Solid Tumors
Conditions
Keywords
Solid tumor, MSB0011359C (M7824), Metastatic or Locally Advanced Solid Tumors, Bintrafusp alfa, INTR@PID
Brief summary
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.
Detailed description
This is a Phase I, open-label, dose-escalation trial with consecutive parallel-group expansion in selected solid tumor indications. The current trial wascomposed of a standard dose escalation 3 + 3 cohort design, for which 3 to 6 subjects will be enrolled at each dose level depending on the occurrence of dose limiting toxicities (DLTs), followed by a consecutive parallel-group expansion in selected solid tumor in dications. Cohorts of 3 subjects with metastatic or locally advanced solid tumors, for which no standard effective therapy exists or standard therapy has failed, will receive MSB0011359C (M7824) at escalating dose levels. After determination of the Maximum tolerated dose (MTD), enrollment in several expansion cohorts will be opened to determine the safety, pharmacokinetic (PK) / Pharmacodynamic, and clinical activity of MSB0011359C (M7824). Subjects who have experienced a confirmed complete response (CR) should continue treatment through the end of 12 months, although additional treatment is possible. In the case of progressive disease (PD), subjects should continue treatment through their next tumor assessment. Additional indications will be planned based on emerging data in the field.
Interventions
DRUGMSB0011359C
Subjects would receive intravenous infusion of MSB0011359C once every 2 weeks in a dose escalation fashion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product (IMP) occurs.
Sponsors
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to understand the purpose of the study, provide signed and dated informed consent, and able to comply with all procedures * In Japan, if a subject is \< 20 years, the written informed consent from his/her parent or guardian will be required in addition to the subject's written consent * Male or female subjects aged greater than or equal to (\>=) 18 years * Life expectancy \>= 12 weeks as judged by the Investigator * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at trial entry * Disease must be measurable with at least 1 uni dimensional measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. * Adequate hematological, hepatic and renal function as defined in the protocol * Effective contraception for both male and female subjects if the risk of conception exists Other protocol-defined inclusion criteria could apply.
Exclusion criteria
* Concurrent treatment with non-permitted drugs and other interventions * Anticancer treatment within 28 days before the start of trial treatment, for example cyto reductive therapy, radiotherapy (with the exception of palliative radiotherapy delivered in a normal organ-spearing technique), immune therapy, or cytokine therapy * Major surgery within 28 days before the start of trial treatment (prior diagnostic biopsy is permitted) * Systemic therapy with immunosuppressive agents within 7 days before the start of trial treatment; or use of any investigational drug within 28 days before the start of trial treatment * Previous malignant disease (other than the target malignancy to be investigated in this trial) within the last 3 years. Subjects with history of cervical carcinoma in situ, superficial or non invasive bladder cancer or basal cell or squamous cell cancer in situ previously treated with curative intent are NOT excluded. Subjects with other localized malignancies treated with curative intent need to be discussed with the Medical Monitor. * Rapidly progressive disease which, in the opinion of the Investigator, may predispose to inability to tolerate treatment or trial procedures * Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded * Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (eg, corneal transplant, hair transplant) Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | 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 after the treatment start date. TEAEs included both serious and non-serious TEAEs. |
| Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | 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. |
| 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 | 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 on Severity having Grade greater than or equal to (\>=) 3 and Grade \>=4 were reported. |
| 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 | 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. |
| Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | 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. |
| Dose-expansion: Disease Control Rate According to Response Assessment in Neuro-Oncology (RANO) as Adjudicated by the IRC for Participants With Glioblastoma | 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 corticosteroids, and stable or increasing clinical status. SD is \<50% decrease in T1 gadolinium enhancing disease but \< 25% increase, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increase in clinical status. PD is ≥25% increase in T1 gadolinium enhancing disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | 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 Investigator. 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. |
| Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | From start of study drug administration up to 200 weeks | An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. TEAEs were defined as events with onset date or worsening during the on-treatment period. Serious Adverse Event (SAE) was 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. Any TEAE included participants with both serious and non-serious AEs. |
| Maximum Concentration (Cmax) of M7824 in Plasma | 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. |
| Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | From start of study drug administration up to 200 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 on Severity having Grade \>= 3 and Grade \>=4 TEAEs were reported. |
| Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | From start of study drug administration up to 200 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. |
| Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824 | 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). |
| Apparent Terminal Half Life (t1/2) of M7824 | 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. |
| Trough Plasma Concentration (Ctrough) of M7824 | 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. |
| Apparent Plasma Clearance (CL) of M7824 | 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. |
| Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 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. |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Japan, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 600 participants were enrolled, randomised and received treatment with M7824 (Bintrafusp alfa).Out of which, 45 participants were included in dose-escalation part at each dose level depending on the occurrence of dose-limiting toxicities and 555 participants in consecutive parallel-group dose-expansion part in selected solid tumor indications.
Participants by arm
| Arm | Count |
|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg Participants received a dose of 0.3 milligram per kilogram (mg/kg) M7824 intravenous (IV) infusion as a first dose and then switched to a 10 mg/kg as a second dose over 1 hour once every 2 weeks in a dose escalation fashion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product (IMP) occurs. | 3 |
| Dose-escalation: M7824 1 mg/kg Participants received a dose of 1 mg/kg M7824 IV infusion over 1 hour once every 2 weeks in a dose escalation fashion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 3 |
| Dose-escalation: M7824 1 - 1200 mg Participants received IV infusion of M7824 1 mg/kg over 1 hour as first dose switched to a 1200 milligram per infusion (mg/infusion) over 1 hour as second dose once every 2 weeks in a dose escalation fashion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 4 |
| Dose-escalation: M7824 3 mg/kg Participants received a dose of 3 mg/kg M7824 IV infusion over 1 hour once every 2 weeks in a dose escalation fashion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 3 |
| Dose-escalation: M7824 10 mg/kg Participants received a dose of 10 mg/kg M7824 IV infusion over 1 hour once every 2 weeks in a dose escalation fashion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 6 |
| Dose-escalation: M7824 20 mg/kg Participants received a dose of 20 mg/kg M7824 IV infusion over 1 hour once every 2 weeks in a dose escalation fashion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 10 |
| Dose-escalation: M7824 30 mg/kg Participants received a dose of 30 mg/kg M7824 IV infusion over 2 hours once every 2 weeks in a dose escalation fashion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 7 |
| Dose-escalation: M7824 2400 mg/Infusion Participants received a flat dose of 2400 mg/infusion M7824 IV infusion over 2 hour once every 2 weeks in a dose escalation fashion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 3 |
| Dose-escalation: HCC-3 mg/kg Participants with Hepatocellular carcinoma (HCC) received a dose of 3 mg/kg M7824 IV infusion over 1 hour once every 2 weeks in a dose escalation fashion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 6 |
| Dose-expansion: HCC Ascending Dose 1200mg Subjects with HCC received a flat ascending dose of 1200 mg M7824 IV infusion once every 2 weeks until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 38 |
| Dose-expansion: HCC-2L Subjects with HCC-2L received a flat dose of 1200 mg M7824 IV infusion once every 2 weeks until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 68 |
| Dose-expansion: Melanoma PD-L1 Fail Participants with Melanoma prior programmed death ligand-1 treatment failure (Melanoma PD-L1 Fail) received a flat dose of 1200 mg M7824 IV infusion once every 2 weeks until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 32 |
| Dose-expansion: NSCLC PD-L1 Fail Participants with Non-small Cell Lung Cancer (NSCLC) PD-L1 Fail (must have received and failed platinum-based chemotherapy and must have received anti-PD-1 or anti-PD-L1 as monotherapy and failed with disease progression) received a flat dose of 1200 mg M7824 IV infusion once every 2 weeks until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 83 |
| Dose-expansion: Pancreatic Adenocarcinoma Participants with Pancreatic Adenocarcinoma received a flat dose of 1200 mg M7824 IV infusion once every 2 weeks until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 36 |
| Dose-expansion: Esophageal Adenocarcinoma Participants with Esophageal Adenocarcinoma received a flat dose of 1200 mg M7824 IV infusion once every 2 weeks until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 30 |
| Dose-expansion: Colorectal Carcinoma Participants with Colorectal Carcinoma received a flat dose of 1200 mg M7824 IV infusion once every 2 weeks until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 32 |
| Dose-expansion: Triple Negative Breast Cancer Participants with Triple Negative Breast Cancer received a flat dose of 1200 mg M7824 IV infusion once every 2 weeks until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 33 |
| Dose-expansion: Glioblastoma Participants with Glioblastoma received a flat dose of 1200 mg M7824 IV infusion once every 2 weeks until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 35 |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck Participants with Squamous Cell Carcinoma of Head and Neck received a flat dose of 1200 mg M7824 IV infusion once every 2 weeks until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 32 |
| Dose-expansion: Cervical Cancer Participants with Cervical Cancer received a flat dose of 1200 mg M7824 IV infusion once every 2 weeks until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 15 |
| Dose-expansion: NSCLC-2L 1200 mg Participants with NSCLC second line (NSCLC-2L) received a flat dose of 1200 mg M7824 IV infusion once every 2 weeks until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 40 |
| Dose-expansion: NSCLC-2L 500 mg Participants with NSCLC-2L received a flat dose of 500 mg M7824 IV infusion once every 2 weeks until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 40 |
| Dose-expansion: NSCLC Biomarker Participants with NSCLC Biomarker (who were naïve to the anti-PD-1/anti-PD-L1 class and had relapsed, refractory, or PD following an anti-PD-1 or anti-PD-L1 agent) received a flat dose of 1200 mg M7824 IV infusion once every 2 weeks until confirmed progression, unacceptable toxicity, or any criterion for withdrawal from the trial or IMP occurs. | 41 |
| Total | 600 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 3 | 4 | 2 | 3 | 8 | 3 | 2 | 6 | 24 | 53 | 25 | 73 | 29 | 26 | 23 | 26 | 25 | 22 | 7 | 26 | 30 | 20 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 2 | 0 | 1 | 1 | 0 | 3 | 1 | 0 | 1 | 0 | 2 |
| Overall Study | Other | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrew Consent | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 7 | 1 | 5 | 4 | 2 | 5 | 4 | 2 | 3 | 2 | 9 | 3 | 1 |
Baseline characteristics
| Characteristic | Dose-expansion: Triple Negative Breast Cancer | Dose-expansion: Glioblastoma | Dose-escalation: M7824 0.3 - 10 mg/kg | Dose-escalation: M7824 1 mg/kg | Dose-escalation: M7824 1 - 1200 mg | Dose-escalation: M7824 3 mg/kg | Dose-expansion: Colorectal Carcinoma | Dose-escalation: M7824 10 mg/kg | Dose-escalation: M7824 20 mg/kg | Dose-escalation: M7824 30 mg/kg | Dose-escalation: M7824 2400 mg/Infusion | Dose-escalation: HCC-3 mg/kg | Dose-expansion: HCC Ascending Dose 1200mg | Dose-expansion: HCC-2L | Dose-expansion: Melanoma PD-L1 Fail | Dose-expansion: NSCLC PD-L1 Fail | Dose-expansion: Pancreatic Adenocarcinoma | Dose-expansion: Esophageal Adenocarcinoma | Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Dose-expansion: Cervical Cancer | Dose-expansion: NSCLC-2L 1200 mg | Dose-expansion: NSCLC-2L 500 mg | Dose-expansion: NSCLC Biomarker | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 5 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 11 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 3 Participants | 15 Participants | 40 Participants | 16 Participants | 37 Participants | 13 Participants | 11 Participants | 10 Participants | 2 Participants | 15 Participants | 21 Participants | 24 Participants | 236 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 30 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 21 Participants | 6 Participants | 9 Participants | 4 Participants | 2 Participants | 3 Participants | 23 Participants | 28 Participants | 16 Participants | 46 Participants | 23 Participants | 19 Participants | 22 Participants | 13 Participants | 25 Participants | 19 Participants | 17 Participants | 364 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 6 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 28 Participants | 3 Participants | 1 Participants | 4 Participants | 3 Participants | 31 Participants | 5 Participants | 9 Participants | 6 Participants | 2 Participants | 3 Participants | 26 Participants | 49 Participants | 26 Participants | 55 Participants | 33 Participants | 27 Participants | 17 Participants | 14 Participants | 39 Participants | 39 Participants | 38 Participants | 481 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 6 Participants | 17 Participants | 6 Participants | 28 Participants | 1 Participants | 3 Participants | 15 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 96 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 11 Participants | 26 Participants | 0 Participants | 11 Participants | 2 Participants | 2 Participants | 5 Participants | 2 Participants | 25 Participants | 15 Participants | 3 Participants | 104 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 7 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 26 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 7 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 25 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 16 Participants | 6 Participants | 28 Participants | 0 Participants | 3 Participants | 11 Participants | 1 Participants | 0 Participants | 0 Participants | 8 Participants | 93 Participants |
| Race (NIH/OMB) White | 18 Participants | 27 Participants | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 29 Participants | 5 Participants | 7 Participants | 5 Participants | 1 Participants | 6 Participants | 13 Participants | 22 Participants | 26 Participants | 40 Participants | 25 Participants | 25 Participants | 12 Participants | 10 Participants | 14 Participants | 25 Participants | 30 Participants | 350 Participants |
| Sex: Female, Male Female | 33 Participants | 11 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 16 Participants | 3 Participants | 5 Participants | 5 Participants | 2 Participants | 0 Participants | 6 Participants | 11 Participants | 13 Participants | 27 Participants | 14 Participants | 2 Participants | 5 Participants | 15 Participants | 7 Participants | 16 Participants | 18 Participants | 217 Participants |
| Sex: Female, Male Male | 0 Participants | 24 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 16 Participants | 3 Participants | 5 Participants | 2 Participants | 1 Participants | 6 Participants | 32 Participants | 57 Participants | 19 Participants | 56 Participants | 22 Participants | 28 Participants | 27 Participants | 0 Participants | 33 Participants | 24 Participants | 23 Participants | 383 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 3 / 3 | 4 / 4 | 3 / 6 | 8 / 10 | 2 / 3 | 3 / 3 | 3 / 7 | 8 / 15 | 23 / 32 | 26 / 30 | 27 / 35 | 53 / 68 | 6 / 6 | 25 / 38 | 25 / 32 | 26 / 40 | 30 / 40 | 20 / 41 | 73 / 83 | 29 / 36 | 22 / 32 | 26 / 33 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 4 / 4 | 6 / 6 | 10 / 10 | 3 / 3 | 3 / 3 | 7 / 7 | 15 / 15 | 32 / 32 | 30 / 30 | 34 / 35 | 66 / 68 | 6 / 6 | 38 / 38 | 31 / 32 | 38 / 40 | 37 / 40 | 41 / 41 | 82 / 83 | 36 / 36 | 31 / 32 | 33 / 33 |
| serious Total, serious adverse events | 2 / 3 | 2 / 3 | 2 / 4 | 1 / 6 | 8 / 10 | 2 / 3 | 1 / 3 | 3 / 7 | 12 / 15 | 21 / 32 | 21 / 30 | 19 / 35 | 40 / 68 | 1 / 6 | 28 / 38 | 14 / 32 | 21 / 40 | 17 / 40 | 22 / 41 | 49 / 83 | 29 / 36 | 23 / 32 | 19 / 33 |
Outcome results
Primary
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
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.
Time frame: From start of study drug administration up to 21 days
Population: DLT Analysis Set included all participants who received all study treatment administrations in the DLT-evaluation period or stopped treatment because of DLTs in the DLT-evaluation period. Data was planned not to be collected and analyzed for the arms: Dose-escalation: M7824 0.3 - 10 mg/kg, Dose-escalation: M7824 1 - 1200 mg and Dose-escalation: HCC-3 mg/kg.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | 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 | 0 Participants |
| Dose-escalation: M7824 1 mg/kg | 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 | 0 Participants |
| Dose-escalation: M7824 1 - 1200 mg | 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 | 0 Participants |
| Dose-escalation: M7824 3 mg/kg | 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 | 1 Participants |
| Dose-escalation: M7824 10 mg/kg | 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 | 0 Participants |
| Dose-escalation: M7824 20 mg/kg | 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 | 0 Participants |
Primary
Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
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 after the treatment start date. TEAEs included both serious and non-serious TEAEs.
Time frame: From start of study drug administration up to 139 weeks
Population: Safety Analysis Set (SAS) included all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 3 Participants |
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 2 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 3 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 2 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 4 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 2 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 3 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 1 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 6 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 1 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 8 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 10 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 3 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 7 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 3 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 2 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 6 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 1 Participants |
Primary
Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death
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.
Time frame: From start of study drug administration up to 139 weeks
Population: SAS included all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAEs | 2 Participants |
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related serious TEAEs | 0 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related serious TEAEs | 0 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAEs | 0 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related serious TEAEs | 0 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAEs | 2 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAEs | 2 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related serious TEAEs | 1 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAEs | 5 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related serious TEAEs | 1 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related serious TEAEs | 3 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAEs | 6 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAEs | 7 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related serious TEAEs | 1 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related serious TEAEs | 1 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAEs | 2 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related serious TEAEs | 0 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAEs | 4 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
Primary
Dose-expansion: Disease Control Rate According to Response Assessment in Neuro-Oncology (RANO) as Adjudicated by the IRC for Participants With Glioblastoma
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 corticosteroids, and stable or increasing clinical status. SD is \<50% decrease in T1 gadolinium enhancing disease but \< 25% increase, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increase in clinical status. PD is ≥25% increase in T1 gadolinium enhancing disease.
Time frame: From date of randomization up to Week 66
Population: FAS included all participants who received at least 1 dose of study treatment. Data was planned, collected and analyzed only for participants with glioblastoma.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose-expansion: Disease Control Rate According to Response Assessment in Neuro-Oncology (RANO) as Adjudicated by the IRC for Participants With Glioblastoma | 22.9 Percentage of participants |
Primary
Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC)
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.
Time frame: From date of randomization up to Week 66
Population: FAS included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Complete response (CR) | 0 Participants |
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Partial response (PR) | 4 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Complete response (CR) | 0 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Partial response (PR) | 6 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Complete response (CR) | 0 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Partial response (PR) | 2 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Complete response (CR) | 0 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Partial response (PR) | 3 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Partial response (PR) | 1 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Complete response (CR) | 0 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Partial response (PR) | 6 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Complete response (CR) | 0 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Complete response (CR) | 0 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Partial response (PR) | 1 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Complete response (CR) | 1 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Partial response (PR) | 2 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Partial response (PR) | 2 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Complete response (CR) | 0 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Partial response (PR) | 4 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Complete response (CR) | 0 Participants |
| Dose-expansion: Cervical Cancer | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Partial response (PR) | 2 Participants |
| Dose-expansion: Cervical Cancer | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Complete response (CR) | 0 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Partial response (PR) | 7 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Complete response (CR) | 0 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Complete response (CR) | 0 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Partial response (PR) | 9 Participants |
| Dose-expansion: NSCLC Biomarker | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Partial response (PR) | 5 Participants |
| Dose-expansion: NSCLC Biomarker | Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC) | Complete response (CR) | 0 Participants |
Primary
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
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 on Severity having Grade greater than or equal to (\>=) 3 and Grade \>=4 were reported.
Time frame: From start of study drug administration up to 139 weeks
Population: SAS included all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | 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 | Grade >= 3 TEAE | 3 Participants |
| Dose-escalation: M7824 0.3 - 10 mg/kg | 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 | Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 0.3 - 10 mg/kg | 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 | Treatment-related Grade >= 3 TEAE | 0 Participants |
| Dose-escalation: M7824 0.3 - 10 mg/kg | 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 | Treatment-related Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 1 mg/kg | 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 | Treatment-related Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 1 mg/kg | 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 | Grade >= 3 TEAE | 3 Participants |
| Dose-escalation: M7824 1 mg/kg | 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 | Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 1 mg/kg | 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 | Treatment-related Grade >= 3 TEAE | 0 Participants |
| Dose-escalation: M7824 1 - 1200 mg | 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 | Grade >= 4 TEAE | 2 Participants |
| Dose-escalation: M7824 1 - 1200 mg | 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 | Treatment-related Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 1 - 1200 mg | 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 | Treatment-related Grade >= 3 TEAE | 0 Participants |
| Dose-escalation: M7824 1 - 1200 mg | 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 | Grade >= 3 TEAE | 2 Participants |
| Dose-escalation: M7824 3 mg/kg | 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 | Grade >= 3 TEAE | 1 Participants |
| Dose-escalation: M7824 3 mg/kg | 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 | Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 3 mg/kg | 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 | Treatment-related Grade >= 3 TEAE | 1 Participants |
| Dose-escalation: M7824 3 mg/kg | 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 | Treatment-related Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 10 mg/kg | 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 | Treatment-related Grade >= 3 TEAE | 2 Participants |
| Dose-escalation: M7824 10 mg/kg | 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 | Grade >= 4 TEAE | 1 Participants |
| Dose-escalation: M7824 10 mg/kg | 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 | Grade >= 3 TEAE | 4 Participants |
| Dose-escalation: M7824 10 mg/kg | 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 | Treatment-related Grade >= 4 TEAE | 1 Participants |
| Dose-escalation: M7824 20 mg/kg | 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 | Treatment-related Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 20 mg/kg | 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 | Grade >= 3 TEAE | 7 Participants |
| Dose-escalation: M7824 20 mg/kg | 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 | Treatment-related Grade >= 3 TEAE | 4 Participants |
| Dose-escalation: M7824 20 mg/kg | 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 | Grade >= 4 TEAE | 2 Participants |
| Dose-escalation: M7824 30 mg/kg | 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 | Treatment-related Grade >= 3 TEAE | 2 Participants |
| Dose-escalation: M7824 30 mg/kg | 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 | Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 30 mg/kg | 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 | Treatment-related Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 30 mg/kg | 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 | Grade >= 3 TEAE | 5 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | 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 | Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | 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 | Treatment-related Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | 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 | Treatment-related Grade >= 3 TEAE | 0 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | 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 | Grade >= 3 TEAE | 2 Participants |
| Dose-escalation: HCC-3 mg/kg | 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 | Grade >= 3 TEAE | 6 Participants |
| Dose-escalation: HCC-3 mg/kg | 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 | Treatment-related Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: HCC-3 mg/kg | 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 | Treatment-related Grade >= 3 TEAE | 0 Participants |
| Dose-escalation: HCC-3 mg/kg | 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 | Grade >= 4 TEAE | 1 Participants |
Secondary
Apparent Plasma Clearance (CL) of M7824
CL is defined as the time it takes for the study drug to be completely removed from the body's plasma.
Time frame: 0 hours (Pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose
Population: Pharmacokinetic Analysis Set included all participants who received at least 1 dose of IMP, and who provided at least 1 post-baseline sample with a measurable concentration of IMP. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure. As per planned analysis combined PK data was collected for the dose cohorts (\[1 mg/kg +1-1200 mg/kg and 3 mg/kg +HCC-3 mg/kg\]) in dose escalation and 1200mg of all solid tumors in dose expansion.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | Apparent Plasma Clearance (CL) of M7824 | 0.388 milliliter per hour per kg(mL/h/kg) | Geometric Coefficient of Variation 30.1 |
| Dose-escalation: M7824 1 mg/kg | Apparent Plasma Clearance (CL) of M7824 | 0.270 milliliter per hour per kg(mL/h/kg) | Geometric Coefficient of Variation 37.4 |
| Dose-escalation: M7824 1 - 1200 mg | Apparent Plasma Clearance (CL) of M7824 | 0.222 milliliter per hour per kg(mL/h/kg) | Geometric Coefficient of Variation 35.2 |
| Dose-escalation: M7824 3 mg/kg | Apparent Plasma Clearance (CL) of M7824 | 0.235 milliliter per hour per kg(mL/h/kg) | Geometric Coefficient of Variation 11 |
| Dose-escalation: M7824 10 mg/kg | Apparent Plasma Clearance (CL) of M7824 | 0.242 milliliter per hour per kg(mL/h/kg) | Geometric Coefficient of Variation 28.7 |
| Dose-escalation: M7824 20 mg/kg | Apparent Plasma Clearance (CL) of M7824 | 0.194 milliliter per hour per kg(mL/h/kg) | Geometric Coefficient of Variation 22.6 |
| Dose-escalation: M7824 30 mg/kg | Apparent Plasma Clearance (CL) of M7824 | 0.201 milliliter per hour per kg(mL/h/kg) | Geometric Coefficient of Variation 14.3 |
| Dose-escalation: M7824 2400 mg/Infusion | Apparent Plasma Clearance (CL) of M7824 | 0.219 milliliter per hour per kg(mL/h/kg) | Geometric Coefficient of Variation 30.6 |
| Dose-escalation: HCC-3 mg/kg | Apparent Plasma Clearance (CL) of M7824 | 0.229 milliliter per hour per kg(mL/h/kg) | Geometric Coefficient of Variation 38.9 |
Secondary
Apparent Terminal Half Life (t1/2) of M7824
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.
Time frame: Pre-dose, 0, 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose
Population: Pharmacokinetic Analysis Set included all participants who received at least 1 dose of IMP, and who provided at least 1 post-baseline sample with a measurable concentration of IMP. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure. As per planned analysis combined PK data was collected for the dose cohorts (\[1 mg/kg +1-1200 mg/kg and 3 mg/kg +HCC-3 mg/kg\]) in dose escalation and 1200mg of all solid tumors in dose expansion.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | Apparent Terminal Half Life (t1/2) of M7824 | 74.0 Hour | Geometric Coefficient of Variation 20.9 |
| Dose-escalation: M7824 1 mg/kg | Apparent Terminal Half Life (t1/2) of M7824 | 120 Hour | Geometric Coefficient of Variation 16.9 |
| Dose-escalation: M7824 1 - 1200 mg | Apparent Terminal Half Life (t1/2) of M7824 | 125 Hour | Geometric Coefficient of Variation 22.6 |
| Dose-escalation: M7824 3 mg/kg | Apparent Terminal Half Life (t1/2) of M7824 | 160 Hour | Geometric Coefficient of Variation 23 |
| Dose-escalation: M7824 10 mg/kg | Apparent Terminal Half Life (t1/2) of M7824 | 172 Hour | Geometric Coefficient of Variation 30.3 |
| Dose-escalation: M7824 20 mg/kg | Apparent Terminal Half Life (t1/2) of M7824 | 171 Hour | Geometric Coefficient of Variation 31.5 |
| Dose-escalation: M7824 30 mg/kg | Apparent Terminal Half Life (t1/2) of M7824 | 177 Hour | Geometric Coefficient of Variation 15.8 |
| Dose-escalation: M7824 2400 mg/Infusion | Apparent Terminal Half Life (t1/2) of M7824 | 152 Hour | Geometric Coefficient of Variation 23.3 |
| Dose-escalation: HCC-3 mg/kg | Apparent Terminal Half Life (t1/2) of M7824 | 145 Hour | Geometric Coefficient of Variation 23.5 |
Secondary
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824
Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (336 hours).
Time frame: 0 hours (pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose post-dose
Population: Pharmacokinetic Analysis Set included all participants who received at least 1 dose of IMP, and who provided at least 1 post-baseline sample with a measurable concentration of IMP. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure. As per planned analysis combined PK data was collected for the dose cohorts (\[1 mg/kg +1-1200 mg/kg and 3 mg/kg +HCC-3 mg/kg\]) in dose escalation and 1200mg of all solid tumors in dose expansion.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824 | 747 hour*microgram per milliliter (h*mcg/ml) | Geometric Coefficient of Variation 25 |
| Dose-escalation: M7824 1 mg/kg | Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824 | 3170 hour*microgram per milliliter (h*mcg/ml) | Geometric Coefficient of Variation 38.6 |
| Dose-escalation: M7824 1 - 1200 mg | Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824 | 11000 hour*microgram per milliliter (h*mcg/ml) | Geometric Coefficient of Variation 33.6 |
| Dose-escalation: M7824 3 mg/kg | Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824 | 32600 hour*microgram per milliliter (h*mcg/ml) | Geometric Coefficient of Variation 10.1 |
| Dose-escalation: M7824 10 mg/kg | Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824 | 62200 hour*microgram per milliliter (h*mcg/ml) | Geometric Coefficient of Variation 31.2 |
| Dose-escalation: M7824 20 mg/kg | Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824 | 114000 hour*microgram per milliliter (h*mcg/ml) | Geometric Coefficient of Variation 9.1 |
| Dose-escalation: M7824 30 mg/kg | Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824 | 144000 hour*microgram per milliliter (h*mcg/ml) | Geometric Coefficient of Variation 14.3 |
| Dose-escalation: M7824 2400 mg/Infusion | Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824 | 60300 hour*microgram per milliliter (h*mcg/ml) | Geometric Coefficient of Variation 27.6 |
| Dose-escalation: HCC-3 mg/kg | Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) of M7824 | 24900 hour*microgram per milliliter (h*mcg/ml) | Geometric Coefficient of Variation 33.7 |
Secondary
Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03
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 on Severity having Grade \>= 3 and Grade \>=4 TEAEs were reported.
Time frame: From start of study drug administration up to 200 weeks
Population: SAS included all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 3 TEAE | 29 Participants |
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 4 TEAE | 11 Participants |
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 3 TEAE | 7 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 3 TEAE | 52 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 3 TEAE | 17 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 4 TEAE | 13 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 4 TEAE | 1 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 3 TEAE | 15 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 3 TEAE | 4 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 4 TEAE | 2 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 4 TEAE | 24 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 4 TEAE | 2 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 3 TEAE | 62 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 3 TEAE | 19 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 3 TEAE | 6 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 4 TEAE | 1 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 3 TEAE | 31 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 4 TEAE | 9 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 3 TEAE | 26 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 4 TEAE | 10 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 3 TEAE | 7 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 3 TEAE | 4 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 4 TEAE | 9 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 4 TEAE | 0 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 3 TEAE | 22 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 3 TEAE | 20 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 4 TEAE | 11 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 3 TEAE | 6 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 4 TEAE | 1 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 4 TEAE | 6 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 3 TEAE | 6 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 3 TEAE | 20 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 4 TEAE | 2 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 3 TEAE | 11 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 3 TEAE | 24 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 4 TEAE | 10 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 4 TEAE | 0 Participants |
| Dose-expansion: Cervical Cancer | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 4 TEAE | 0 Participants |
| Dose-expansion: Cervical Cancer | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 3 TEAE | 3 Participants |
| Dose-expansion: Cervical Cancer | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 4 TEAE | 1 Participants |
| Dose-expansion: Cervical Cancer | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 3 TEAE | 14 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 4 TEAE | 6 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 3 TEAE | 10 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 4 TEAE | 1 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 3 TEAE | 26 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 4 TEAE | 2 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 3 TEAE | 24 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 3 TEAE | 13 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 4 TEAE | 7 Participants |
| Dose-expansion: NSCLC Biomarker | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 4 TEAE | 3 Participants |
| Dose-expansion: NSCLC Biomarker | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 4 TEAE | 10 Participants |
| Dose-expansion: NSCLC Biomarker | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Grade >= 3 TEAE | 27 Participants |
| Dose-expansion: NSCLC Biomarker | Dose Expansion: Number of Participants With TEAEs and Related TEAEs Based on Severity According to NCI-CTCAE Version 4.03 | Treatment-related Grade >= 3 TEAE | 7 Participants |
Secondary
Dose Expansion: Number of Participants With TEAEs and Serious TEAEs
An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. TEAEs were defined as events with onset date or worsening during the on-treatment period. Serious Adverse Event (SAE) was 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. Any TEAE included participants with both serious and non-serious AEs.
Time frame: From start of study drug administration up to 200 weeks
Population: SAS included all randomized participants who received at least 1 dose of IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 28 Participants |
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 38 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 40 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 66 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 14 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 31 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 82 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 49 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 29 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 36 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 21 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 30 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 21 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 32 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 19 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 33 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 34 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 19 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 23 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 31 Participants |
| Dose-expansion: Cervical Cancer | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 12 Participants |
| Dose-expansion: Cervical Cancer | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 15 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 21 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 38 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 37 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 17 Participants |
| Dose-expansion: NSCLC Biomarker | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with Serious TEAEs | 22 Participants |
| Dose-expansion: NSCLC Biomarker | Dose Expansion: Number of Participants With TEAEs and Serious TEAEs | Participants with TEAEs | 41 Participants |
Secondary
Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death
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.
Time frame: From start of study drug administration up to 200 weeks
Population: SAS included all randomized participants who received at least 1 dose of study treatment..
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAEs | 30 Participants |
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-escalation: M7824 0.3 - 10 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related Serious TEAEs | 5 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAEs | 44 Participants |
| Dose-escalation: M7824 1 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related Serious TEAEs | 10 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAEs | 24 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related Serious TEAEs | 4 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related Serious TEAEs | 11 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAEs | 61 Participants |
| Dose-escalation: M7824 3 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAE leading to death | 1 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAEs | 15 Participants |
| Dose-escalation: M7824 10 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related Serious TEAEs | 2 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAEs | 20 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related Serious TEAEs | 4 Participants |
| Dose-escalation: M7824 20 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAEs | 22 Participants |
| Dose-escalation: M7824 30 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related Serious TEAEs | 4 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related Serious TEAEs | 8 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAEs | 25 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAE leading to death | 1 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related Serious TEAEs | 5 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAE leading to death | 1 Participants |
| Dose-escalation: HCC-3 mg/kg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAEs | 25 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related Serious TEAEs | 9 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAEs | 22 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-expansion: Cervical Cancer | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related Serious TEAEs | 3 Participants |
| Dose-expansion: Cervical Cancer | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-expansion: Cervical Cancer | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAEs | 12 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related Serious TEAEs | 3 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAEs | 28 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAEs | 27 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAE leading to death | 0 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related Serious TEAEs | 6 Participants |
| Dose-expansion: NSCLC Biomarker | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAE leading to death | 1 Participants |
| Dose-expansion: NSCLC Biomarker | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related Serious TEAEs | 6 Participants |
| Dose-expansion: NSCLC Biomarker | Dose Expansion: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAE Leading to Death | Treatment-related TEAEs | 31 Participants |
Secondary
Maximum Concentration (Cmax) of M7824 in Plasma
Cmax was obtained directly from the concentration versus time curve.
Time frame: 0 hours (pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose
Population: PK Analysis Set included all who received at least 1 dose of study treatment, and who provided at least 1 post-baseline sample with a measurable concentration. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure. As per planned analysis combined PK data was collected for the dose cohorts (\[1 mg/kg +1-1200 mg/kg and 3 mg/kg +HCC-3 mg/kg\]) in dose escalation and 1200mg of all solid tumors in dose expansion.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | Maximum Concentration (Cmax) of M7824 in Plasma | 7.08 micrograms per milliliter (mcg/ml) | Geometric Coefficient of Variation 9.1 |
| Dose-escalation: M7824 1 mg/kg | Maximum Concentration (Cmax) of M7824 in Plasma | 22.5 micrograms per milliliter (mcg/ml) | Geometric Coefficient of Variation 44.2 |
| Dose-escalation: M7824 1 - 1200 mg | Maximum Concentration (Cmax) of M7824 in Plasma | 92.8 micrograms per milliliter (mcg/ml) | Geometric Coefficient of Variation 74.8 |
| Dose-escalation: M7824 3 mg/kg | Maximum Concentration (Cmax) of M7824 in Plasma | 233 micrograms per milliliter (mcg/ml) | Geometric Coefficient of Variation 9.1 |
| Dose-escalation: M7824 10 mg/kg | Maximum Concentration (Cmax) of M7824 in Plasma | 503 micrograms per milliliter (mcg/ml) | Geometric Coefficient of Variation 15.7 |
| Dose-escalation: M7824 20 mg/kg | Maximum Concentration (Cmax) of M7824 in Plasma | 766 micrograms per milliliter (mcg/ml) | Geometric Coefficient of Variation 8 |
| Dose-escalation: M7824 30 mg/kg | Maximum Concentration (Cmax) of M7824 in Plasma | 943 micrograms per milliliter (mcg/ml) | Geometric Coefficient of Variation 19.7 |
| Dose-escalation: M7824 2400 mg/Infusion | Maximum Concentration (Cmax) of M7824 in Plasma | 411 micrograms per milliliter (mcg/ml) | Geometric Coefficient of Variation 28.5 |
| Dose-escalation: HCC-3 mg/kg | Maximum Concentration (Cmax) of M7824 in Plasma | 185 micrograms per milliliter (mcg/ml) | Geometric Coefficient of Variation 39.7 |
Secondary
Number of Participants With Best Overall Response (BOR) as Assessed by Investigator
BOR according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and as adjudicated by the Investigator. 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.
Time frame: From date of randomization up to Week 66
Population: FAS included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 1 Participants |
| Dose-escalation: M7824 0.3 - 10 mg/kg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-escalation: M7824 1 mg/kg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 0 Participants |
| Dose-escalation: M7824 1 mg/kg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 0 Participants |
| Dose-escalation: M7824 3 mg/kg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 1 Participants |
| Dose-escalation: M7824 3 mg/kg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-escalation: M7824 10 mg/kg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 1 Participants |
| Dose-escalation: M7824 10 mg/kg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 1 Participants |
| Dose-escalation: M7824 20 mg/kg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-escalation: M7824 20 mg/kg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 1 Participants |
| Dose-escalation: M7824 30 mg/kg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 1 Participants |
| Dose-escalation: M7824 30 mg/kg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 1 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 0 Participants |
| Dose-escalation: HCC-3 mg/kg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-escalation: HCC-3 mg/kg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 1 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 5 Participants |
| Dose-expansion: Cervical Cancer | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 9 Participants |
| Dose-expansion: Cervical Cancer | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 1 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 1 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 4 Participants |
| Dose-expansion: NSCLC Biomarker | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 1 Participants |
| Dose-expansion: NSCLC Biomarker | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-expansion: Esophageal Adenocarcinoma | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-expansion: Esophageal Adenocarcinoma | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 4 Participants |
| Dose-expansion: Colorectal Carcinoma | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 1 Participants |
| Dose-expansion: Colorectal Carcinoma | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-expansion: Triple Negative Breast Cancer | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-expansion: Triple Negative Breast Cancer | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 3 Participants |
| Dose-expansion: Glioblastoma | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-expansion: Glioblastoma | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 2 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 5 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-expansion: Cervical Cancer | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-expansion: Cervical Cancer | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 4 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 10 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 1 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 0 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 8 Participants |
| Dose-expansion: NSCLC Biomarker | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Complete response | 1 Participants |
| Dose-expansion: NSCLC Biomarker | Number of Participants With Best Overall Response (BOR) as Assessed by Investigator | Partial response | 4 Participants |
Secondary
Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824
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.
Time frame: Predose, up to Week 52
Population: Immunogenicity Analysis Set included all participants who received at least 1 dose of IMP and who had at least one valid ADA result at any time point.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 1 Participants |
| Dose-escalation: M7824 1 mg/kg | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 2 Participants |
| Dose-escalation: M7824 1 - 1200 mg | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 0 Participants |
| Dose-escalation: M7824 3 mg/kg | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 1 Participants |
| Dose-escalation: M7824 10 mg/kg | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 1 Participants |
| Dose-escalation: M7824 20 mg/kg | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 1 Participants |
| Dose-escalation: M7824 30 mg/kg | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 3 Participants |
| Dose-escalation: M7824 2400 mg/Infusion | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 1 Participants |
| Dose-escalation: HCC-3 mg/kg | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 5 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 8 Participants |
| Dose-expansion: Cervical Cancer | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 24 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 8 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 21 Participants |
| Dose-expansion: NSCLC Biomarker | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 10 Participants |
| Dose-expansion: Esophageal Adenocarcinoma | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 4 Participants |
| Dose-expansion: Colorectal Carcinoma | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 5 Participants |
| Dose-expansion: Triple Negative Breast Cancer | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 7 Participants |
| Dose-expansion: Glioblastoma | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 7 Participants |
| Dose-expansion: Squamous Cell Carcinoma of Head and Neck | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 5 Participants |
| Dose-expansion: Cervical Cancer | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 3 Participants |
| Dose-expansion: NSCLC-2L 1200 mg | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 9 Participants |
| Dose-expansion: NSCLC-2L 500 mg | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 18 Participants |
| Dose-expansion: NSCLC Biomarker | Number of Participants With Positive Anti-Drug Antibody (ADA) of M7824 | 9 Participants |
Secondary
Trough Plasma Concentration (Ctrough) of M7824
Ctrough is the plasma concentration of a drug prior to administration.
Time frame: 0 hours (Pre-dose), 1, 4, 10, 25, 72, 168, 240, 336 hours post-dose
Population: Pharmacokinetic Analysis Set included all participants who received at least 1 dose of IMP, and who provided at least 1 post-baseline sample with a measurable concentration of IMP. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure. As per planned analysis combined PK data was collected for the dose cohorts (\[1 mg/kg +1-1200 mg/kg and 3 mg/kg +HCC-3 mg/kg\]) in dose escalation and 1200mg of all solid tumors in dose expansion.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose-escalation: M7824 0.3 - 10 mg/kg | Trough Plasma Concentration (Ctrough) of M7824 | NA mcg/mL | — |
| Dose-escalation: M7824 1 mg/kg | Trough Plasma Concentration (Ctrough) of M7824 | 2.92 mcg/mL | Geometric Coefficient of Variation 49.8 |
| Dose-escalation: M7824 1 - 1200 mg | Trough Plasma Concentration (Ctrough) of M7824 | 10.8 mcg/mL | Geometric Coefficient of Variation 32.6 |
| Dose-escalation: M7824 3 mg/kg | Trough Plasma Concentration (Ctrough) of M7824 | 44.0 mcg/mL | Geometric Coefficient of Variation 20.8 |
| Dose-escalation: M7824 10 mg/kg | Trough Plasma Concentration (Ctrough) of M7824 | 92.8 mcg/mL | Geometric Coefficient of Variation 33.3 |
| Dose-escalation: M7824 20 mg/kg | Trough Plasma Concentration (Ctrough) of M7824 | 164 mcg/mL | Geometric Coefficient of Variation 31.2 |
| Dose-escalation: M7824 30 mg/kg | Trough Plasma Concentration (Ctrough) of M7824 | 219 mcg/mL | Geometric Coefficient of Variation 33.9 |
| Dose-escalation: M7824 2400 mg/Infusion | Trough Plasma Concentration (Ctrough) of M7824 | 75.0 mcg/mL | Geometric Coefficient of Variation 42 |
| Dose-escalation: HCC-3 mg/kg | Trough Plasma Concentration (Ctrough) of M7824 | 34.8 mcg/mL | Geometric Coefficient of Variation 82.9 |