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

• ClinicalTrials.gov Identifier: NCT03164772
• Recruitment Status: Active, not recruiting
• First Posted: May 24, 2017
• Last Update Posted: February 23, 2021
• Sponsor: Ludwig Institute for Cancer Research
• Collaborators: Cancer Research Institute, New York City; Boehringer Ingelheim; MedImmune LLC; CureVac AG; PharmaJet, Inc.
• Information provided by (Responsible Party): Ludwig Institute for Cancer Research

Study Description

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: mRNA Vaccine [BI 1361849 (formerly CV9202)] + anti-PD-L1 [durvalumab] Arm B: mRNA Vaccine [BI 1361849] + anti-PD-L1 [durvalumab] + anti-CTLA-4 [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).

Condition or disease	Intervention/treatment	Phase
Metastatic Non-small Cell Lung Cancer; NSCLC	Drug: Durvalumab; Drug: Tremelimumab; Biological: BI 1361849	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 56 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Study of Combination Immunotherapy and mRNA Vaccine in Subjects With Non-small Cell Lung Cancer (NSCLC)
• Actual Study Start Date: December 20, 2017
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A; The run-in dose evaluation phase is followed by an expansion phase in which the cohort is expanded to 20 subjects (including subjects from the run-in).	Drug: Durvalumab; anti-PD-L1; Other Name: MEDI4736; Biological: BI 1361849; mRNA Vaccine; Other Name: CV9202
Experimental: Arm B; The run-in dose evaluation phase is followed by an expansion phase in which the cohort is expanded to 20 subjects (including subjects from the run-in).	Drug: Durvalumab; anti-PD-L1; Other Name: MEDI4736; Drug: Tremelimumab; anti-CTLA-4; Biological: BI 1361849; mRNA Vaccine; Other Name: CV9202

Outcome Measures

Primary Outcome Measures :

1. Number of Adverse Events [ Time Frame: up to 15 months ]

Secondary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: up to 24 weeks ]
   Objective Response Rate at 8 and 24 Weeks
2. Progression Free Survival (PFS) [ Time Frame: 24 weeks ]
   Progression Free Survival (PFS) at 8 and 24 weeks
3. Duration of Response (DoR) [ Time Frame: up to 15 months ]
4. Overall Survival (OS) [ Time Frame: up to 5 years ]

Eligibility Criteria

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

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 treatment, but not prior to Week 12 of treatment.
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 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 including tuberculosis or other serious illnesses.
6. Skin disease (e.g., psoriasis) that may prevent intradermal administration of the vaccine into the target areas.

Contacts and Locations

Locations

United States, Arizona

Research Facility

Gilbert, Arizona, United States, 85234

United States, Florida

Research Facility

Tampa, Florida, United States, 33612

United States, Michigan

Research Facility

Detroit, Michigan, United States, 48201

United States, New York

Research Facility

New York, New York, United States, 10016

United States, Wisconsin

Research Facility

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Ludwig Institute for Cancer Research

Cancer Research Institute, New York City

Boehringer Ingelheim

MedImmune LLC

CureVac AG

PharmaJet, Inc.

Investigators

• Study Chair: Jhanelle Gray, MD; H. Lee Moffitt Cancer Center and Research Institute

More Information

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT03164772
• Other Study ID Numbers: LUD2014-012-VAC
• First Posted: May 24, 2017
• Last Update Posted: February 23, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Ludwig Institute for Cancer Research:

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

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Durvalumab; Tremelimumab; Antineoplastic Agents, Immunological; Antineoplastic Agents