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NCT03840902

M7824 With cCRT in Unresectable Stage III Non-small Cell Lung Cancer (NSCLC)

Terminated Phase 2 Results posted Last updated 16 January 2024
What this trial tests

Phase 2 trial testing M7824 in Non-small Cell Lung Cancer in 153 participants. Terminated before completion.

Timeline
16 April 2019
Primary endpoint
17 February 2023
17 February 2023

Quick facts

Lead sponsorEMD Serono Research & Development Institute, Inc.
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment153
Start date16 April 2019
Primary completion17 February 2023
Estimated completion17 February 2023
Sites104 locations across France, Japan, Netherlands, Belgium, Taiwan, Germany, South Korea, Argentina

Drugs / interventions tested

Conditions studied

Sponsor

EMD Serono Research & Development Institute, Inc. — full company profile →

Who can join

18 and older, any sex, with Non-small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator Primary · 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.

GroupValue95% CI
cCRT Plus M7824 Followed by M78243.71.9 – 5.6
cCRT Plus Placebo Followed by Durvalumab3.71.8 – 3.9
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events Secondary · 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

Participants with TEAEs
GroupValue95% CI
cCRT Plus M7824 Followed by M782470
cCRT Plus Placebo Followed by Durvalumab74
Participants with immunotherapy related TEAE
GroupValue95% CI
cCRT Plus M7824 Followed by M782448
cCRT Plus Placebo Followed by Durvalumab48
Participants with cisplatin/etoposide chemotherapy regimen related TEAE
GroupValue95% CI
cCRT Plus M7824 Followed by M78247
cCRT Plus Placebo Followed by Durvalumab11
Participants with carboplatin/paclitaxel chemotherapy regimen related TEAE
GroupValue95% CI
cCRT Plus M7824 Followed by M782446
cCRT Plus Placebo Followed by Durvalumab47
Participants with cisplatin/pemetrexed chemotherapy regimen related TEAE
GroupValue95% CI
cCRT Plus M7824 Followed by M782415
cCRT Plus Placebo Followed by Durvalumab11
Participants with radiotherapy related TEAE
GroupValue95% CI
cCRT Plus M7824 Followed by M782459
cCRT Plus Placebo Followed by Durvalumab60
Overall Survival (OS) Secondary · 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.

GroupValue95% CI
cCRT Plus M7824 Followed by M78244.60.1 – 22.3
cCRT Plus Placebo Followed by Durvalumab4.30.3 – 22.7
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator Secondary · 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.

GroupValue95% CI
cCRT Plus M7824 Followed by M782429.319.4 – 41.0
cCRT Plus Placebo Followed by Durvalumab32.121.9 – 43.6

Adverse events — posted to ClinicalTrials.gov

Time frame: Time from randomization up to data cut off (assessed up to 27 months). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

cCRT Plus M7824 Followed by M7824
Serious: 43/74 (58%)
Deaths: 13/75
cCRT Plus Placebo Followed by Durvalumab
Serious: 31/77 (40%)
Deaths: 5/78

Serious adverse events (83 terms)

ReactionSystemcCRT Plus M7824 Followed b…cCRT Plus Placebo Followed…
PneumonitisRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
PneumoniaInfections and infestations
NauseaGastrointestinal disorders
OesophagitisGastrointestinal disorders
SepsisInfections and infestations
Radiation oesophagitisInjury, poisoning and procedural complications
Radiation pneumonitisInjury, poisoning and procedural complications
PneumothoraxRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
Atrioventricular block completeCardiac disorders
PyrexiaGeneral disorders
Septic shockInfections and infestations
Urinary tract infectionInfections and infestations
DehydrationMetabolism and nutrition disorders
HaemoptysisRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
MyelosuppressionBlood and lymphatic system disorders
PancytopeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Cardiac arrestCardiac disorders
Myocardial infarctionCardiac disorders
Other adverse events (283 terms — click to expand)

ReactionSystemcCRT Plus M7824 Followed b…cCRT Plus Placebo Followed…
AnaemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
White blood cell count decreasedInvestigations
OesophagitisGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
Neutrophil count decreasedInvestigations
RashSkin and subcutaneous tissue disorders
PyrexiaGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
AstheniaGeneral disorders
Radiation oesophagitisInjury, poisoning and procedural complications
Lymphocyte count decreasedInvestigations
Platelet count decreasedInvestigations
EpistaxisRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
DiarrhoeaGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
Radiation skin injuryInjury, poisoning and procedural complications
HypoalbuminaemiaMetabolism and nutrition disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
DysphagiaGastrointestinal disorders
StomatitisGastrointestinal disorders
VomitingGastrointestinal disorders
Radiation pneumonitisInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations
HyponatraemiaMetabolism and nutrition disorders
InsomniaPsychiatric disorders
PneumoniaInfections and infestations
Lipase increasedInvestigations
Weight decreasedInvestigations
HyperthyroidismEndocrine disorders
Aspartate aminotransferase increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HaemoptysisRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Pneumonitis, Vomiting, Febrile neutropenia, Pneumonia, Nausea, Oesophagitis, Sepsis, Radiation oesophagitis.

Data from ClinicalTrials.gov NCT03840902 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting TGF-β signal transduction for fibrosis and cancer therapy.
    Peng D, Fu M, Wang M, Wei Y, et al · · 2022 · cited 752× · PMID 35461253 · DOI 10.1186/s12943-022-01569-x
  2. Novel therapies emerging in oncology to target the TGF-β pathway.
    Kim BG, Malek E, Choi SH, Ignatz-Hoover JJ, et al · · 2021 · cited 336× · PMID 33823905 · DOI 10.1186/s13045-021-01053-x
  3. Emerging new therapeutic antibody derivatives for cancer treatment.
    Jin S, Sun Y, Liang X, Gu X, et al · · 2022 · cited 304× · PMID 35132063 · DOI 10.1038/s41392-021-00868-x
  4. Targeting cytokine and chemokine signaling pathways for cancer therapy.
    Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
  5. Dual inhibition of TGF-β and PD-L1: a novel approach to cancer treatment.
    Gulley JL, Schlom J, Barcellos-Hoff MH, Wang XJ, et al · · 2022 · cited 132× · PMID 34854206 · DOI 10.1002/1878-0261.13146
  6. Blocking TGF-β Signaling To Enhance The Efficacy Of Immune Checkpoint Inhibitor.
    Bai X, Yi M, Jiao Y, Chu Q, et al · · 2019 · cited 115× · PMID 31807028 · DOI 10.2147/ott.s224013
  7. Biology drives the discovery of bispecific antibodies as innovative therapeutics.
    Nie S, Wang Z, Moscoso-Castro M, D'Souza P, et al · · 2020 · cited 79× · PMID 33928225 · DOI 10.1093/abt/tbaa003
  8. Determinants and Functions of CAFs Secretome During Cancer Progression and Therapy.
    Linares J, Marín-Jiménez JA, Badia-Ramentol J, Calon A. · · 2020 · cited 78× · PMID 33553157 · DOI 10.3389/fcell.2020.621070

Verify or expand the search:

Other trials of M7824

Trials testing the same drug.

Other recruiting trials for Non-small Cell Lung Cancer

Currently open trials in the same condition.

Other EMD Serono Research & Development Institute, Inc. trials

Trials by the same sponsor.

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