NCT02517398

MSB0011359C (M7824) in Metastatic or Locally Advanced Solid Tumors

Completed Phase 1 Results posted Last updated 3 May 2024

What this trial tests

Phase 1 trial testing MSB0011359C in Solid Tumors in 600 participants. Completed in 23 May 2022.

Timeline

31 August 2015

Primary endpoint
23 May 2022

23 May 2022

Quick facts

Lead sponsor	EMD Serono Research & Development Institute, Inc.
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	600
Start date	31 August 2015
Primary completion	23 May 2022
Estimated completion	23 May 2022
Sites	118 locations across France, Italy, Japan, Belgium, Taiwan, United Kingdom, Germany, South Korea

Drugs / interventions tested

• MSB0011359C — full drug profile →

Conditions studied

• Solid Tumors — all drugs for Solid Tumors →

Sponsor

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

Who can join

18 and older, any sex, with Solid Tumors. 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.

Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Primary · From start of study drug administration up to 139 weeks

Adverse event (AE): any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening

Participants with TEAEs

Group	Value	95% CI
Dose-escalation: M7824 0.3 - 10 mg/kg	3
Dose-escalation: M7824 1 mg/kg	3
Dose-escalation: M7824 1 - 1200 mg	4
Dose-escalation: M7824 3 mg/kg	3
Dose-escalation: M7824 10 mg/kg	6
Dose-escalation: M7824 20 mg/kg	10
Dose-escalation: M7824 30 mg/kg	7
Dose-escalation: M7824 2400 mg/Infusion	3
Dose-escalation: HCC-3 mg/kg	6

Participants with Serious TEAEs

Group	Value	95% CI
Dose-escalation: M7824 0.3 - 10 mg/kg	2
Dose-escalation: M7824 1 mg/kg	2
Dose-escalation: M7824 1 - 1200 mg	2
Dose-escalation: M7824 3 mg/kg	1
Dose-escalation: M7824 10 mg/kg	1
Dose-escalation: M7824 20 mg/kg	8
Dose-escalation: M7824 30 mg/kg	3
Dose-escalation: M7824 2400 mg/Infusion	2
Dose-escalation: HCC-3 mg/kg	1

Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death Primary · From start of study drug administration up to 139 weeks

Treatment-related TEAEs are any untoward medical occurrence in a participant who received study drug with causal relationship with the investigational product as assessed by the investigator. Related TEAEs were events with relationship missing, unknown or yes. Number of participants With treatment-related TEAEs, treatment-related serious TEAEs and treatment-related TEAE leading to death were reported.

Treatment-related TEAEs

Group	Value	95% CI
Dose-escalation: M7824 0.3 - 10 mg/kg	2
Dose-escalation: M7824 1 mg/kg	0
Dose-escalation: M7824 1 - 1200 mg	2
Dose-escalation: M7824 3 mg/kg	2
Dose-escalation: M7824 10 mg/kg	5
Dose-escalation: M7824 20 mg/kg	6
Dose-escalation: M7824 30 mg/kg	7
Dose-escalation: M7824 2400 mg/Infusion	2
Dose-escalation: HCC-3 mg/kg	4

Treatment-related serious TEAEs

Group	Value	95% CI
Dose-escalation: M7824 0.3 - 10 mg/kg	0
Dose-escalation: M7824 1 mg/kg	0
Dose-escalation: M7824 1 - 1200 mg	0
Dose-escalation: M7824 3 mg/kg	1
Dose-escalation: M7824 10 mg/kg	1
Dose-escalation: M7824 20 mg/kg	3
Dose-escalation: M7824 30 mg/kg	1
Dose-escalation: M7824 2400 mg/Infusion	1
Dose-escalation: HCC-3 mg/kg	0

Treatment-related TEAE leading to death

Group	Value	95% CI
Dose-escalation: M7824 0.3 - 10 mg/kg	0
Dose-escalation: M7824 1 mg/kg	0
Dose-escalation: M7824 1 - 1200 mg	0
Dose-escalation: M7824 3 mg/kg	0
Dose-escalation: M7824 10 mg/kg	0
Dose-escalation: M7824 20 mg/kg	0
Dose-escalation: M7824 30 mg/kg	0
Dose-escalation: M7824 2400 mg/Infusion	0
Dose-escalation: HCC-3 mg/kg	0

Number of Participants With TEAEs and Related TEAEs Based on Severity According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03 Primary · From start of study drug administration up to 139 weeks

AEs were graded according to severity using NCI-CTCAE Version 4.03. Severity of TEAEs were graded as Grade 1: mild (not causing any significant problem, dose adjustment not required), Grade 2: moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event), Grade 3: Severe (caused problem that interferes significantly with usual activities or the clinical status, study drug stopped due to adverse event), Grade 4: Life-threatening, Grade 5: Death. Number of Participants with TEAEs and Related TEAEs Based o

Grade >= 3 TEAE

Group	Value	95% CI
Dose-escalation: M7824 0.3 - 10 mg/kg	3
Dose-escalation: M7824 1 mg/kg	3
Dose-escalation: M7824 1 - 1200 mg	2
Dose-escalation: M7824 3 mg/kg	1
Dose-escalation: M7824 10 mg/kg	4
Dose-escalation: M7824 20 mg/kg	7
Dose-escalation: M7824 30 mg/kg	5
Dose-escalation: M7824 2400 mg/Infusion	2
Dose-escalation: HCC-3 mg/kg	6

Grade >= 4 TEAE

Group	Value	95% CI
Dose-escalation: M7824 0.3 - 10 mg/kg	0
Dose-escalation: M7824 1 mg/kg	0
Dose-escalation: M7824 1 - 1200 mg	2
Dose-escalation: M7824 3 mg/kg	0
Dose-escalation: M7824 10 mg/kg	1
Dose-escalation: M7824 20 mg/kg	2
Dose-escalation: M7824 30 mg/kg	0
Dose-escalation: M7824 2400 mg/Infusion	0
Dose-escalation: HCC-3 mg/kg	1

Treatment-related Grade >= 3 TEAE

Group	Value	95% CI
Dose-escalation: M7824 0.3 - 10 mg/kg	0
Dose-escalation: M7824 1 mg/kg	0
Dose-escalation: M7824 1 - 1200 mg	0
Dose-escalation: M7824 3 mg/kg	1
Dose-escalation: M7824 10 mg/kg	2
Dose-escalation: M7824 20 mg/kg	4
Dose-escalation: M7824 30 mg/kg	2
Dose-escalation: M7824 2400 mg/Infusion	0
Dose-escalation: HCC-3 mg/kg	0

Treatment-related Grade >= 4 TEAE

Group	Value	95% CI
Dose-escalation: M7824 0.3 - 10 mg/kg	0
Dose-escalation: M7824 1 mg/kg	0
Dose-escalation: M7824 1 - 1200 mg	0
Dose-escalation: M7824 3 mg/kg	0
Dose-escalation: M7824 10 mg/kg	1
Dose-escalation: M7824 20 mg/kg	0
Dose-escalation: M7824 30 mg/kg	0
Dose-escalation: M7824 2400 mg/Infusion	0
Dose-escalation: HCC-3 mg/kg	0

Dose-escalation: Number of Participants With Dose-Limiting Toxicities According to the National Cancer Institute Common Terminology Criteria For Adverse Events(NCI-CTCAE), v4.03 Primary · From start of study drug administration up to 21 days

A DLT was defined as any grade \>= 3 Adverse Event (AE) suspected to be related to IMP by the Investigator and / or Sponsor occurring in the DLT evaluation period confirmed by the Safety Monitoring Committee (SMC) to be relevant for the IMP treatment. According to the NCI-CTCAE, v4.03, occurring in the DLT evaluation period and assessed to be related to study treatment by the Investigator and / or Sponsor confirmed by the safety monitoring committee to be relevant for the study treatment.

Group	Value	95% CI
Dose-escalation: M7824 1 mg/kg	0
Dose-escalation: M7824 3 mg/kg	0
Dose-escalation: M7824 10 mg/kg	0
Dose-escalation: M7824 20 mg/kg	1
Dose-escalation: M7824 30 mg/kg	0
Dose-escalation: M7824 2400 mg/Infusion	0

Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) Primary · From date of randomization up to Week 66

BOR according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and as adjudicated by the Independent Endpoint Review Committee (IRC). BOR is defined as sum of complete response and partial response (CR+PR). For target lesions (TLs), CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the sum of largest diameter (SLD) of the TLs, taking as a reference the baseline SLD.

Complete response (CR)

Group	Value	95% CI
Dose-expansion: HCC Ascending Dose 1200mg	0
Dose-expansion: HCC-2L	0
Dose-expansion: Melanoma PD-L1 Fail	0
Dose-expansion: NSCLC PD-L1 Fail	0
Dose-expansion: Pancreatic Adenocarcinoma	0
Dose-expansion: Esophageal Adenocarcinoma	0
Dose-expansion: Colorectal Carcinoma	0
Dose-expansion: Triple Negative Breast Cancer	1
Dose-expansion: Glioblastoma	0
Dose-expansion: Squamous Cell Carcinoma of Head and Neck	0
Dose-expansion: Cervical Cancer	0
Dose-expansion: NSCLC-2L 1200 mg	0

Partial response (PR)

Group	Value	95% CI
Dose-expansion: HCC Ascending Dose 1200mg	4
Dose-expansion: HCC-2L	6
Dose-expansion: Melanoma PD-L1 Fail	2
Dose-expansion: NSCLC PD-L1 Fail	3
Dose-expansion: Pancreatic Adenocarcinoma	1
Dose-expansion: Esophageal Adenocarcinoma	6
Dose-expansion: Colorectal Carcinoma	1
Dose-expansion: Triple Negative Breast Cancer	2
Dose-expansion: Glioblastoma	2
Dose-expansion: Squamous Cell Carcinoma of Head and Neck	4
Dose-expansion: Cervical Cancer	2
Dose-expansion: NSCLC-2L 1200 mg	7

Dose-expansion: Disease Control Rate According to Response Assessment in Neuro-Oncology (RANO) as Adjudicated by the IRC for Participants With Glioblastoma Primary · From date of randomization up to Week 66

DCR is defined as the percentage of participants with a confirmed CR+PR+SD+ Non-CR/non-PD at any time as per RANO criteria. A responder is a participant with a Complete Response (CR) or Partial Response (PR), and a non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD) assessed by the RANO criteria. CR is no T1 gadolinium enhancing disease, no new lesions, or corticosteroids, and stable or decreasing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR). PR is ≥50% decrease in T1 gadolinium enhancing disease, no new lesions, stable or decreasing T2/FLAIR or co

Group	Value	95% CI
Dose-expansion: Glioblastoma	22.9	10.4 – 40.1

Maximum Concentration (Cmax) of M7824 in Plasma Secondary · 0 hours (pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose

Cmax was obtained directly from the concentration versus time curve.

Group	Value	95% CI
Dose-escalation: M7824 0.3 mg/kg	7.08	± 9.1
Dose-escalation: M7824 1 mg/kg	22.5	± 44.2
Dose-escalation: M7824 3 mg/kg	92.8	± 74.8
Dose-escalation: M7824 10 mg/kg	233	± 9.1
Dose-escalation: M7824 20 mg/kg	503	± 15.7
Dose-escalation: M7824 30 mg/kg	766	± 8.0
Dose-escalation: M7824 2400 mg/Infusion	943	± 19.7
Dose-expansion: All Solid Tumors 1200mg	411	± 28.5
Dose-expansion: NSCLC-2L 500 mg	185	± 39.7

Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824 Secondary · 0 hours (pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose post-dose

Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (336 hours).

Group	Value	95% CI
Dose-escalation: M7824 0.3 mg/kg	747	± 25.0
Dose-escalation: M7824 1 mg/kg	3170	± 38.6
Dose-escalation: M7824 3 mg/kg	11000	± 33.6
Dose-escalation: M7824 10 mg/kg	32600	± 10.1
Dose-escalation: M7824 20 mg/kg	62200	± 31.2
Dose-escalation: M7824 30 mg/kg	114000	± 9.1
Dose-escalation: M7824 2400 mg/Infusion	144000	± 14.3
Dose-expansion: All Solid Tumors 1200mg	60300	± 27.6
Dose-expansion: NSCLC-2L 500 mg	24900	± 33.7

Apparent Terminal Half Life (t1/2) of M7824 Secondary · Pre-dose, 0, 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose

Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life is calculated by dividing the natural logarithm to the base e (Log e) multiplied by (\*) 2/ λz, where 'λz' is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

Group	Value	95% CI
Dose-escalation: M7824 0.3 mg/kg	74.0	± 20.9
Dose-escalation: M7824 1 mg/kg	120	± 16.9
Dose-escalation: M7824 3 mg/kg	125	± 22.6
Dose-escalation: M7824 10 mg/kg	160	± 23.0
Dose-escalation: M7824 20 mg/kg	172	± 30.3
Dose-escalation: M7824 30 mg/kg	171	± 31.5
Dose-escalation: M7824 2400 mg/Infusion	177	± 15.8
Dose-expansion: All Solid Tumors 1200mg	152	± 23.3
Dose-expansion: NSCLC-2L 500 mg	145	± 23.5

Trough Plasma Concentration (Ctrough) of M7824 Secondary · 0 hours (Pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose

Ctrough is the plasma concentration of a drug prior to administration.

Group	Value	95% CI
Dose-escalation: M7824 0.3 mg/kg	NA	± NA
Dose-escalation: M7824 1 mg/kg	2.92	± 49.8
Dose-escalation: M7824 3 mg/kg	10.8	± 32.6
Dose-escalation: M7824 10 mg/kg	44.0	± 20.8
Dose-escalation: M7824 20 mg/kg	92.8	± 33.3
Dose-escalation: M7824 30 mg/kg	164	± 31.2
Dose-escalation: M7824 2400 mg/Infusion	219	± 33.9
Dose-expansion: All Solid Tumors 1200mg	75.0	± 42.0
Dose-expansion: NSCLC-2L 500 mg	34.8	± 82.9

Apparent Plasma Clearance (CL) of M7824 Secondary · 0 hours (Pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose

CL is defined as the time it takes for the study drug to be completely removed from the body's plasma.

Group	Value	95% CI
Dose-escalation: M7824 0.3 mg/kg	0.388	± 30.1
Dose-escalation: M7824 1 mg/kg	0.270	± 37.4
Dose-escalation: M7824 3 mg/kg	0.222	± 35.2
Dose-escalation: M7824 10 mg/kg	0.235	± 11.0
Dose-escalation: M7824 20 mg/kg	0.242	± 28.7
Dose-escalation: M7824 30 mg/kg	0.194	± 22.6
Dose-escalation: M7824 2400 mg/Infusion	0.201	± 14.3
Dose-expansion: All Solid Tumors 1200mg	0.219	± 30.6
Dose-expansion: NSCLC-2L 500 mg	0.229	± 38.9

Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 Secondary · Predose, up to Week 52

The detection of antibodies to M7824 was performed using a validated immunoassay method with tiered testing of screening, confirmatory and titration. Number of participants with positive ADA of M7824 were reported.

Group	Value	95% CI
Dose-escalation: M7824 0.3 - 10 mg/kg	1
Dose-escalation: M7824 1 mg/kg	2
Dose-escalation: M7824 1 - 1200 mg	0
Dose-escalation: M7824 3 mg/kg	1
Dose-escalation: M7824 10 mg/kg	1
Dose-escalation: M7824 20 mg/kg	1
Dose-escalation: M7824 30 mg/kg	3
Dose-escalation: M7824 2400 mg/Infusion	1
Dose-escalation: HCC-3 mg/kg	5
Dose-expansion: HCC Ascending Dose 1200mg	8
Dose-expansion: HCC-2L	24
Dose-expansion: Melanoma PD-L1 Fail	8

Adverse events — posted to ClinicalTrials.gov

Time frame: From start of study drug administration up to 200 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dose-escalation: M7824 0.3 - 10 mg/kg

Serious: 2/3 (67%)

Deaths: 2/3

Dose-escalation: M7824 1 mg/kg

Serious: 2/3 (67%)

Deaths: 3/3

Dose-escalation: M7824 1 - 1200 mg

Serious: 2/4 (50%)

Deaths: 4/4

Dose-escalation: M7824 10 mg/kg

Serious: 1/6 (17%)

Deaths: 3/6

Dose-escalation: M7824 20 mg/kg

Serious: 8/10 (80%)

Deaths: 8/10

Dose-escalation: M7824 2400 mg/Infusion

Serious: 2/3 (67%)

Deaths: 2/3

Dose-escalation: M7824 3 mg/kg

Serious: 1/3 (33%)

Deaths: 3/3

Dose-escalation: M7824 30 mg/kg

Serious: 3/7 (43%)

Deaths: 3/7

Dose-expansion: Cervical Cancer

Serious: 12/15 (80%)

Deaths: 8/15

Dose-expansion: Colorectal Carcinoma

Serious: 21/32 (66%)

Deaths: 23/32

Dose-expansion: Esophageal Adenocarcinoma

Serious: 21/30 (70%)

Deaths: 26/30

Dose-expansion: Glioblastoma

Serious: 19/35 (54%)

Deaths: 27/35

Dose-expansion: HCC-2L

Serious: 40/68 (59%)

Deaths: 53/68

Dose-escalation: HCC-3 mg/kg

Serious: 1/6 (17%)

Deaths: 6/6

Dose-expansion: HCC Ascending Dose 1200mg

Serious: 28/38 (74%)

Deaths: 25/38

Dose-expansion: Melanoma PD-L1 Fail

Serious: 14/32 (44%)

Deaths: 25/32

Dose-expansion: NSCLC-2L 1200 mg

Serious: 21/40 (53%)

Deaths: 26/40

Dose-expansion: NSCLC-2L 500 mg

Serious: 17/40 (43%)

Deaths: 30/40

Dose-expansion: NSCLC Biomarker

Serious: 22/41 (54%)

Deaths: 20/41

Dose-expansion: NSCLC PD-L1 Fail

Serious: 49/83 (59%)

Deaths: 73/83

Dose-expansion: Pancreatic Adenocarcinoma

Serious: 29/36 (81%)

Deaths: 29/36

Dose-expansion: Squamous Cell Carcinoma of Head and Neck

Serious: 23/32 (72%)

Deaths: 22/32

Dose-expansion: Triple Negative Breast Cancer

Serious: 19/33 (58%)

Deaths: 26/33

Serious adverse events (249 terms)

Reaction	System	Dose-escalation: M7824 0.3…	Dose-escalation: M7824 1 m…	Dose-escalation: M7824 1 -…	Dose-escalation: M7824 10 …	Dose-escalation: M7824 20 …	Dose-escalation: M7824 240…	Dose-escalation: M7824 3 m…	Dose-escalation: M7824 30 …	Dose-expansion: Cervical C…	Dose-expansion: Colorectal…	Dose-expansion: Esophageal…	Dose-expansion: Glioblastoma	Dose-expansion: HCC-2L	Dose-escalation: HCC-3 mg/kg	Dose-expansion: HCC Ascend…	Dose-expansion: Melanoma P…	Dose-expansion: NSCLC-2L 1…	Dose-expansion: NSCLC-2L 5…	Dose-expansion: NSCLC Biom…	Dose-expansion: NSCLC PD-L…	Dose-expansion: Pancreatic…	Dose-expansion: Squamous C…	Dose-expansion: Triple Neg…
Disease progression	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypercalcaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Malignant pleural effusion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Haematuria	Renal and urinary disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Leukocytosis	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Adrenal insufficiency	Endocrine disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Oesophageal varices haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

Other adverse events (298 terms — click to expand)

Reaction	System	Dose-escalation: M7824 0.3…	Dose-escalation: M7824 1 m…	Dose-escalation: M7824 1 -…	Dose-escalation: M7824 10 …	Dose-escalation: M7824 20 …	Dose-escalation: M7824 240…	Dose-escalation: M7824 3 m…	Dose-escalation: M7824 30 …	Dose-expansion: Cervical C…	Dose-expansion: Colorectal…	Dose-expansion: Esophageal…	Dose-expansion: Glioblastoma	Dose-expansion: HCC-2L	Dose-escalation: HCC-3 mg/kg	Dose-expansion: HCC Ascend…	Dose-expansion: Melanoma P…	Dose-expansion: NSCLC-2L 1…	Dose-expansion: NSCLC-2L 5…	Dose-expansion: NSCLC Biom…	Dose-expansion: NSCLC PD-L…	Dose-expansion: Pancreatic…	Dose-expansion: Squamous C…	Dose-expansion: Triple Neg…
Asthenia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Haemoptysis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypophosphataemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Gamma-glutamyltransferase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Gingival bleeding	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Non-cardiac chest pain	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypercalcaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Hypothyroidism	Endocrine disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Blood bilirubin increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

Most-reported serious reactions: Disease progression, Dyspnoea, Pneumonia, Anaemia, Squamous cell carcinoma of skin, Pulmonary embolism, Abdominal pain, Gastrointestinal haemorrhage.

Data from ClinicalTrials.gov NCT02517398 adverse events section.

Sponsor's own description

The main purpose of this Phase I study was to test MSB0011359C (M7824) at different dose levels to see if it is safe and well tolerated when given once every 2 weeks. Phase I means the study drug has not previously been given to humans or has only been given to a limited number of people, although it has been extensively studied in animals. Based on this information, it is hoped to find out which dose could be best for the treatment of patients. There are two parts of this research study: a dose-escalation part and an expansion part. Dose escalation means that the first people taking part in the study will receive low doses of the study drug, and as more people take part, the additional participants will receive a higher dose. This is done to find the safest dose for the study drug. Expansion means that after the dose-escalation part of the study has looked at the safety and effectiveness of different doses, many more people will be invited to take part in the study and will receive the study drug at the safest dose. Additional purposes of the study are to find out whether the study drug has anti-cancer effects and how the study drug is processed by the body.

Publications & conference data

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

1. TGF-β signaling in health, disease, and therapeutics.
   Deng Z, Fan T, Xiao C, Tian H, et al · · 2024 · cited 737× · PMID 38514615 · DOI 10.1038/s41392-024-01764-w
2. Recent advances in therapeutic strategies for triple-negative breast cancer.
   Li Y, Zhang H, Merkher Y, Chen L, et al · · 2022 · cited 643× · PMID 36038913 · DOI 10.1186/s13045-022-01341-0
3. Next generation of immune checkpoint therapy in cancer: new developments and challenges.
   Marin-Acevedo JA, Dholaria B, Soyano AE, Knutson KL, et al · · 2018 · cited 582× · PMID 29544515 · DOI 10.1186/s13045-018-0582-8
4. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC).
   Cohen EEW, Bell RB, Bifulco CB, Burtness B, et al · · 2019 · cited 528× · PMID 31307547 · DOI 10.1186/s40425-019-0662-5
5. Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy.
   Tang T, Huang X, Zhang G, Hong Z, et al · · 2021 · cited 406× · PMID 33608497 · DOI 10.1038/s41392-020-00449-4
6. Cancer-associated fibroblasts: from basic science to anticancer therapy.
   Yang D, Liu J, Qian H, Zhuang Q. · · 2023 · cited 389× · PMID 37394578 · DOI 10.1038/s12276-023-01013-0
7. Genomic correlates of response to immune checkpoint blockade.
   Keenan TE, Burke KP, Van Allen EM. · · 2019 · cited 367× · PMID 30842677 · DOI 10.1038/s41591-019-0382-x
8. Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, in Advanced Solid Tumors.
   Strauss J, Heery CR, Schlom J, Madan RA, et al · · 2018 · cited 339× · PMID 29298798 · DOI 10.1158/1078-0432.ccr-17-2653