Phase 1/2 Study of Combination Immunotherapy and Messenger Ribonucleic Acid (mRNA) Vaccine in Subjects With NSCLC

NCT03164772 | Completed Phase 1 Results FDA Drug FDA Device

• 1 other identifier: LUD2014-012-VAC
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 5

Brief Summary

This is an open-label, multicenter, 2-arm study to evaluate the safety and preliminary efficacy of the addition of a vaccine therapy to 1 or 2 checkpoint inhibitors for NSCLC. Arm A: messenger ribonucleic acid (mRNA) Vaccine \[BI 1361849 (formerly CV9202)\] + anti-programmed death ligand 1 (PD-L1) antibody \[durvalumab\] Arm B: messenger ribonucleic acid (mRNA) Vaccine \[BI 1361849\] + anti-programmed death ligand 1 (PD-L1) \[durvalumab\] + anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody \[tremelimumab\] The run-in evaluation phase is followed by an expansion phase in which the cohort is expanded to 20 subjects (inclusive of subjects from the run-in).

Conditions

Metastatic Non-small Cell Lung Cancer; NSCLC

Keywords

mRNA Vaccine; durvalumab; MEDI4736; anti-PD-L1; tremelimumab; anti-CTLA-4; BI 1361849; PharmaJet Tropis® device

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)

  Adverse events (AEs) were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 20.0 and classified by MedDRA system organ class (SOC) and preferred term. The severity was assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. AEs were reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent was signed through 90 days after the last dose of study treatment. TEAEs are AEs that occurred or worsened in severity after administration of the first dose of study treatment. For each arm, the first 6 subjects were evaluated for dose limiting toxicities (DLTs). Deaths within the AE Reporting Period included all deaths that occurred during the study treatment period, or up to 90 days after the administration of the last dose of study drug or initiation of a new treatment.

  up to 15 months

Secondary Outcomes (11)

• Median PFS by RECIST 1.1 as Estimated Using the Kaplan-Meier Method

  up to 15 months

• Number of Subjects Without Progression at 8 and 24 Weeks by RECIST 1.1

  up to 24 weeks

• Median PFS by irRECIST as Estimated Using the Kaplan-Meier Method

  up to 15 months

• Number of Subjects Without Progression at 8 and 24 Weeks by irRECIST

  up to 24 weeks

• Number of Subjects With Best Overall Tumor Response By RECIST 1.1

  up to 15 months

Study Arms (2)

Arm A: BI 1361849 mRNA Vaccine + durvalumab

EXPERIMENTAL

The BI 1361849 mRNA vaccine comprises 6 drug product components (F2408 coding for MUC1, F2409 coding for survivin, F2410 coding for NY-ESO-1, F2624 coding for 5T4, F2625 coding for MAGE-C2, and F2626 coding for MAGE-C1), which were provided and administered separately; each component was administered twice, thus there were 12 intradermal administrations of 100 µL (80 µg) each for each dose. The PharmaJet Tropis® device was used for the administration of the BI 1361849 components. Durvalumab 1500 mg was to be administered as an intravenous (IV) infusion every 4 weeks for 12 cycles; BI 1361849 was to be administered as 14 doses over the 12 cycles.

Drug: Durvalumab; Biological: BI 1361849; Device: PharmaJet Tropis® device

Arm B: BI 1361849 mRNA Vaccine + durvalumab + tremelimumab

EXPERIMENTAL

The BI 1361849 mRNA vaccine comprises 6 drug product components (F2408 coding for MUC1, F2409 coding for survivin, F2410 coding for NY-ESO-1, F2624 coding for 5T4, F2625 coding for MAGE-C2, and F2626 coding for MAGE-C1), which were provided and administered separately; each component was administered twice, thus there were 12 intradermal administrations of 100 µL (80 µg) each for each dose. The PharmaJet Tropis® device was used for the administration of the BI 1361849 components. Durvalumab 1500 mg was to be administered as an intravenous (IV) infusion every 4 weeks for 12 cycles; tremelimumab 75 mg was to be administered as an intravenous (IV) infusion every 4 weeks for the first 4 cycles (Arm B only); BI 1361849 was to be administered as 14 doses over the 12 cycles.

Drug: Durvalumab; Drug: Tremelimumab; Biological: BI 1361849; Device: PharmaJet Tropis® device

Interventions

Durvalumab DRUG

anti-PD-L1

Also known as: MEDI4736

Arm A: BI 1361849 mRNA Vaccine + durvalumab; Arm B: BI 1361849 mRNA Vaccine + durvalumab + tremelimumab

Tremelimumab DRUG

anti-CTLA-4

Arm B: BI 1361849 mRNA Vaccine + durvalumab + tremelimumab

BI 1361849 BIOLOGICAL

mRNA Vaccine

Also known as: CV9202

Arm A: BI 1361849 mRNA Vaccine + durvalumab; Arm B: BI 1361849 mRNA Vaccine + durvalumab + tremelimumab

PharmaJet Tropis® device DEVICE

The PharmaJet Tropis® device was used for the intradermal administration of the BI 1361849 vaccine components.

Arm A: BI 1361849 mRNA Vaccine + durvalumab; Arm B: BI 1361849 mRNA Vaccine + durvalumab + tremelimumab

Eligibility Criteria

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

You may qualify if:

• Histologic confirmation of metastatic NSCLC. For subjects with known EGFR or ALK/ROS-1 mutations, prior therapy must have included an EGFR tyrosine kinase inhibitor or ALK/ROS-1 inhibitor, respectively. Subjects may have had 1 prior line of anti-PD-1/PD-L1 therapy. Subjects who received prior anti-PD-1/PD-L1 therapy must have progressed during or after the prior anti-PD-1/PD-L1 therapy treatment, but not prior to Week 12 of treatment.
• Measurable disease according to RECIST 1.1.
• Availability of archival (diagnostic) specimens or willing to undergo a pre-treatment biopsy.
• Subjects with treated brain metastases must have been treated with surgery and/or radiation therapy ≥ 21 days pre-study and must be clinically stable with no requirement for steroids.
• Laboratory parameters for vital functions should be in the normal range.
• ECOG Performance Status ≤ 2.
• Body weight \> 30 kg.

You may not qualify if:

• Subjects may not enter the study if they fulfill any of the following criteria:
• Treatment with an investigational agent within 4 weeks of starting treatment or prior treatment with anti-CTLA-4 therapy.
• Active, suspected or prior documented autoimmune disease, clinically significant cardiovascular disease, or clinically uncontrolled hypertension.
• History of pneumonitis or interstitial lung disease, or any unresolved immune-related adverse events following prior therapy.
• Major surgery within 4 weeks of starting treatment (or scheduled for surgery during the projected course of the study) or prior cancer vaccine treatment or allogeneic bone marrow transplantation.
• Subjects who are immunosuppressed, including those with known immunodeficiency or have active infection or other serious illnesses.
• Active infection including tuberculosis (TB), hepatitis B (HBV), hepatitis C, or human immunodeficiency virus (HIV). Subjects with a past or resolved HBV infection were eligible. Subjects positive for hepatitis C (HCV) antibody were eligible only if polymerase chain reaction was negative for HCV RNA.
• History of severe allergic reactions to any unknown allergens or components of the study drugs.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, bleeding disorders, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or serious chronic gastrointestinal conditions associated with diarrhea.
• Subjects must not have donated blood while on study and for at least 90 days following the last durvalumab treatment or for 6 months after the last dose of tremelimumab (whichever was longer).
• History of allogeneic organ transplant.
• History of leptomeningeal carcinomatosis.
• Active or prior malignancy except for history of other prior malignancy treated with curative intent which, in the opinion of the treating Investigator and the Sponsor, had minimal risk of interfering with safety or efficacy endpoints of the study.
• Women of childbearing potential who were pregnant as evidenced by positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) or nursing.
• Skin disease (e.g., psoriasis) that may prevent intradermal administration of the vaccine into the target areas.

Sponsors & Collaborators

• Ludwig Institute for Cancer Research: lead
• Cancer Research Institute, New York City: collaborator
• Boehringer Ingelheim: collaborator
• MedImmune LLC: collaborator
• CureVac: collaborator
• PharmaJet, Inc.: collaborator

Study Sites (5)

Research Facility

Gilbert, Arizona, 85234, United States

Location

Research Facility

Tampa, Florida, 33612, United States

Location

Research Facility

Detroit, Michigan, 48201, United States

Location

Research Facility

New York, New York, 10016, United States

Location

Research Facility

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 BACKGROUND

• Bohnsack O, Hoos A, Ludajic K. Adaptation of the immune related response criteria: irRECIST. Ann Oncol. 2014 Sep;25(suppl 4):iv361-iv72 [Abstract 4958]. doi: 10.1093/annonc/mdu342.23.

  BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

The study was not randomized. There was disparity between the arms regarding the number of subjects treated before and after the protocol amendment which enabled inclusion of subjects who had 1 prior line of anti-PD-1/PD-L1 therapy. Seven subjects were treated in Arm A and 1 subject in Arm B before implementation of the amendment. The results for Arms A and B are not intended for comparison. All post study follow-up for the collection of survival was discontinued as of 29 October 2021.

Results Point of Contact

• Title: Jonathan Skipper PhD
• Organization: Ludwig Institute for Cancer Research

jskipper@lcr.org

12124501539

Study Officials

• Jhanelle Gray, MD

  H. Lee Moffitt Cancer Center and Research Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2017
• First Posted: May 24, 2017
• Study Start: December 20, 2017
• Primary Completion: October 29, 2021
• Study Completion: October 29, 2021
• Last Updated: October 10, 2022
• Results First Posted: September 27, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)