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

NCT ID: NCT03164772

Last Updated: 2022-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-20
• Study Completion Date: 2021-10-29

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).

Detailed Description

This was a Phase 1/2, 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 in subjects with NSCLC.

Up to 56 subjects were planned for enrollment from up to 8 clinical sites in 2 arms:

Arm A: mRNA Vaccine [BI 1361849 (formerly CV9202)] + anti-PD-L1 antibody [durvalumab]

Arm B: mRNA Vaccine [BI 1361849] + anti-PD-L1 [durvalumab] + anti-CTLA-4 antibody [tremelimumab]

Subjects must have had histologically confirmed 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 and must not have had progression at or before 12 weeks after start of the prior anti-PD-1/PD-L1 treatment.

Conditions

Metastatic Non-small Cell Lung Cancer; NSCLC

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: BI 1361849 mRNA Vaccine + durvalumab

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.

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: DRUG

anti-PD-L1

BI 1361849

Intervention Type: BIOLOGICAL

mRNA Vaccine

PharmaJet Tropis® device

Intervention Type: DEVICE

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

Arm B: BI 1361849 mRNA Vaccine + durvalumab + tremelimumab

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.

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: DRUG

anti-PD-L1

Tremelimumab

Intervention Type: DRUG

anti-CTLA-4

BI 1361849

Intervention Type: BIOLOGICAL

mRNA Vaccine

PharmaJet Tropis® device

Intervention Type: DEVICE

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

Interventions

Durvalumab

anti-PD-L1

Intervention Type: DRUG

Tremelimumab

anti-CTLA-4

Intervention Type: DRUG

BI 1361849

mRNA Vaccine

Intervention Type: BIOLOGICAL

PharmaJet Tropis® device

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

Intervention Type: DEVICE

Other Intervention Names

MEDI4736; CV9202

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Measurable disease according to RECIST 1.1.

3. Availability of archival (diagnostic) specimens or willing to undergo a pre-treatment biopsy.

4. 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.

5. Laboratory parameters for vital functions should be in the normal range.

6. ECOG Performance Status ≤ 2.

7. Body weight > 30 kg.

Exclusion Criteria

Subjects may not enter the study if they fulfill any of the following criteria:

1. Treatment with an investigational agent within 4 weeks of starting treatment or prior treatment with anti-CTLA-4 therapy.

2. Active, suspected or prior documented autoimmune disease, clinically significant cardiovascular disease, or clinically uncontrolled hypertension.

3. History of pneumonitis or interstitial lung disease, or any unresolved immune-related adverse events following prior therapy.

4. 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.

5. Subjects who are immunosuppressed, including those with known immunodeficiency or have active infection or other serious illnesses.

6. 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.

7. History of severe allergic reactions to any unknown allergens or components of the study drugs.

8. 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.

9. 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).

10. History of allogeneic organ transplant.

11. History of leptomeningeal carcinomatosis.

12. 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.

13. 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.

14. Skin disease (e.g., psoriasis) that may prevent intradermal administration of the vaccine into the target areas.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Research Institute, New York City

OTHER

Sponsor Role: collaborator

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

MedImmune LLC

INDUSTRY

Sponsor Role: collaborator

CureVac

INDUSTRY

Sponsor Role: collaborator

PharmaJet, Inc.

INDUSTRY

Sponsor Role: collaborator

Ludwig Institute for Cancer Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jhanelle Gray, MD

Role: STUDY_CHAIR

H. Lee Moffitt Cancer Center and Research Institute

Locations

Research Facility

Gilbert, Arizona, United States

Research Facility

Tampa, Florida, United States

Research Facility

Detroit, Michigan, United States

Research Facility

New York, New York, United States

Research Facility

Milwaukee, Wisconsin, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 19097774 (View on PubMed)

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.

Reference Type: BACKGROUND

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

LUD2014-012-VAC

Identifier Type: -

Identifier Source: org_study_id