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

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ClinicalTrials.gov Identifier: NCT02668770
Recruitment Status : Recruiting
First Posted : January 29, 2016
Last Update Posted : October 5, 2018
Sponsor:
Collaborator:
Mologen AG
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Advanced Cancers Melanoma Drug: MGN1703 Drug: Ipilimumab Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial of Ipilimumab (Immunotherapy) and MGN1703 (TLR Agonist) in Patients With Advanced Solid Malignancies
Actual Study Start Date : May 11, 2016
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2019


Arm Intervention/treatment
Experimental: Dose Escalation Group: MGN1703 + Ipilimumab

Participants 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.

Drug: MGN1703

Dose Escalation Group Starting Dose: 15 mg on Days 1, 8, and 15 of each 21 day cycle.

Dose Expansion Group Starting Dose: Maximum tolerated dose from Dose Escalation Group.


Drug: Ipilimumab
Dose Escalation and Dose Expansion Group Dose: 3 mg/kg by vein on Day 8 of a 21 day cycle.
Other Names:
  • BMS-734016
  • Yervoy
  • MDX010

Experimental: MTD Group: MGN1703 (subcutaneously) + Ipilimumab

Dose 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.

Drug: MGN1703

Dose Escalation Group Starting Dose: 15 mg on Days 1, 8, and 15 of each 21 day cycle.

Dose Expansion Group Starting Dose: Maximum tolerated dose from Dose Escalation Group.


Drug: Ipilimumab
Dose Escalation and Dose Expansion Group Dose: 3 mg/kg by vein on Day 8 of a 21 day cycle.
Other Names:
  • BMS-734016
  • Yervoy
  • MDX010

Experimental: MTD Group: MGN1703 (intratumoral injection) + Ipilimumab

Dose 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.

Drug: MGN1703

Dose Escalation Group Starting Dose: 15 mg on Days 1, 8, and 15 of each 21 day cycle.

Dose Expansion Group Starting Dose: Maximum tolerated dose from Dose Escalation Group.


Drug: Ipilimumab
Dose Escalation and Dose Expansion Group Dose: 3 mg/kg by vein on Day 8 of a 21 day cycle.
Other Names:
  • BMS-734016
  • Yervoy
  • MDX010

Experimental: MTD Post XRT Group: MGN1703 (subcutaneously) + Ipilimumab

Dose 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.

Drug: MGN1703

Dose Escalation Group Starting Dose: 15 mg on Days 1, 8, and 15 of each 21 day cycle.

Dose Expansion Group Starting Dose: Maximum tolerated dose from Dose Escalation Group.


Drug: Ipilimumab
Dose Escalation and Dose Expansion Group Dose: 3 mg/kg by vein on Day 8 of a 21 day cycle.
Other Names:
  • BMS-734016
  • Yervoy
  • MDX010




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of MGN1703 with Ipilimumab [ Time Frame: 84 days ]
    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 :
  1. Tumor Response [ Time Frame: 84 days ]
    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.



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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. 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) >/= 500/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.

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): NCT02668770


Contacts
Contact: David S. Hong, MD 713-563-1930

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Mologen AG
Investigators
Principal Investigator: David S. Hong, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02668770     History of Changes
Other Study ID Numbers: 2015-0135
NCI-2016-00276 ( Registry Identifier: NCI CTRP )
First Posted: January 29, 2016    Key Record Dates
Last Update Posted: October 5, 2018
Last Verified: October 2018

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

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs