M7824 With cCRT in Unresectable Stage III Non-small Cell Lung Cancer (NSCLC)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03840902 |
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Recruitment Status :
Terminated
(Based on recommendations by an external Independent data Monitoring Committee (IDMC), Sponsor decided to discontinue this clinical study due to a low likelihood of achieving superiority in the efficacy endpoints versus standard of care.)
First Posted : February 15, 2019
Results First Posted : January 16, 2024
Last Update Posted : January 16, 2024
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Sponsor:
EMD Serono Research & Development Institute, Inc.
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )
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Brief Summary:
The main purpose of this study was to evaluate safety and efficacy in participants treated with concomitant chemoradiation therapy (cCRT) plus M7824 followed by M7824 compared to cCRT plus placebo followed by durvalumab.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Non-small Cell Lung Cancer | Drug: M7824 Drug: Placebo Drug: Durvalumab Drug: Etoposide Drug: Pemetrexed Drug: Carboplatin Drug: Paclitaxel Drug: Cisplatin Radiation: Intensity Modulated Radiation Therapy (IMRT) | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 153 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Multicenter, Double Blind, Randomized, Controlled Study of M7824 With Concurrent Chemoradiation Followed by M7824 Versus Concurrent Chemoradiation Plus Placebo Followed by Durvalumab in Participants With Unresectable Stage III Non-small Cell Lung Cancer |
| Actual Study Start Date : | April 16, 2019 |
| Actual Primary Completion Date : | February 17, 2023 |
| Actual Study Completion Date : | February 17, 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
MedlinePlus related topics:
Lung Cancer
Drug Information
available for:
Durvalumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: cCRT plus M7824 followed by M7824
Participants received cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with M7824 followed by M7824.
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Drug: M7824
Participants received intravenous infusion of 1200 milligram (mg) M7824 over 1 hour every 2 weeks (q2w) during cCRT and up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator. Drug: Etoposide Participants received etoposide 50 mg/m^2 intravenously over a minimum of 30 minutes up to 60 minutes daily on Day 1 to 5 and Day 29 to 33 during cCRT. Drug: Pemetrexed Participants received pemetrexed at a dose of 500 mg/m^2 intravenously over 10 minutes or according to local standards on Days 1, 22, and 43 during cCRT. Drug: Carboplatin Participants received carboplatin intravenously based on area under curve (AUC) 2 over 30 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT. Drug: Paclitaxel Participants received paclitaxel intravenously at a dose of 45 mg/m^2 over 60 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT. Drug: Cisplatin In combination with etoposide, participants received cisplatin 50 mg/m^2 intravenously over 60 minutes on Days 1, 8, 29, and 36 during cCRT. In combination with pemetrexed, participants received cisplatin 75 mg/m2 intravenously over 60 minutes on Days 1, 22, and 43 during cCRT. Radiation: Intensity Modulated Radiation Therapy (IMRT) Participants received IMRT 5 fractions per week for about 6 weeks (Total 60 gray [Gy]). |
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Active Comparator: cCRT plus placebo followed by durvalumab
Participants received cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with placebo matched to M7824 followed by durvalumab.
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Drug: Placebo
Participants received intravenous infusion of placebo matched to M7824 over 1 hour q2w during cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator. Drug: Durvalumab Participants received intravenous infusion of durvalumab 10 milligram per kilogram (mg/Kg) over 1 hour q2w up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator. Drug: Etoposide Participants received etoposide 50 mg/m^2 intravenously over a minimum of 30 minutes up to 60 minutes daily on Day 1 to 5 and Day 29 to 33 during cCRT. Drug: Pemetrexed Participants received pemetrexed at a dose of 500 mg/m^2 intravenously over 10 minutes or according to local standards on Days 1, 22, and 43 during cCRT. Drug: Carboplatin Participants received carboplatin intravenously based on area under curve (AUC) 2 over 30 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT. Drug: Paclitaxel Participants received paclitaxel intravenously at a dose of 45 mg/m^2 over 60 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT. Drug: Cisplatin In combination with etoposide, participants received cisplatin 50 mg/m^2 intravenously over 60 minutes on Days 1, 8, 29, and 36 during cCRT. In combination with pemetrexed, participants received cisplatin 75 mg/m2 intravenously over 60 minutes on Days 1, 22, and 43 during cCRT. Radiation: Intensity Modulated Radiation Therapy (IMRT) Participants received IMRT 5 fractions per week for about 6 weeks (Total 60 gray [Gy]). |
Primary Outcome Measures :
- Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator [ Time Frame: Time from randomization to the date of first documentation of PD or death, assessed approximately up to 27 months ]PFS was defined as the time from randomization to the date of first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was analyzed by using the Kaplan-Meier method.
Secondary Outcome Measures :
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events [ Time Frame: Time from randomization up to data cut off (assessed up to 27 months) ]Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily have a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious AEs and non-serious AEs. Treatment-related TEAEs: reasonably related to the study intervention.
- Overall Survival (OS) [ Time Frame: Time from randomization to the date of death due to any cause, assessed up to 27 months ]Overall Survival was defined as the time from randomization to the date of death due to any cause. The overall survival was analyzed by using the Kaplan-Meier method.
- Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator [ Time Frame: Time from randomization up to data cut off (assessed up to 27 months) ]ORR was defined as the percentage of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to RECIST v1.1as adjudicated by the Investigator. CR: Complete Response (CR) defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions.
- Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator [ Time Frame: Time from first documentation of objective response to the date of first documentation of PD or death due to any cause, assessed approximately up to 27 months ]DOR was defined as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was determined according to RECIST v1.1 and assessed by IRC. Results were calculated based on Kaplan-Meier estimates.
- Immediate Observed Serum Concentration at End of Infusion (Ceoi) of M7824 [ Time Frame: Pre-dose, 30 minutes after end of infusion on Day 1, 15, 29, 57, 85, 127, 157, 343 ]Ceoi is the serum concentration observed immediately at the end of infusion. This was taken directly from the observed M7824 concentration-time data.
- Serum Concentration Immediately Before Next Dosing (Ctrough) of M7824 [ Time Frame: Pre-dose, 30 minutes after end of infusion on Day 1, 15, 29, 57, 85, 127, 157, 343 ]Ctrough was the serum concentration observed immediately before next dosing.
- Number of Participants With Positive Antidrug Antibodies (ADA) [ Time Frame: Time from randomization up to data cut off (assessed up to 27 months) ]Serum samples were analyzed by a validated assay method to detect the presence of antidrug antibodies (ADA). Number of participants with positive ADA were reported.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Participants must have histologically documented NSCLC who present with Stage III locally advanced, unresectable disease (International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology
- Participants with tumor harboring an Epidermal growth factor receptor (EGFR) sensitizing (activating) mutation, Anaplastic lymphoma kinase (ALK) translocation, ROS-1 rearrangement are eligible.
- Participants must have adequate pulmonary function defined as a forced expiratory volume in 1 second (FEV1) greater than equals to (>=) 1.2 liters or >= 50% of predicted normal volume measured within 3 weeks prior to randomization.
- Adequate hematological, hepatic and renal function as defined in the protocol
- Contraceptive use by males or females will be consistent with local regulations on contraception methods for those participating in clinical studies
Exclusion Criteria:
- Participants with Mixed small cell with non-small cell lung cancer histology
- Recent major surgery within 4 weeks prior to entry into the study
- Significant acute or chronic infections including human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome, Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and active tuberculosis
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization
- Active autoimmune disease that has required systemic treatment in past 1 year (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs)
- Any prior systemic cytotoxic chemotherapy for their NSCLC or any antibody or drug targeting T-cell coregulatory proteins
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03840902
Locations
Show 104 study locations
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Investigators
| Study Director: | Medical Responsible | Merck KGaA, Darmstadt, Germany |
Study Documents (Full-Text)
Documents provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
Documents provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
Study Protocol [PDF] June 22, 2021
Statistical Analysis Plan [PDF] February 22, 2022
Additional Information:
| Responsible Party: | EMD Serono Research & Development Institute, Inc. |
| ClinicalTrials.gov Identifier: | NCT03840902 |
| Other Study ID Numbers: |
MS200647_0005 2018-003265-34 ( EudraCT Number ) |
| First Posted: | February 15, 2019 Key Record Dates |
| Results First Posted: | January 16, 2024 |
| Last Update Posted: | January 16, 2024 |
| Last Verified: | January 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21 |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union |
| Access Criteria: | Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal. |
| URL: | http://bit.ly/IPD21 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
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Non-small Cell Lung Cancer Bintrafusp alfa (proposed INN) M7824 |
Durvalumab Stage III INTR@PID LUNG 005 |
Additional relevant MeSH terms:
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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 Paclitaxel Etoposide Carboplatin Pemetrexed |
Durvalumab Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors Antineoplastic Agents, Immunological |