Clinical Trials /

Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist) in Patients With Advanced Solid Malignancies

NCT02668770

Description:

The goal of this clinical research study is to find the highest tolerable dose of MGN1703 that can be given in combination with ipilimumab to patients with advanced tumors. The safety of this drug combination will also be studied. This is an investigational study. MGN1703 is not FDA approved or commercially available. It is currently being used for research purposes only. Ipilimumab is FDA approved and commercially available for the treatment of unresectable (cannot be removed with surgery) or metastatic (has spread) melanoma. Up to 60 participants will be enrolled in this study. All will take part at MD Anderson.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist) in Patients With Advanced Solid Malignancies
  • Official Title: A Phase I Trial of Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist) in Patients With Advanced Solid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 2015-0135
  • SECONDARY ID: NCI-2016-00276
  • NCT ID: NCT02668770

Conditions

  • Advanced Cancers
  • Melanoma

Interventions

DrugSynonymsArms
MGN1703Dose Escalation Group: MGN1703 + Ipilimumab
IpilimumabBMS-734016, Yervoy, MDX010Dose Escalation Group: MGN1703 + Ipilimumab

Purpose

The goal of this clinical research study is to find the highest tolerable dose of MGN1703 that can be given in combination with ipilimumab to patients with advanced tumors. The safety of this drug combination will also be studied.

Detailed Description

      Study Groups:

      If you are found to be eligible to take part in this study, you will be assigned to a dose
      level of MGN1703 based on when you joined this study. Up to 4 dose levels of MGN1703 will be
      tested. Up to 6 participants will be enrolled at each dose level. The first group of
      participants will receive the lowest dose level of MGN1703. Each new group will receive a
      higher dose of MGN1703 than the group before it, if no intolerable side effects were seen.
      This will continue until the highest tolerable dose of MGN1703 is found. This is called dose
      escalation.

      In another part of the study (called dose expansion) up to 3 groups of up to 12 additional
      participants will be enrolled. Two (2) groups will receive MGN1703 at the highest tolerable
      dose that was found in dose escalation. One (1) group will receive the first dose level of
      MGN1703 (if it is found to be tolerable). The study doctor will tell you which dose of
      MGN1703 you will receive.

      All participants will receive the same dose level of ipilimumab. You will receive ipilimumab
      at standard doses.

      Study Drug Administration:

      Each study cycle is 21 days.

      You will be given MGN1703 as an injection under the skin on Days 1, 8, and 15 of each cycle.
      Each administration will be between 1-4 injections in multiple parts of your body (such as
      your upper arms and thighs, your abdomen and thighs, or your abdomen and upper arms). The
      study doctor will tell you how many times you will be injected.

      If you are in dose expansion, you may receive MGN1703 as an injection directly into the
      tumor. The study doctor will tell you if you will receive the study drug this way.

      You will also receive ipilimumab by vein over about 90 minutes on Day 8 of Cycles 1-4.

      Study Visits:

      During Week 1 of every cycle, blood (about 1 teaspoon) will be drawn for routine tests.

      During Week 2 of Cycles 1-4, you will have a physical exam.

      During Week 3 of Cycles 1 and 3, blood (about 5 teaspoons) will be drawn for routine tests
      and biomarker testing.

      During Week 3 of Cycles 2 and 4:

        -  Blood (about 5 teaspoons) will be drawn for routine tests and biomarker testing.

        -  Urine will be collected for routine tests.

        -  You will have an EKG.

        -  You will have imaging scans to check the status of the disease.

        -  If you can become pregnant, blood (about 1 teaspoon) will be drawn for a pregnancy
           test.

      If you have melanoma and you are in dose expansion, on Day 1 of Cycle 3 you will have a
      biopsy for biomarker testing (including genetic biomarkers).

      During Cycle 4 and then every even-numbered cycle after that (Cycles 6, 8, 10, and so on):

        -  You will have a physical exam.

        -  Blood (about 5 teaspoons) will be drawn for routine tests and biomarker testing.

        -  You will have imaging scans to check the status of the disease. After 1 year on study,
           you will have these scans every 4 cycles.

      During Cycle 4 and then every 4 cycles after that (Cycles 8, 12, 16, and so on):

        -  Urine will be collected for routine tests.

        -  You will have an EKG.

        -  If you can become pregnant, blood (about 1 teaspoon) will be drawn for a pregnancy
           test.

      Every 30 days for 90 days after your last dose of study drug, you will be called by a member
      of the study staff and asked about any new anticancer drugs you may have started and how you
      are feeling. You may also be asked these questions during a routine clinic visit or this
      information may be collected from your medical record. If you are called, each call should
      last about 10-15 minutes.

      Length of Study:

      You may receive MGN1703 in combination with ipilimumab for up to 4 cycles. After that, you
      may continue taking MGN1703 alone for as long as the doctor thinks it is in your best
      interest. You will no longer be able to take the study drug if the disease gets worse, if
      intolerable side effects occur, or if you are unable to follow study directions.

      You participation on this study will be over 90 days after your last dose of study drug.

      This is an investigational study. MGN1703 is not FDA approved or commercially available. It
      is currently being used for research purposes only. Ipilimumab is FDA approved and
      commercially available for the treatment of unresectable (cannot be removed with surgery) or
      metastatic (has spread) melanoma.

      Up to 60 participants will be enrolled in this study. All will take part at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation Group: MGN1703 + IpilimumabExperimentalParticipants receive MGN1703 on Days 1, 8, and 15 of all cycles as an injection under the skin. Ipilimumab dosed at 3 mg/kg once per cycle on Day 8 following MGN1703 administration. Each cycle is 21 days long. Participants receive a total of 4 treatment cycles for a total of 12 weeks on treatment.
  • MGN1703
  • Ipilimumab
MTD Group: MGN1703 (subcutaneously) + IpilimumabExperimentalDose expansion group consists of participants with advanced malignancy and cutaneous or subcutaneous manifestations. MGN1703 given subcutaneously at MTD from the Dose Escalation Group. Ipilimumab dosed at 3 mg/kg once per cycle on Day 8 following MGN1703 administration. Each cycle is 21 days long.
  • MGN1703
  • Ipilimumab
MTD Group: MGN1703 (intratumoral injection) + IpilimumabExperimentalDose expansion group consists of participants with advanced malignancy and cutaneous or or subcutaneous manifestations. MGN1703 given by intratumoral injection at MTD from the Dose Escalation Group. Ipilimumab dosed at 3 mg/kg once per cycle on Day 8 following MGN1703 administration. Each cycle is 21 days long.
  • MGN1703
  • Ipilimumab
MTD Post XRT Group: MGN1703 (subcutaneously) + IpilimumabExperimentalDose expansion group consists of participants with advanced malignancy treated with radiation (XRT) within the past 2 weeks. MGN1703 given subcutaneously at MTD from the Dose Escalation Group. Ipilimumab dosed at 3 mg/kg once per cycle on Day 8 following MGN1703 administration. Each cycle is 21 days long.
  • MGN1703
  • Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          1. Patients must have a histologically-confirmed metastatic or locally advanced solid
             tumor that has failed to respond to standard therapy, progressed despite standard
             therapy, or for which standard therapy does not exist.

          2. There is no limit on the number of prior treatment regimens.

          3. Patients must be off prior chemotherapy, hormonal therapy, or biological therapy for
             at least 4 weeks or >3 half-lives whichever comes first. Patients with prostate
             cancer may continue to receive LHRH agonist (unless orchiectomy has been performed).

          4. ECOG performance status </= 2 (Karnofsky >60%).

          5. Patients must have adequate organ and marrow function as defined below within 7 days:
             WBC >/= 2500/mm^3. Absolute neutrophil count (ANC) >/= 1,500/mm^3. Absolute
             lymphocyte count (ALC) >/= 1,000/mm^3. Hemoglobin >/= 9g/dl. Platelets >/=
             75,000/mm^3. Creatinine </= 2.0 x ULN or measured CrCl of >/= 50ml/m^2/1.73 m^2.
             Total bilirubin </= 2.0 mg/dL (unless previously diagnosed with Gilbert's Syndrome).
             AST(SGOT)/ALT(SGPT) </= 3 times the institutional upper limit of normal (patients
             with liver involvement will be allowed </= 5.0 X institutional upper normal limit).

          6. Patients must have recovered from toxicity related to prior therapy to at least grade
             1 (defined by CTCAE 4.0) or baseline level. Chronic stable grade 2 peripheral
             neuropathy secondary to neurotoxicity from prior therapies may be considered on a
             case by case basis by the Principal Investigator.

          7. As the effect of these drugs on the developing human fetus is not known, women of
             child-bearing potential and men must agree to use adequate contraception (abstinence;
             hormonal or barrier method of birth control) for the study and at least 2 months
             after completion.

          8. Female patient of childbearing potential has a negative serum pregnancy test within 7
             days of study enrollment.

          9. Patients must be willing and able to review, understand, and provide written consent
             before study enrollment.

         10. Measurable disease as defined by irRC or RECIST 1.1 criteria

         11. Age >/= 18 years.

        Exclusion Criteria:

          1. Severe autoimmune disease: Patients with a history of inflammatory bowel disease
             (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as
             rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus
             Erythematosus or autoimmune vasculitis [e.g., Wegener's Granulomatosis] are excluded
             from this study. Patients with history of mild autoimmune disorders - including but
             not limited to mild psoriasis or Hashimoto's hyperthyroidism may be included at the
             discretion of the principle investigator.

          2. History of acute diverticulitis, intra-abdominal abscess, GI obstruction, abdominal
             carcinomatosis or other known risk factors for bowel perforation.

          3. Any underlying medical or psychiatric condition, which in the opinion of the
             Investigator, will make the administration of study drug hazardous or obscure the
             interpretation of AEs: e.g. a condition associated with frequent diarrhea or chronic
             skin conditions, recent surgery or colonic biopsy from which the patient has not
             recovered, or partial endocrine organ deficiencies.

          4. Current evidence of active and uncontrolled infection, NYHA Class III-IV CHF,
             documented Child's class B-C cirrhosis, active pancreatitis or uncontrolled medical
             disease which in the opinion of the investigator could compromise assessment of
             efficacy.

          5. Known human immunodeficiency virus (HIV)-positive and on highly active antiretroviral
             therapy (HAART), and/or Hepatitis B or C on treatment. Drug interactions between
             those agents and these experimental agents are wholly unknown (screening not
             required).

          6. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             of day 1 of therapy.

          7. Known hypersensitivity to the components of study drugs, its analogs, or drugs of
             similar chemical or biologic composition.

          8. Any non-oncology vaccine therapy used for prevention of infectious diseases (for up
             to one month prior to or after any dose of ipilimumab).

          9. Concomitant therapy with any of the following: IL-2, interferon or other non-study
             immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other
             investigational therapies; or chronic use of systemic corticosteroids (when used in
             the management of cancers other than intracranial glioblastoma, gliosarcoma or
             anaplastic astrocytoma, or when used to treat non-cancer-related illnesses).

         10. Radiation therapy within 4 weeks of study enrollment (exception is radiotherapy
             expansion arm which requires radiation treatment within 2 week period).

         11. Pregnant and breastfeeding women are excluded from this study. Women of child-bearing
             potential and men must agree to use contraception prior to study entry and for the
             duration of study participation. Should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician.

         12. Use of any other concurrent investigational agents or anticancer agents including
             hormonal therapy, except in the case of prostate cancer patients who are being
             treated with LHRH agonist at the time of trial entry.

         13. Previous exposure to TLR agonist therapy.

         14. Known history of plasma cortisol and adrenocorticotropic hormone (ACTH) levels
             consistent with adrenal failure.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) of MGN1703 with Ipilimumab
Time Frame:84 days
Safety Issue:
Description:If more than or equal to one third of the participants at a dose level experience dose limiting toxicity (DLT), the MTD reassessed and the next lowest dose level for the combination therapy considered the MTD.

Secondary Outcome Measures

Measure:Tumor Response
Time Frame:84 days
Safety Issue:
Description:Tumor response defined as one or other of the following: (1) stable disease for more than than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by irRC criteria.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Advanced Cancers
  • Melanoma
  • Advanced solid malignancies
  • Metastatic
  • MGN1703
  • Ipilimumab
  • Yervoy
  • BMS-734016
  • MDX010
  • Refractory
  • Relapsed

Last Updated

March 6, 2017