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Trial record 2 of 2 for:    Recruiting Studies | maraba

Oncolytic MG1-MAGEA3 With Ad-MAGEA3 Vaccine in Combination With Pembrolizumab for Non-Small Cell Lung Cancer Patients

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ClinicalTrials.gov Identifier: NCT02879760
Recruitment Status : Recruiting
First Posted : August 26, 2016
Last Update Posted : September 5, 2017
Chiltern International Inc.
Information provided by (Responsible Party):
Turnstone Biologics, Inc.

Brief Summary:
This is a Phase 1/2, multi-center, open-label, dose-escalation trial of Ad-MAGEA3 and MG1-MAGEA3 in combination with pembrolizumab in patients with Non-Small Cell Lung Cancer who have completed a first standard therapy with an platinum based chemotherapy.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Biological: Ad-MAGEA3 Biological: MG1-MAGEA3 Biological: Pembrolizumab Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 61 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Trial of MG1 Maraba Expressing MAGE-A3 (MG1-MAGEA3), With Adenovirus Vaccine Expressing MAGE-A3 (Ad-MAGEA3), in Combination With Pembrolizumab in Patients With Previously Treated Metastatic Non-Small Cell Lung Cancer (NSCLC)
Actual Study Start Date : March 8, 2017
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Ad/MAGEA3, MG1-MAGEA3 and pembrolizumab

Ad/MAGEA3 prime will be administered as a single IM dose on Day 1 at 1e10 pfu. MG1/MAGEA3 boost will be administered IV on Day 15 and Day 18 by 4 cohorts: Cohort 1: Days 15 & 18 at 1e10 pfu.

Cohort 2: Days 15 & 18 at 1e11 pfu. Cohort 3: Day 15 at 1e11 pfu; Day 18 at 3e11 pfu. Cohort 4: Day 15 at 1e11 pfu; Day 18 at 1e12 pfu Pembrolizumab will be administered IV every 3 weeks starting on Day 1.

Biological: Ad-MAGEA3
Intramuscular injection
Biological: MG1-MAGEA3
Intravenous infusion
Biological: Pembrolizumab
Intravenous infusion

Primary Outcome Measures :
  1. Phase 1 - Toxicity as measured by adverse events [ Time Frame: 7 months ]
    To determine the maximum tolerated dose MTD/ maximum feasible dose MFD of Ad/MAGEA3 and MG1-MAGEA3 in combination with pembrolizumab

  2. Phase 2 - Objective tumour response rate (ORR) based on RECIST v1.1 [ Time Frame: 7 months ]
    To evaluate objective tumour response rate (ORR) based on RECIST 1.1

Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Have histologically or cytologically confirmed diagnosis of NSCLC (squamous or non-squamous) with positive expression of MAGE-A3 (primary or metastatic lesion).
  2. Have radiographic progression after treatment of at least 1 cycle of platinum-doublet chemotherapy. Adjuvant therapy will count as regimen if administered within 1 year before relapse.
  3. Patients with tumors of non-squamous NSCLC histology that have a known epidermal growth factor receptor (EGFR) mutation and/or anaplastic lymphoma kinase (ALK) translocation can participate in this study if they have failed the appropriate tyrosine kinase inhibitor (TKI) (intolerance or documented progression of their NSCLC) and have documented progression of their NSCLC on platinum doublet chemotherapy. There is no preferred order of treatment with TKI or platinum doublet therapy. If a patient is found to have one molecular alteration (either sensitizing EGFR mutation or ALK translocation), then testing for the other alteration is not required.
  4. Have measurable disease based on RECIST v1.1 criteria as determined by the site study team. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  5. Have at least one tumor amenable to biopsy. If a patient does not have a safely accessible tumor for biopsy, study entry requires permission from the sponsor.
  6. Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  7. Demonstrate adequate organ function:

    1. White blood cell (WBC) count ≥3,000 cells/mm3
    2. Absolute neutrophil count (ANC) ≥1,500 cells/mm3
    3. Hemoglobin ≥9 g/dL or ≥5.6 mmol/L
    4. Platelet count ≥100,000 platelets/mm3
    5. Total bilirubin ≤1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ULN for patients with total bilirubin levels >1.5 x ULN
    6. Aspartate transaminase (AST), alanine aminotransferase (ALT) ≤2.5 x ULN; ≤5.0 x ULN if patient has liver metastases
    7. Serum chemistries sodium, potassium, and calcium within normal limits (WNL) or Grade 1
    8. Serum creatinine ≤1.5 x ULN or creatinine clearance ≥60 mL/min for patient with creatinine levels >1.5 institutional ULN according to Cockcroft-Gault formula
    9. Serum phosphate >0.8 mmol/L (Grade 0-1)
    10. International normalized ratio (INR) ≤1.5 x ULN unless patient is receiving anticoagulant therapy as long as prothrombin time (PT) or partial prothrombin time (PTT) is within therapeutic range of intended use of anticoagulants
    11. Activated partial thromboplastin time (aPTT) ≤1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  8. Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  9. Female patients of childbearing potential (refer to Section 9.E.2.c) must be willing to use an adequate method of contraception as outlined in Section 9.E.2.c, starting on Day 1 through 120 days after the last dose of study medication.

    Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.

  10. Male patients of reproductive potential (Section 9.E.2.c) must agree to use an adequate method of contraception as outlined in Section 9.E.2.c, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

    Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.

  11. Be willing and able to provide written informed consent for the trial.
  12. Be 18 years of age (or legal age of majority in the jurisdiction) on day of signing informed consent.

Exclusion Criteria:

  1. Has disease that is suitable for local therapy administered with curative intent.
  2. Has had prior treatment with any anti-cancer immunotherapy, including therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or has previously participated in Merck MK-3475 clinical trials or who have had prior treatment with Ad-MAGEA3, MG1-MAGEA3, or any MAGE-A3 targeted therapy.
  3. Is currently receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of Day 1 dose of treatment.
  4. Has had prior anti-cancer monoclonal antibody (mAb) therapy within 4 weeks prior to study Day 1 or failure to recover (i.e., to ≤ Grade 1 or to baseline status) from adverse events (AEs) due to agents administered more than 4 weeks earlier.
  5. Has had prior chemotherapy, or targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ to Grade 1 or to baseline status) from AEs due to a previously administered agent.

    Note: Patients with ≤Grade 2 neuropathy or ≤Grade 2 alopecia are an exception to this criterion and may qualify for the study.

    Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

    Note: Patients receiving prior radiation must have recovered from any acute toxic effect unless Grade 1, irreversible and considered not clinically significant.

    Note: Patients receiving prior lung radiation with a dose of >30 Gy must wait at least 26 weeks from the date of completion of the lung radiation before the first dose of pembrolizumab.

  6. Has received prior treatment with vesicular stomatitis virus (VSV) based viral vector.
  7. Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended for per protocol biopsies as per standard of care.
  8. Has known active 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 [using the identical imaging modality for each assessment, either magnetic resonance imaging (MRI) or CT scan] for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 28 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.

  9. Has disease/tumor invading a major vascular structure (e.g., carotid artery), tumor related impending bowel obstruction or clinically significant and/or rapidly accumulating ascites, pericardial or pleural effusions.
  10. Has active autoimmune disease that has required systemic treatment in past 2 years (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 not considered a form of systemic treatment.
  11. Has evidence of active, non-infectious pneumonitis.
  12. Has a history of interstitial lung disease.
  13. Has an active infection requiring systemic therapy.
  14. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  15. Has used anti-viral medication, within 14 days of enrollment.
  16. Has conditions likely to have resulted in splenic dysfunction (e.g., splenectomy, sickle cell anemia, radiation to the spleen >20 Gy, congenital asplenism).
  17. Has significant immunodeficiency due to underlying illness (e.g., known HIV/AIDS) and/or medication (e.g., systemic corticosteroids) used immunosuppressive therapy within 4 weeks prior to the first dose of trial treatment.

    Note: Patients must not be receiving doses of >10 mg/day of prednisone or equivalent at the time of study entry and corticosteroids may not be used for premedication.

  18. Has uncontrolled pre-existing cardiovascular conditions and/or symptomatic cardiac dysfunction.
  19. Has >Grade 2 dyspnea and/or requirement for supplemental oxygen.
  20. Has received a live vaccine within 30 days of planned start of study therapy (Note: killed flu vaccine acceptable).

22. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.

22. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.

23. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

24. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting on Day 1 through 120 days after the last dose of trial treatment.

25. Has household contacts meeting any of the following criteria for study entry unless alternate living arrangements can be made:

a. Women who are pregnant or nursing an infant b. Children <12 months of age c. Individuals who are severely immunocompromised (including but not limited to bone-marrow or organ transplant recipients; individuals with Human Immunodeficiency virus {HIV} infection; individuals receiving chronic immunosuppressive medication).

26. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or Sponsor staff directly involved with this trial, unless prospective Research Ethics Board approval (by chair or designee) is given allowing exception to this criterion for a specific patient.

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): NCT02879760

Contact: Catherine Barker 613-421-8930 ext 245 catherine.barker@turnstonebio.com
Contact: Lesley Parker lesley.parker@turnstonebio.com

Canada, Ontario
Juravinski Cancer Centre Recruiting
Hamilton, Ontario, Canada, L8V 5C2
Contact: Rosalyn Juergens, MD    905-387-9711    juergensr@hhsc.ca   
Ottawa Hospital Research Institute Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Garth Nicholas, MD    613-737-7700    gnicholas@toh.ca   
University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Natasha Leighl, MD    416-946-4501    natasha.leighl@uhn.ca   
Sponsors and Collaborators
Turnstone Biologics, Inc.
Chiltern International Inc.
Study Director: Caroline Breitbach, PhD Turnstone Biologics, Inc.
Study Director: Lesley Parker Turnstone Biologics, Inc.

Responsible Party: Turnstone Biologics, Inc.
ClinicalTrials.gov Identifier: NCT02879760     History of Changes
Other Study ID Numbers: Ad/MG1-MAGEA3-001 (Sandpiper)
First Posted: August 26, 2016    Key Record Dates
Last Update Posted: September 5, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Turnstone Biologics, Inc.:
Oncolytic virus

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents