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

NCT02879760 | Completed Phase 1

• 1 other identifier: Ad/MG1-MAGEA3-001 (Sandpiper)
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 6

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 at least 1 cycle of platinum based chemotherapy and/or at least one treatment of PD-1 or PD-L1 antibody targeted therapy.

Conditions

Non-Small Cell Lung Cancer

Keywords

Lung; Cancer; Chemotherapy; Oncolytic virus; Immunotherapy; Pembrolizumab; Keytruda

Outcome Measures

Primary Outcomes (2)

• Phase 1 - Toxicity as measured by adverse events

  To determine the maximum tolerated dose MTD/ maximum feasible dose MFD of Ad/MAGEA3 and MG1-MAGEA3 in combination with pembrolizumab

  7 months

• Phase 2 - Objective tumour response rate (ORR) based on RECIST v1.1

  To evaluate objective tumour response rate (ORR) based on RECIST 1.1

  7 months

Study Arms (1)

Ad/MAGEA3, MG1-MAGEA3 and pembrolizumab

EXPERIMENTAL

Ad-MAGEA3 prime will be administered as a single IM dose on Day 1 at 2 x 10e11 VP. MG1/MAGEA3 boost will be administered IV on Day 15 and Day 18 by 5 cohorts: Cohort 1: Days 15 \& 18 at 1x 10e10 pfu. Cohort 2: Days 15 \& 18 at 1x 10e11 pfu. Cohort 3: Day 15 at 1 x 10e11 pfu; Day 18 at 3 x 10e11 pfu. Cohort 4: Day 15 at 1 x 10e11 pfu; Day 18 at 3 x 10e11 pfu. Cohort 5: Day 15 at 3x 10e11 pfu; Day 18 at 3 x 10e12 pfu. Pembrolizumab will be administered IV every 3 weeks starting on Day 22.

Biological: Ad-MAGEA3; Biological: MG1-MAGEA3; Biological: Pembrolizumab

Interventions

Ad-MAGEA3 BIOLOGICAL

Intramuscular injection

Ad/MAGEA3, MG1-MAGEA3 and pembrolizumab

MG1-MAGEA3 BIOLOGICAL

Intravenous infusion

Ad/MAGEA3, MG1-MAGEA3 and pembrolizumab

Pembrolizumab BIOLOGICAL

Intravenous infusion

Ad/MAGEA3, MG1-MAGEA3 and pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible for participation in this trial, the patient must:
• Have histologically or cytologically confirmed diagnosis of NSCLC (squamous or non-squamous) with positive expression of MAGE-A3 (primary or metastatic lesion).
• Phase 1: Have radiographic progression after treatment with at least 1 cycle of platinum-doublet chemotherapy and/or at least one treatment of PD-1 or PD-L1 antibody targeted therapy. Adjuvant therapy will count as a regimen if administered within 1 year before relapse.
• Phase 2: Have radiographic progression during or after treatment with anti-PD-1/PD-L1 antibody. Adjuvant therapy will count as regimen if administered within 1 year before relapse.
• Phase 1: 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 the Phase 1 portion of the 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. 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.
• Phase 2: Patients with the above ALK and EGFR targetable mutations will not be eligible for treatment.
• 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 post irradiation treatment.
• Have at least one tumor amenable to biopsy.
• Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Demonstrate adequate organ function:
• White blood cell (WBC) count ≥3,000 cells/mm3
• Absolute neutrophil count (ANC) ≥1,000 cells/mm3
• Hemoglobin ≥8 g/dL or ≥4.96 mmol/L (correction with transfusion or erythropoietin-based therapy allowed to meet eligibility criteria)
• Platelet count ≥100,000 platelets/mm3 (untransfused)
• Total bilirubin ≤1.5 x Upper Limit of Normal (ULN) OR direct bilirubin ≤ULN for patients with total bilirubin levels \>1.5 x ULN (i.e., patients with Gilberts disease)

You may not qualify if:

• The patient must be excluded from participating in the trial if the patient:
• Has disease that is suitable for local therapy administered with curative intent.
• Has had prior treatment with any MAGE-A3 vaccine immunotherapy including Ad-MAGEA3 or MG1-MAGEA3.
• Is currently receiving experimental therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• 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.
• Has been intolerant of prior PD-1/PD-L1 targeted antibody therapy for which re-treatment would expose the patient to clinically significant risk in the opinion of the investigator (please attain sponsor permission of enrollment of any patient with prior intolerance to anti-PD-1/PD-L1 antibody treatment).
• 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 having any alopecia are an exception to this criterion and may qualify for the study.
• Note: If patient received major surgery, they must be at least 4 weeks from surgery AND have recovered adequately from the toxicity and/or complications from the surgery prior to starting therapy.
• Note: Patients receiving prior radiation must have recovered (\< Grade 1) from any acute toxicity. Patients having irreversible but not clinically significant toxicity are eligible.
• Note: Patients receiving prior lung radiation with a dose of \>30 Gy must wait at least 8 weeks from the date of completion of the lung radiation before the first dose of pembrolizumab.
• Has received prior treatment with vesicular stomatitis virus (VSV) based viral vector.
• Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended for per protocol biopsies as per standard of care.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Note: Patients with previously treated brain metastases who are stable may participate. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.

Sponsors & Collaborators

• Turnstone Biologics, Corp.: lead

Study Sites (6)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Moncton Hospital

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (2)

• Jenner AL, Cassidy T, Belaid K, Bourgeois-Daigneault MC, Craig M. In silico trials predict that combination strategies for enhancing vesicular stomatitis oncolytic virus are determined by tumor aggressivity. J Immunother Cancer. 2021 Feb;9(2):e001387. doi: 10.1136/jitc-2020-001387.

  PMID: 33608375 DERIVED

• Pol JG, Acuna SA, Yadollahi B, Tang N, Stephenson KB, Atherton MJ, Hanwell D, El-Warrak A, Goldstein A, Moloo B, Turner PV, Lopez R, LaFrance S, Evelegh C, Denisova G, Parsons R, Millar J, Stoll G, Martin CG, Pomoransky J, Breitbach CJ, Bramson JL, Bell JC, Wan Y, Stojdl DF, Lichty BD, McCart JA. Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic Maraba virus currently in first-in-human trials. Oncoimmunology. 2018 Sep 19;8(1):e1512329. doi: 10.1080/2162402X.2018.1512329. eCollection 2019.

  PMID: 30546947 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Caroline Breitbach, PhD

  Turnstone Biologics, Corp.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2016
• First Posted: August 26, 2016
• Study Start: March 8, 2017
• Primary Completion: February 15, 2020
• Study Completion: May 24, 2020
• Last Updated: October 6, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (6)