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M7824 in Consensus Molecular Subtype 4, Treatment-Refractory Metastatic Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT03436563
Recruitment Status : Recruiting
First Posted : February 16, 2018
Last Update Posted : February 19, 2019
Sponsor:
Collaborator:
EMD Serono
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn about the safety of giving M7824 to patients with a certain type of colorectal cancer (Consensus Molecular Subtype 4 [CMS4]). Researchers also want to learn if the study drug can help to control the disease.

This is an investigational study. M7824 is not FDA approved or commercially available. It is currently being used for research purposes only.

The study doctor can explain how the study drug is designed to work.

Up to 59 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Adenocarcinoma of the Colon Adenocarcinoma of the Rectum Drug: M7824 Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 59 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Trial of M7824 in Solid Tumors With Microsatellite Instability or With Consensus Molecular Subtype 4 Metastatic Colorectal Cancer
Actual Study Start Date : March 7, 2018
Estimated Primary Completion Date : November 29, 2019
Estimated Study Completion Date : November 29, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort A: MSI-H mCRC
M7824 administered intravenously at a dose of 1200 mg every 14 days. M7824 administered until documented PD, unacceptable toxicity, or withdrawal of informed consent.
Drug: M7824
M7824 administered intravenously at a dose of 1200 mg every 14 days
Other Name: MSB0011359C

Experimental: Cohort B: CMS4 mCRC
M7824 administered intravenously at a dose of 1200 mg every 14 days. M7824 administered until documented PD or unacceptable toxicity, or withdrawal of informed consent.
Drug: M7824
M7824 administered intravenously at a dose of 1200 mg every 14 days
Other Name: MSB0011359C

Experimental: Cohort C: Non-CRC MSI-H Solid Tumors
M7824 administered intravenously at a dose of 1200 mg every 14 days. M7824 administered until documented PD, unacceptable toxicity, or withdrawal of informed consent.
Drug: M7824
M7824 administered intravenously at a dose of 1200 mg every 14 days
Other Name: MSB0011359C




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Baseline up to 12 months ]
    ORR confirmed according to RECIST 1.1.


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: Baseline up to 2 years ]
    PFS determined according to RECIST 1.1.

  2. Overall Survival (OS) [ Time Frame: Baseline up to 2 years ]
  3. Adverse Events of Treatment with M7824 [ Time Frame: Start of study treatment up to 28 days after end of treatment ]
    Adverse events confirmed per NCI-CTCAE v4.03.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed adenocarcinoma of the colon or the rectum that is metastatic or unresectable.
  2. Confirmation of: a) Cohort A: MSI-H CRC either by IHC for loss of protein expression in one of 4 mismatch repair proteins (MLH1, mutS homologue 2 (MSH2), mutS homolog 6 (MSH6), PMS2) or by detection of microsatellites within the tumor DNA as per institutional practices; b) Cohort B: CMS4 CRC classification on pretreatment primary tumor; c) Cohort C: MSI-H non-CRC solid tumor either by IHC for loss of protein expression in one of 4 mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) or by detection of microsatellites within the tumor DNA as per institutional practices.
  3. Age >18 years at time of study entry.
  4. Ability to provide written informed consent.
  5. Documented progression to prior therapies: a) Cohort A: Disease progression following prior immune checkpoint blockade therapy; b) Cohort B: Progression or intolerance to at least 2 prior lines of standard therapy for unresectable or metastatic CRC; c) Cohort C: Disease progression following prior immune checkpoint blockade therapy.
  6. Available primary tumor tissue for CMS4 biomarker assessment.
  7. Life expectancy =/>12 weeks as judged by the treating physician.
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  9. Measurable disease according to RECIST v1.1.
  10. Adequate hematological function, defined by white blood cell (WBC) count =/> 3 × 10^9/L with absolute neutrophil count (ANC) =/> 1.5 × 10^9/L, lymphocyte count =/> 0.5 × 10^9/L, platelet count =/>100 × 10^9/L, and Hgb =/> 9 g/dL (in absence of blood transfusion).
  11. Adequate hepatic function defined by a total bilirubin level =/< 1.5 × the upper limit of normal (ULN), an AST, level =/< 2.5 × ULN, and an ALT level =/< 2.5 × ULN.
  12. International normalized ratio (INR) < 1.5.
  13. Adequate renal function defined by an estimated creatinine clearance >30 mL/min according to the Cockcroft-Gault formula or be measure for creatinine clearance from 24 hour urine collection.
  14. Highly effective contraception for both male and female subjects if the risk of conception exists. Highly effective contraception must be used 30 days prior to first trial administration, for the duration of trial treatment, and at least for 4 months after stopping trial treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the treating physician should be informed immediately.

Exclusion Criteria:

  1. Concurrent treatment with non-permitted drugs and other interventions.
  2. Anticancer treatment within 14 days before the start of trial treatment [e.g., cytoreductive therapy, radiotherapy (with the exception of palliative radiotherapy delivered in a normal organ-sparing technique), immune therapy, or cytokine therapy].
  3. Major surgery as determined by the investigator within 28 days before the start of trial treatment (prior diagnostic biopsy is permitted).
  4. Systemic therapy with immunosuppressive agents within 7 days before the start of treatment; or use of any investigational drug within 28 days before the start of trial treatment.
  5. Cohort A and C only: Intolerance or serious adverse immune related adverse events (irAEs) that were symptomatic or required or continues to require ongoing immunosuppression to previous immune checkpoint therapy.
  6. Cohort B only: prior exposure to any immune checkpoint blockade agent or any other immunomodulatory agent used for antineoplastic therapy for mCRC.
  7. Previous malignant disease (other than the target malignancy to be investigated in this trial) within 3 years prior to study treatment initiation. Subjects with a history of cervical carcinoma in situ, superficial or non-invasive bladder cancer, or basal cell or squamous cell carcinoma 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 Principal investigator.
  8. Subjects with active central nervous system (CNS) metastases are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy.
  9. Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant).
  10. Significant acute or chronic infections including, among others: a) Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome; b) HBV or HCV infection (HBV surface antigen positive and HBV core antibody positive with reflex to positive HBV DNA or HBV core antibody positive alone with reflex to positive HBV DNA or positive HCV antibody with reflex to positive HCV RNA); c) Subjects with active tuberculosis (history of exposure or history of positive tuberculosis test plus presence of clinical symptoms, physical or radiographic findings).
  11. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent: a) Subjects with type I diabetes, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible; b) Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses =/< 10mg of prednisone or equivalent per day; c) Administration of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable.
  12. Known severe hypersensitivity reactions to monoclonal antibodies (Grade =/> 3 NCI-CTCAE v4.03), any history of anaphylaxis, or recent (within 5 months) history of uncontrolled asthma.
  13. Persisting toxicity (except alopecia and vitiligo) related to prior oncologic therapy Grade >1 NCI-CTCAE v4.03, however, sensory neuropathy Grade =/< 2 is acceptable.
  14. Clinically significant cardiovascular/ cerebrovascular disease as follows: cerebral vascular accident / stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class >II), or serious cardiac arrhythmia.
  15. Clinically relevant diseases (for example, inflammatory bowel disease) and / or uncontrolled medical conditions, which, in the opinion of the Investigator, might impair the subject's tolerance or ability to participate in the trial.
  16. Vaccine administration within 4 weeks of M7824 administration. Vaccination with live vaccines while on trial is prohibited. Administration of inactivated vaccines is allowed (for example, inactivated influenza vaccines).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03436563


Contacts
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Contact: Van K. Morris, MD 713-792-2828 vkmorris@mdanderson.org

Locations
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United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact       vkmorris@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
EMD Serono
Investigators
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Principal Investigator: Van K. Morris, MD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03436563     History of Changes
Other Study ID Numbers: 2017-0339
NCI-2018-00919 ( Registry Identifier: NCI CTRP )
First Posted: February 16, 2018    Key Record Dates
Last Update Posted: February 19, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Adenocarcinoma of the colon
Adenocarcinoma of the rectum
Microsatellite instability-high metastatic colorectal cancer
Treatment-refractory, consensus molecular subtype 4 (CMS4) mCRC
MSI-H non CRC solid tumors who have progressed on immune checkpoint blockade therapy
M7824
MSB0011359C

Additional relevant MeSH terms:
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Colorectal Neoplasms
Adenocarcinoma
Rectal Neoplasms
Microsatellite Instability
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Genomic Instability
Pathologic Processes