MC# 17-22 - A Phase I/II, Multicenter, Single-Arm, Open-Label, Dose-Escalation Study of Birinapant in Combination with Pembrolizumab (KEYTRUDA™) in Patients with Relapsed or Refractory Solid Tumors

  • Agent(s): Birinapant, Pembrolizumab
  • Disease Type(s): Bladder, Breast, Cervical, Colorectal, Endometrial, Esophageal, Gastric, Head and Neck, Hepatocellular, Lung-NSCLC, Lung-SCLC, Melanoma, Mesothelioma, Neuroendocrine, Ovarian, Pancreatic, Prostate, Renal, Sarcoma, Solid Tumor, Squamous Cell, Thyroid, Cholangiocarcinoma
  • Phase(s): I, II
  • Drug Classification(s): Targeted Therapy, Small Molecule
  • Molecular Target(s): SMAC, IAP

Mechanism of Action

Birinapant  is a bivalent SMAC mimetic that binds to multiple members of the Inhibitors of Apoptosis proteins (IAP) family.  This action modulates NF-κB signaling and increases NF expression, leading to activation of T-cell and dendritic cell function.

Purpose

In this study, the sponsor and investigators want to learn:

  • The recommended dose of Birinapant that can be given together with Pembrolizumab with an acceptable level of side effects
  • The effects of Birinapant and Pembrolizumab when given in combination
  • How much Birinapant is absorbed into the blood and how fast it is removed
  • How proteins that indicate the status of  disease are affected with use of Birinapant
Inclusion Criteria
  • The patient is male or female ≥ 18 years of age on the day of signing informed consent.
  • Patients with histologically confirmed solid malignancy that is metastatic or unresectable for which standard curative or palliative measures do not exist or are no longer effective
  • Patients with measurable disease according to RECIST v 1.1
  • Patients with Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
  • Patients with normal organ and marrow function
Exclusion Criteria
  • Patients who have received a prior monoclonal antibody, within 4 weeks prior to first dose of study drug.
  • Patienst who have received prior chemotherapy, targeted small molecule therapy or radiotherapy within 2 weeks prior to first dose of study drug.
  • Patients who have received any other investigational agents within 4 weeks of first dose of study drug.
  • Patients who have received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody.
  • Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to birinapant or pembrolizumab or their constituents.
  • Patients with uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia, autoimmune disease or inflammatory diseases, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients with evidence of active, non-infectious pneumonitis or a history of interstitial lung disease.
  • Patients with known history of Human Immunodeficiency Virus (HIV (HIV1/2 antibodies), or Active Hepatitis B (HBsAg reactive. Active Hepatitis C (HCV-RNA qualitative).
  • Patients who are currently breast feeding, pregnant or planning to conceive or father Children from screening through 120 Days after last dose of study drug.

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/ct2/show/NCT02587962?term=NCT02587962&rank=1

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Re: MC# 17-22