MSB0011359C (M7824) in Subjects With Metastatic or Locally Advanced Solid Tumors

Study Overview
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Brief Summary
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The main purpose of this study is assess the safety and tolerability of MSB0011359C. Study consists of dose-escalation part and an expansion part in subjects with metastatic or locally advanced solid tumors, for which no standard effective therapy exists or a standard therapy has failed.

Official Title
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A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of MSB0011359C (M7824) in Subjects With Metastatic or Locally Advanced Solid Tumors With Expansion to Selected Indications in Asia

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: MSB0011359C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to give written informed consent and has signed the appropriate written informed consent form (ICF), prior to performance of any trial activities Eligible male and female subjects aged greater than or equal to (>=)20 years Histologically or cytologically proven metastatic or locally advanced solid tumors, for which no effective standard therapy exists or standard therapy has failed Eastern Cooperative Oncology Group performance status (ECOG) performance status of 0 to 1 at trial entry Life expectancy >=12 weeks as judged by the Investigator. Adequate hematological function defined by white blood cell (WBC) count >=3*10^9/Liter with absolute neutrophil count (ANC) >=1.5*10^9/Liter, lymphocyte count >=0.5* 10^9/Liter, platelet count >=75*10^9/Liter, and Hemoglobin (Hgb) >= 9 grams per deciliter (g/dL) (in absence of blood transfusion). Adequate hepatic function defined by a total bilirubin level <=1.5 × Upper limit of normal (ULN), an AST level <= 2.5 × ULN, and an ALT level <= 2.5 × ULN. Adequate renal function defined by an estimated creatinine clearance >50 milliliter per minute (mL/min) according to the Cockcroft-Gault formula or by measure of creatinine clearance from 24 hour urine collection. Other protocol-defined exclusion 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 bone directed radiotherapy), immune therapy, or cytokine therapy Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy) 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 with the exception of cervical carcinoma in situ and superficial or non invasive bladder cancer (treated with curative intent) within the last 5 years or basal cell or squamous cell carcinoma in situ within the last 3 years Rapidly progressive disease which, in the opinion of the Investigator, may predispose to inability to tolerate treatment or trial procedures Active or history of central nervous system metastases, except as in the melanoma-specific Central nervous system (CNS) criteria listed above 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)

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSB0011359C (M7824)<br> | Drug: MSB0011359C<br>* Subjects with metastatic or locally advanced solid tumors will receive intravenous infusion of MSB0011359C over 1 hour once every two weeks for up to 12 months until confirmed progressive disease (PD), unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product (IMP) occurs.<br>* Other names: M7824;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with DLT (Dose limiting Toxicity): dose escalation part | A DLT is defined as any grade greater than or equal to (>=) 3 adverse event suspected to be related to investigational medicinal product (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. | Baseline up to Week 3 | 
| Number of Subjects with treatment-emergent adverse events (TEAEs) | An Adverse Event (AE) is defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) is 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. AEs (SAEs and non-SAEs) will be considered TEAEs when emerging on treatment period defined as the time from the first trial drug administration up to 30 days after the last drug administration date or the earliest date of subsequent anticancer drug therapy minus 1 day, whichever occurs first, unless otherwise stated. | First trial drug administration up to 30 days after the last drug administration assessed up to 2 years | 
| Number of subjects with treatment-related Adverse Events (AE) | Treatment related AEs are any untoward medical occurrence in a subject who received study drug with causal relationship with the investigational product as assessed by the investigator. | First trial drug administration up to 30 days after the last drug administration assessed up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum serum concentration (Cmax) of MSB0011359C |  | Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43 | 
| Minimum serum concentration (Cmin) of MSB0011359C |  | Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43 | 
| Area under the concentration time curve from zero to last sampling time (AUC0-t) of MSB0011359C |  | Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43 | 
| Area under the concentration time curve from time zero to infinity (AUC0-inf) of MSB0011359C |  | Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43 | 
| Terminal half life (t1/2) of MSB0011359C |  | Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43 | 
| Serum titers of anti-MSB0011359C antibodies |  | Predose, Day 15, 43, 85 and every 6-weekly until progression or end of the treatment whichever occur first, assessed up to 3 years | 
| Best Overall Response (BOR) as assessed by investigator: Dose escalation part | BOR will be assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. 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 percent (%) decrease in the sum of largest diameter (SLD) of the TLs, taking as a reference the baseline SLD. | Date of randomization up to 2 years | 
| Best Overall Response (BOR) as assessed by investigator: Expansion part | BOR will be assessed by investigator according to RECIST Version 1.1. BOR is defined as sum of CR and PR. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30 percent (%) decrease in the SLD of the TLs, taking as a reference the baseline SLD. | Date of randomization up to 2 years | 
| Best Overall Response (BOR) as assessed by Independent Endpoint Review Committee (IRC): Expansion part | The BOR per Independent Endpoint Review Committee (IRC) adjudication will be determined according to RECIST 1.1. BOR is defined as sum of CR and PR. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30 percent (%) decrease in the SLD of the TLs, taking as a reference the baseline SLD. | Date of randomization up to 2 years | 
| Duration of response | Time from first assessment of CR to disease progression or death, for TLs, CR was defined as the disappearance of all TLs | Date of randomization up to 2 years | 
| Disease control rate | The disease control rate is defined as the percentage of subjects with BOR. The BOR per IRC adjudication will be determined according to RECIST 1.1. BOR is defined as sum of CR and PR. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline SLD. | Date of randomization up to 2 years | 
| Progression Free survival (PFS) time | PFS is defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PFS will be assessed as RECIST v1.1 as adjudicated by IRC. PD is defined as at least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. | Date of randomization until death or progressive disease assessed up to 2 years | 
| Overall Survival (OS) time | OS is defined as the time from randomization to death due to any cause. | Date of randomization until death assessed up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MSB0011359C