Genomic Characterization CS-MATCH-0007 Arm Z1D

The CS-MATCH-0007 protocol is a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and posttreatment tumor biopsy specimens from all patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to their corresponding genomic alterations. Arm Z1D is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with MMR deficiency are treated with nivolumab. This subprotocol is one of the treatment arms in the EAY-131 trial included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood and RNA from tumor tissue. A fuller genomic landscape of tumors from these patients will enable discovery of potential molecular features correlated to clinical outcomes or lay the foundation for future studies leading to new and more effective treatments.

• Study Weblinks:
  • NCI-MATCH Trial
• Study Design:
  • Clinical Trial
• Study Type:
  • Cohort
  • Exome Sequencing
  • RNA Sequencing
• Total number of consented subjects: 36
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• BioSample
• MeSH
• Gene
• PMC
• Clinical Trials
  • NCT02465060

• Patients must fulfill all applicable eligibility criteria outlined in the MATCH Master Protocol.
• Patients must have mismatch repair deficiency as determined via the MATCH Master Protocol.
• Patients must not have known hypersensitivity to nivolumab or compounds of similar chemical or biologic composition.
• No prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40 oranti-CTLA-4 antibodies (or any other antibody targeting T cell co-regulatory pathways).
• Patients with cancers for which nivolumab is approved or becomes approved are excluded.
• Must not have received any of the following therapies within four weeks prior to the first dose of the study drug: IL-2, interferon, or other non-study immunotherapy regimens or immunosuppressive agents. The master protocol eligibility criterion regarding wash-out period from prior therapy is also applicable.
• Must not have a history of toxic epidermal necrolysis (Stevens-Johnson syndrome).
• Must not have received growth factors, including but not limited to granulocyte-colonystimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 2 weeks of study drug administration. Use of such agents while on study is also prohibited. Prior use of growth factors should be documented in the patient's medical history.
• Must not have a history of any autoimmune disease: inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis (e.g., Wegener's Granulomatosis), CNS or motor neuropathy considered to be of autoimmune origin (e.g., Guillian-Barre Syndrome, Myasthenia Gravis, Multiple Sclerosis). Patients are permitted toenroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event). Entry of patients with autoimmune diagnoses not listed here must be approved by the protocol chair.
• Must not be on supplemental home oxygen.
• Must not have evidence of interstitial lung disease
• Patients with a requirement for steroid treatment or other immunosuppressive treatment: Patients will be excluded if they have a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• No history of severe hypersensitivity reaction to any monoclonal antibody.
• Patients with Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection may be eligible provided they have the following:
  • There must be no evidence of clinically significant hepatic injury from hepatitis virus infection.
  • For HBV, patients must be on suppressive therapy and have undetectable HBV viral load.
  • For HCV, patients must either be on suppressive therapy for HCV or have already completed therapy thought to have eradicated HCV.

• Primary Phenotype: Neoplasms
• Turcot syndrome

• MLH1
• MSH2

• Principal Investigator
  • Lyndsay Harris, MD. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
• Funding Sources
  • Division of Cancer Treatment and Diagnosis. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.