La Jolla, California, United States
Georgetown
Washington D.C., District of Columbia, United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States
Countries
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Other Identifiers
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CYNK-101-HER2-001
Identifier Type: -
Identifier Source: org_study_id