A Study Investigating SGI-110 in Combination With Ipilimumab in Unresectable or Metastatic Melanoma Patients

• Status: Unknown status
• Trial end date: 2018-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Thi pahse I, dose-escalation trial will determine the MTD, safety and the additional benefit achieved from adding SGI-110 to ipilimumab therapy in metastatic melanoma patients. Preclinical evidence generated with SGI-110 in vivo demonstrated that besides having a direct activity on tumor growth as a single agent, SGI-110 was able to "sensitize" neoplastic cells to the anti-tumor activity of CTLA-4 blockade, providing a sound scientific rationale to develop new immunotherapeutic approaches combining SGI-110 with therapeutic mAb to immune check-points.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Italian Network for Tumor Biotherapy Foundation
• Collaborators: Astex Pharmaceuticals; Astex Pharmaceuticals, Inc.
• Treatments: Antibodies, Monoclonal; Azacitidine; Guadecitabine; Ipilimumab

Criteria

Inclusion Criteria:

• Willing and able to give written informed consent

• Unresectable Stage III or Stage IV melanoma with measurable lesions by CT or MRI per mWHO/irRC criteria, that can be amenable to biopsy

• Previously treated or untreated; prior therapy may include chemotherapy or targeted therapy for metastatic disease (i.e., BRAF and/or MAP-ERK kinase (MEK) inhibitor). Prior adjuvant interferon is permitted

• Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

• 4 weeks or greater since last treatment

• Must have recovered from any acute toxicity associated with prior therapy

• Life expectancy greater than 16 weeks

• Negative screening tests for HIV, Hepatitis B, and Hepatitis C

• Women of child-bearing potential must not be pregnant or breastfeeding, must have a negative pregnancy test at Screening and all men must be practicing two medically acceptable methods of birth control. Men should not father a child while receiving treatment with SGI-110 + ipilimumab, and for 2 months following completion of treatment. Men with female partners of childbearing potential should use effective contraception during this time

Exclusion Criteria:

• Subjects with any contraindications for ipilimumab

• Subjects with active brain metastases or leptomeningeal metastases

• Subjects with metastatic uveal melanoma

• Subjects with active, known or suspected autoimmune disease

• Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment

• Subjects with symptomatic effusions on account of pleural, pericardial metastases of melanoma

• Prior treatment with an anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-CTLA-4 antibody

• Subjects who had major surgery or radiation therapy within 21 days of starting treatment

• Subjects who are unable to return for follow-up visits as required by this study

Other Exclusion Criteria:

• Prisoners or subjects who are involuntarily incarcerated

• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.