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Completed

NCT Number: NCT02699515

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

The main purpose of this study was to assess the safety and tolerability of MSB0011359C. Study consists of dose-escalation part and an expansion part in participants with metastatic or locally advanced solid tumors, for which no standard effective therapy exists or a standard therapy had failed.

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Key information

Conditions

Solid Tumors

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

NHO Kyushu Cancer Center, Fukuoka, Japan

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Able and willing to give written informed consent and had signed the appropriate written informed consent form (ICF), prior to performance of any trial activities
  • Eligible male and female participants 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 had 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)

Treatment and study plan

MSB0011359C

Drug

Subjects with metastatic or locally advanced solid tumors received 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 names: M7824

Primary outcomes

  1. Number of Participants With Dose Limiting Toxicity (DLT)

    Time frame: Baseline up to Week 3

    A DLT was 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.

  2. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) Version 4.03

    Time frame: First study drug administration up to 30 days after the last drug administration assessed up to approximately 5 years

    An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. 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.

  3. Number of Participants With Treatment-Related Adverse Events (TRAEs) According to NCI-CTCAE Version 4.03

    Time frame: First study drug administration up to 30 days after the last drug administration assessed up to approximately 5 years

    An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. 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. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.

Secondary outcomes

  1. Dose-Escalation Phase: Maximum Serum Concentration (Cmax) of M7824

    Time frame: Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43

    Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.

  2. Dose-Escalation Phase: Terminal Half Life (t1/2) of M7824

    Time frame: Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43

    t1/2 was the time measured for the concentration to decrease by one half, determined as 0.693/Lambda z, here Lambda z was the terminal elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.

  3. Dose-Escalation Phase: Area Under the Serum Concentration Time Curve From Zero to Last Sampling Time (AUC0-t) of M7824

    Time frame: Pre-dose, 0, 4 hour post dose on Day 1, 2, 8, 15, 29, 43

    Area under the serum concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated by linear trapezoidal summation.

  4. Dose-Escalation Phase: Area Under The Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M7824

    Time frame: Pre-dose, 0, 4 hour post dose on Day 1, 2, 8, 15, 29, 43

    The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.

  5. Dose-Escalation Phase: Number of Participants With Positive Serum Titers of Anti-Drug Antibodies of M7824

    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

    The detection of antibodies to M7824 was performed using a validated electrochemiluminescence (ECL) immunoassay with tiered testing of screening, confirmatory and titration. Number of participants with positive anti-drug antibody (ADA) of M7824 were reported.

  6. Dose-Escalation Part: Number of Participants With Best Overall Response (BOR) As Assessed By Investigator

    Time frame: Date of randomization up to 2 years

    BOR was assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. BOR was 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.

  7. Expansion Part: Best Overall Response (BOR) As Assessed By Investigator

    Time frame: Date of randomization up to 2 years

    BOR was assessed by investigator according to RECIST Version 1.1. BOR was 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.

  8. Expansion Part: BOR According to RECIST 1.1 As Adjudicated By The Independent Review Committee (IRC)

    Time frame: Up to 2 years

    The BOR per Independent Endpoint Review Committee (IRC) adjudication was 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.

  9. Expansion Part: Duration of Response (DOR)

    Time frame: Up to 2 years

    Duration of response according to RECIST 1.1 as adjudicated by the IRC was defined as the time from first confirmed response until the first documented disease progression that was subsequently confirmed. It was analyzed using Kaplan-Meier method.

  10. Expansion Part: Disease Control Rate

    Time frame: Up to 2 years

    The disease control rate was defined as the percentage of participants with BOR. The BOR per IRC adjudication was 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.

  11. Expansion Part: Progression Free Survival (PFS) Time

    Time frame: Date of randomization until death or progressive disease assessed up to 2 years

    PFS was 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 was 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.

  12. Expansion Part: Overall Survival (OS) Time

    Time frame: Date of randomization until death assessed up to 2 years

    OS was defined as the time from randomization to death due to any cause.

Sponsors and collaborators

Lead sponsor

Merck KGaA, Darmstadt, Germany

Industry

Registry information

Official study title

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

Important dates

Study start
2016
Primary completion
2022
Study completion
2022
First posted
Mar 4, 2016
Registry last updated
Nov 18, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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