Clinical Trials /

Phase 1/2 Study of Combination Immunotherapy and mRNA Vaccine in Subjects With NSCLC

NCT03164772

Description:

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: mRNA Vaccine [BI 1361849 (formerly CV9202)] + anti-PD-L1 [durvalumab] Arm B: mRNA Vaccine [BI 1361849] + anti-PD-L1 [durvalumab] + anti-CTLA-4 [tremelimumab] For each arm of the study, there is a dose evaluation phase in which the Recommended Combination Dose (RCD) is determined according to a standard 3 + 3 design. The dose evaluation phase is followed by an expansion phase, in which the cohort at the RCD is expanded to 20 subjects (inclusive of the subjects from the dose evaluation cohort).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 1/2 Study of Combination Immunotherapy and mRNA Vaccine in Subjects With NSCLC
  • Official Title: A Phase 1/2 Study of Combination Immunotherapy and mRNA Vaccine in Subjects With Non-small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: LUD2014-012-VAC
  • NCT ID: NCT03164772

Conditions

  • Metastatic Non-small Cell Lung Cancer
  • NSCLC

Interventions

DrugSynonymsArms
DurvalumabMEDI4736Arm A
TremelimumabArm B
BI 1361849CV9202Arm A

Purpose

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: mRNA Vaccine [BI 1361849 (formerly CV9202)] + anti-PD-L1 [durvalumab] Arm B: mRNA Vaccine [BI 1361849] + anti-PD-L1 [durvalumab] + anti-CTLA-4 [tremelimumab] For each arm of the study, there is a dose escalation phase in which the Recommended Combination Dose (RCD) is determined according to a standard 3 + 3 design. The dose escalation phase is followed by an expansion phase, in which the cohort at the RCD is expanded to 20 subjects (inclusive of the subjects from the dose escalation cohort).

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimentalThere is a dose escalation phase in which the Recommended Combination Dose is determined according to a standard 3 + 3 design. The dose escalation phase is followed by an expansion phase, in which the cohort at the Recommended Combination Dose is expanded to 20 subjects (inclusive of the subjects from the dose escalation cohort).
  • Durvalumab
Arm BExperimentalThe dose escalation phase is followed by an expansion phase, in which the cohort at the Recommended Combination Dose is expanded to 20 subjects (inclusive of the subjects from the dose escalation cohort). For Arm B, there will be an additional Control group (n = 10) added to the expansion phase in which the subjects will receive only durvalumab every 4 weeks.
  • Durvalumab
  • Tremelimumab

Eligibility Criteria

        Inclusion Criteria

          1. Histologic confirmation of metastatic NSCLC. For subjects with EGFR mutations, prior
             therapy must have included an EGFR tyrosine kinase inhibitor. Subjects must not have
             ALK rearrangement.

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

          3. 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.

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

          5. ECOG Performance Status ≤ 2.

        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 a checkpoint inhibitor (CTLA-4, PD-1 or PD-L1 antibodies).

          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 including tuberculosis or other serious illnesses.

          6. Skin disease (e.g., psoriasis) that may prevent intradermal administration of the
             vaccine into the target areas.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Adverse Events
Time Frame:up to 15 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:up to 24 weeks
Safety Issue:
Description:Objective Response Rate at 8 and 24 Weeks
Measure:Progression Free Survival (PFS)
Time Frame:24 weeks
Safety Issue:
Description:Progression Free Survival (PFS) at 8 and 24 weeks
Measure:Duration of Response (DoR)
Time Frame:up to 15 months
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:up to 5 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Ludwig Institute for Cancer Research

Trial Keywords

  • mRNA Vaccine
  • Durvalumab
  • MEDI4736
  • anti-PD-L1
  • tremelimumab
  • anti-CTLA-4
  • BI 1361849

Last Updated

May 22, 2017