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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02699515
Recruitment Status : Active, not recruiting
First Posted : March 4, 2016
Last Update Posted : August 11, 2020
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Tracking Information
First Submitted Date  ICMJE March 1, 2016
First Posted Date  ICMJE March 4, 2016
Last Update Posted Date August 11, 2020
Actual Study Start Date  ICMJE March 11, 2016
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 3, 2016)
  • Number of subjects with DLT (Dose limiting Toxicity): dose escalation part [ Time Frame: Baseline up to Week 3 ]
    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.
  • Number of Subjects with treatment-emergent adverse events (TEAEs) [ Time Frame: First trial drug administration up to 30 days after the last drug administration assessed up to 2 years ]
    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.
  • Number of subjects with treatment-related Adverse Events (AE) [ Time Frame: First trial drug administration up to 30 days after the last drug administration assessed up to 2 years ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2016)
  • Maximum serum concentration (Cmax) of MSB0011359C [ Time Frame: Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43 ]
  • Minimum serum concentration (Cmin) of MSB0011359C [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43 ]
  • Terminal half life (t1/2) of MSB0011359C [ Time Frame: Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43 ]
  • Serum titers of anti-MSB0011359C antibodies [ Time Frame: 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 [ Time Frame: Date of randomization up to 2 years ]
    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.
  • Best Overall Response (BOR) as assessed by investigator: Expansion part [ Time Frame: Date of randomization up to 2 years ]
    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.
  • Best Overall Response (BOR) as assessed by Independent Endpoint Review Committee (IRC): Expansion part [ Time Frame: Date of randomization up to 2 years ]
    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.
  • Duration of response [ Time Frame: Date of randomization up to 2 years ]
    Time from first assessment of CR to disease progression or death, for TLs, CR was defined as the disappearance of all TLs
  • Disease control rate [ Time Frame: Date of randomization up to 2 years ]
    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.
  • Progression Free survival (PFS) time [ Time Frame: Date of randomization until death or progressive disease assessed up to 2 years ]
    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.
  • Overall Survival (OS) time [ Time Frame: Date of randomization until death assessed up to 2 years ]
    OS is defined as the time from randomization to death due to any cause.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MSB0011359C (M7824) in Subjects With Metastatic or Locally Advanced Solid Tumors
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumors
Intervention  ICMJE Drug: MSB0011359C
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.
Other Name: M7824
Study Arms  ICMJE Experimental: MSB0011359C (M7824)
Intervention: Drug: MSB0011359C
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 13, 2017)
114
Original Estimated Enrollment  ICMJE
 (submitted: March 3, 2016)
111
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan,   Korea, Republic of,   Taiwan
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT02699515
Other Study ID Numbers  ICMJE 200647-0008
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Merck KGaA, Darmstadt, Germany
Study Sponsor  ICMJE Merck KGaA, Darmstadt, Germany
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany
PRS Account Merck KGaA, Darmstadt, Germany
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP