Metastatic Non-small Cell Lung CancerPhase 1/2NCT03164772
Phase 1/2 Study of Combination Immunotherapy and Messenger Ribonucleic Acid (mRNA) Vaccine in Subjects With NSCLC
A Phase 1/2 study testing Durvalumab, Tremelimumab and BI 1361849 in people with Metastatic Non-small Cell Lung Cancer and NSCLC, run by Ludwig Institute for Cancer Research at 5 sites in United States.
Trial 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]… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Non-small Cell Lung Cancer, NSCLC
- What is being tested?
- Durvalumab, Tremelimumab and BI 1361849
- Type of treatment
- Vaccines, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 5 sitesUnited States
- Study dates
- 20 Dec 2017to 29 Oct 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Research Facility
Detroit, Michigan, 48201
Research Facility
Gilbert, Arizona, 85234
Research Facility
Milwaukee, Wisconsin, 53226
Research Facility
New York, New York, 10016
Research Facility
Tampa, Florida, 33612
About this study
Official title: A Phase 1/2 Study of Combination Immunotherapy and mRNA Vaccine in Subjects With Non-small Cell Lung Cancer (NSCLC)
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).
Read the 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
- Being tested
- Durvalumab, Tremelimumab, BI 1361849, PharmaJet Tropis® device
- Keywords
- mRNA Vaccine, durvalumab, MEDI4736, anti-PD-L1, tremelimumab, anti-CTLA-4, BI 1361849, PharmaJet Tropis® device
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736
anti-PD-L1
TremelimumabDrug
anti-CTLA-4
BI 1361849Biological
Also called CV9202
mRNA Vaccine
PharmaJet Tropis® deviceDevice
The PharmaJet Tropis® device was used for the intradermal administration of the BI 1361849 vaccine components.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Durvalumab; Drug: Tremelimumab; Biological: BI 1361849; Device: PharmaJet Tropis® device |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 15 months
Secondary outcomes (11)
Median PFS by RECIST 1.1 as Estimated Using the Kaplan-Meier Method
Progression Free Survival (PFS) was measured from the date of the first dose of study treatment to the date of earliest disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or to the date of death, if disease progression did not occur. Per RECIST 1.1, progressive disease (PD) is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions or the presence of new lesions.
Measured: up to 15 months
Number of Subjects Without Progression at 8 and 24 Weeks by RECIST 1.1
Progression-free Survival (PFS) was measured from the date of the first dose of study treatment to the date of earliest disease progression or to the date of death, if disease progression did not occur. Per RECIST 1.1, progressive disease (PD) is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions or the presence of new lesions.
Measured: up to 24 weeks
Median PFS by irRECIST as Estimated Using the Kaplan-Meier Method
Progression-free Survival (PFS) was measured from the date of the first dose of study treatment to the date of earliest disease progression according to immune related Response Evaluation Criteria in Solid Tumors (irRECIST) or to the date of death, if disease progression did not occur. Per irRECIST, progressive disease (irPD) is defined as a ≥ 20% increase from nadir in the total measurable tumor burden (TMTB).
Measured: up to 15 months
Number of Subjects Without Progression at 8 and 24 Weeks by irRECIST
Progression-free Survival (PFS) was measured from the date of the first dose of study treatment to the date of earliest disease progression or to the date of death, if disease progression did not occur. Per irRECIST, progressive disease (irPD) is defined as a ≥ 20% increase from nadir in the total measurable tumor burden (TMTB).
Measured: up to 24 weeks
Number of Subjects With Best Overall Tumor Response By RECIST 1.1
Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5, 7, 9, and 11 during study treatment, and during on-study follow-up every 8 weeks starting 8 weeks after the last disease assessment. Per RECIST 1.1, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions; partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; PD: ≥ 20% increase in the sum of the longest diameter of target lesions or the presence of new lesions; stable disease (SD): small changes that do not meet above criteria.
Measured: up to 15 months
Number of Subjects With Objective Responses at 8 and 24 Weeks By RECIST 1.1
Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5, 7, 9, and 11 during study treatment, and during on-study follow-up every 8 weeks starting 8 weeks after the last disease assessment. Per RECIST 1.1, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions; partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; PD: ≥ 20% increase in the sum of the longest diameter of target lesions or presence of new lesions; stable disease (SD): small changes that do not meet above criteria. An Objective Response is defined as a CR or PR over a period of at least 4 weeks.
Measured: up to 24 weeks
Duration of Response (DoR) By RECIST 1.1
Duration of Response (DoR) was defined as the interval between the date of earliest determination of CR or PR to the date of earliest determination of progressive disease (PD), clinical progression or death, whatever occurred first.
Measured: up to 15 months
Number of Subjects With Best Overall Tumor Response By irRECIST
Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5, 7, 9, and 11 during study treatment, and during on-study follow-up every 8 weeks starting 8 weeks after the last disease assessment. Per irRECIST, responses are categorized as follows: Complete Response (irCR): Complete disappearance of all target lesions; Partial Response (irPR): ≥ 30% decrease from baseline in the total measurable tumor burden (TMTB); Progressive Disease (irPD): ≥ 20% increase from nadir in TMTB; Stable Disease (irSD): not meeting above criteria.
Measured: up to 15 months
Number of Subjects With Objective Responses at 8 and 24 Weeks By irRECIST
Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5, 7, 9, and 11 during study treatment, and during on-study follow-up every 8 weeks starting 8 weeks after the last disease assessment. Per irRECIST, responses are categorized as follows: irCR: Complete disappearance of all target lesions; irPR: ≥ 30% decrease from baseline in the total measurable tumor burden (TMTB); irPD: ≥ 20% increase from nadir in TMTB; irSD: not meeting above criteria.
An Objective Response is defined as an irCR or irPR over a period of at least 4 weeks.
Measured: up to 24 weeks
Duration of Response (DoR) by irRECIST
Duration of Response (DoR) was defined as the interval between the date of earliest determination of irCR or irPR to the date of earliest determination of progressive disease (irPD), clinical progression or death, whatever occurred first.
Measured: Up tp 15 months
Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method
After completion of treatment, all subjects were followed for survival every 6 months following initiation of study treatment until October 29, 2021 when all post-study follow-up was completed. OS was measured from the date of the first dose of study treatment to the date of death or last follow-up. Subjects lost to follow-up were censored on the date when they were last known to be alive.
Measured: up to October 29, 2021
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2017
- Study start20 Dec 2017
- Primary completion29 Oct 2021
- Study completion29 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Metastatic Non-small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig Institute for Cancer Research
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research Institute, New York City, Boehringer Ingelheim, MedImmune LLC, CureVac, PharmaJet, Inc.
- Responsible party
- Sponsor
- Investigators
- Jhanelle Gray, MD, Study chair, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03164772
- Sponsor's protocol ID
- LUD2014-012-VAC
- Status last verified
- Oct 2022
- First submitted
- 22 May 2017
- Last updated
- 10 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 19097774Bohnsack 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.
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of Combination Immunotherapy and mRNA Vaccine in Subjects With Non-small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT03164772
- Acronym / sponsor ID
- LUD2014-012-VAC
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Ludwig Institute for Cancer ResearchUniversity, hospital or other
- Collaborators
- Cancer Research Institute, New York City, Boehringer Ingelheim, MedImmune LLC, CureVac, PharmaJet, Inc.
- Study start
- 20 Dec 2017 (actual)
- Primary completion
- 29 Oct 2021 (actual)
- Study completion
- 29 Oct 2021 (actual)
- First posted
- 24 May 2017 (actual)
- Results
- Posted 27 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: BI 1361849 mRNA Vaccine + durvalumab | Experimental | Drug: Durvalumab, Biological: BI 1361849, Device: PharmaJet Tropis® deviceThe 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. |
| Arm B: BI 1361849 mRNA Vaccine + durvalumab + tremelimumab | Experimental | Drug: Durvalumab, Drug: Tremelimumab, Biological: BI 1361849, Device: PharmaJet Tropis® deviceThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DurvalumabAlso: MEDI4736anti-PD-L1 | Drug | Arm A: BI 1361849 mRNA Vaccine + durvalumab, Arm B: BI 1361849 mRNA Vaccine + durvalumab + tremelimumab |
| Tremelimumabanti-CTLA-4 | Drug | Arm B: BI 1361849 mRNA Vaccine + durvalumab + tremelimumab |
| BI 1361849Also: CV9202mRNA Vaccine | Biological | Arm A: BI 1361849 mRNA Vaccine + durvalumab, Arm B: BI 1361849 mRNA Vaccine + durvalumab + tremelimumab |
| PharmaJet Tropis® deviceThe PharmaJet Tropis® device was used for the intradermal administration of the BI 1361849 vaccine components. | Device | Arm A: BI 1361849 mRNA Vaccine + durvalumab, Arm B: BI 1361849 mRNA Vaccine + durvalumab + tremelimumab |
Primary outcome
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
Time frame: up to 15 months
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.
11 secondary outcomes
Median PFS by RECIST 1.1 as Estimated Using the Kaplan-Meier Method
Time frame: up to 15 months
Number of Subjects Without Progression at 8 and 24 Weeks by RECIST 1.1
Time frame: up to 24 weeks
Median PFS by irRECIST as Estimated Using the Kaplan-Meier Method
Time frame: up to 15 months
Number of Subjects Without Progression at 8 and 24 Weeks by irRECIST
Time frame: up to 24 weeks
Number of Subjects With Best Overall Tumor Response By RECIST 1.1
Time frame: up to 15 months
Number of Subjects With Objective Responses at 8 and 24 Weeks By RECIST 1.1
Time frame: up to 24 weeks
Duration of Response (DoR) By RECIST 1.1
Time frame: up to 15 months
Number of Subjects With Best Overall Tumor Response By irRECIST
Time frame: up to 15 months
Number of Subjects With Objective Responses at 8 and 24 Weeks By irRECIST
Time frame: up to 24 weeks
Duration of Response (DoR) by irRECIST
Time frame: Up tp 15 months
Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method
Time frame: up to October 29, 2021
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19097774Eisenhauer 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.
- BackgroundBohnsack 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.
- Individual participant dataSharing planned: No
Related trials for Metastatic Non-small Cell Lung Cancer
RecruitingPhase 1/2
Study of RAS(ON) Inhibitors in Combination With Ivonescimab in Patients With Solid Tumors
Advanced Solid Tumors, Metastatic Solid Tumors
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
RecruitingPhase 3
A Study to Learn More About How Well Sevabertinib Works and How Safe it is Compared With Standard Treatment, in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)
Advanced Non-small Cell Lung Cancer, HER2 Mutation
RecruitingPhase 3
Osimertinib With or Without Bevacizumab as Initial Treatment for Patients With EGFR-Mutant Lung Cancer
Advanced Lung Non-Squamous Non-Small Cell Carcinoma, Metastatic Lung Non-Squamous Non-Small Cell Carcinoma
Active, not recruitingPhase 3
A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure
Carcinoma, Non-Small-Cell Lung
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jhanelle Gray, MD study chair
H. Lee Moffitt Cancer Center and Research Institute
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Durvalumab, Tremelimumab and BI 1361849 in people with Metastatic Non-small Cell Lung Cancer and NSCLC, run by Ludwig Institute for Cancer Research at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) (time frame: up to 15 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03164772, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2022.