Description:
The main purpose of this Phase I study is 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.
Title
- Brief Title: MSB0011359C (M7824) in Metastatic or Locally Advanced Solid Tumors
- Official Title: A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, PK, Biological and Clinical Activity of MSB0011359C in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications
Clinical Trial IDs
- ORG STUDY ID:
EMR 200647-001
- SECONDARY ID:
2015-004366-28
- NCT ID:
NCT02517398
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| MSB0011359C | M7824 | MSB0011359C (M7824) |
Purpose
The main purpose of this Phase I study is 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 is composed 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 indications. 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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| MSB0011359C (M7824) | Experimental | | |
Eligibility Criteria
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 exclusion criteria could apply
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Dose-escalation Part: Number of Subjects With Treatment Emergent Adverse Events (TEAEs) |
| Time Frame: | Up to 10 weeks after last treatment |
| Safety Issue: | |
| Description: | 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. 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 10 weeks after the last drug administration date. |
Secondary Outcome Measures
| Measure: | Dose Escalation and Expansion Part: Maximum Concentration (Cmax) of MSB0011359C in Plasma |
| Time Frame: | Predose, 0, 4, and 30 hours post dose |
| Safety Issue: | |
| Description: | |
| Measure: | Dose Escalation and Expansion Part: Minimum Concentration (Cmin) of MSB0011359C in Plasma |
| Time Frame: | Predose, 0, 4, and 30 hours post dose |
| Safety Issue: | |
| Description: | |
| Measure: | Dose Escalation and Expansion Part: Area Under the Plasma Concentration Time Curve From Zero to Last Sampling Time (AUC0-t) of MSB0011359C |
| Time Frame: | Predose, 0, 4, and 30 hours post dose |
| Safety Issue: | |
| Description: | |
| Measure: | Dose Escalation and Expansion Part: Terminal Half Life (t1/2) of MSB0011359C |
| Time Frame: | Predose, 0, 4, and 30 hours post dose |
| Safety Issue: | |
| Description: | |
| Measure: | Dose Escalation and Expansion Part: Serum Titers of Anti-MSB0011359C Antibodies |
| Time Frame: | Predose, Day 15, Day 43, Day 85 and every 6-weekly until progression or end of the treatment whichever occur first, assessed up to Week 52 |
| Safety Issue: | |
| Description: | |
| Measure: | Dose Escalation and Expansion Part: Best Overall Response (BOR) as Assessed by Investigator |
| Time Frame: | Date of randomization up to Week 52 |
| Safety Issue: | |
| Description: | BOR according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and as adjudicated by the Investigator.The BOR per investigator adjudication will be determined according to RECIST 1.1 and modified immune related response criteria (irRC), respectively. 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. Overall immune-related complete response: Complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to 10 mm or less. Overall immune-related partial response (irPR): Sum of the longest diameters of target and new measurable lesions decreases >= 30%. |
| Measure: | Dose Expansion Part: Number of Subjects With Treatment Emergent Adverse Events (TEAEs) |
| Time Frame: | Time from the first trial drug administration up to 10 weeks last drug administration date |
| Safety Issue: | |
| Description: | 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. 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 29 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. |
| Measure: | Dose Expansion Part: Number of Subjects With Treatment-Related AEs |
| Time Frame: | Time from the first trial drug administration up to 10 weeks after the last drug administration date |
| Safety Issue: | |
| Description: | 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. AEs will be assessed according to severity; mild (not causing any significant problem, dose adjustment not required), moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event) and severe (caused problem that interferes significantly with usual activities or the clinical status, study drug stopped due to adverse event). |
| Measure: | Dose Expansion Part: Number of Treatment Emergent Adverse Events (TEAEs) and Related TEAEs by Severity |
| Time Frame: | Time from the first trial drug administration up to 10 weeks after the last drug administration date |
| Safety Issue: | |
| Description: | |
| Measure: | Dose Expansion Part: Duration of Treatment Emergent Adverse Events (TEAEs) and Related TEAEs |
| Time Frame: | Time from the first trial drug administration up to 10 weeks after the last drug administration date |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | EMD Serono Research & Development Institute, Inc. |
Trial Keywords
- Solid tumor
- MSB0011359C (M7824)
- Metastatic or Locally Advanced Solid Tumors
- Bintrafusp alfa
- INTR@PID
Last Updated
March 22, 2021
