MC# 14-08 - A Multicenter, Phase I/Ib, Open-Label, Dose-Escalation Study of ABT-165, a Dual Variable Domain Immunoglobulin in Subjects with Advanced Solid Tumors

  • Agent(s): ABT-165
  • Disease Type(s): Bladder, Breast, Cervical, 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
  • Drug Classification(s): Targeted Therapy, Immunotherapy, Monoclonal Antibody
  • Molecular Target(s):

Mechanism of Action

The mechanism of action is not fully understood at this time.

Purpose

In the dose escalation part of this study, the sponsor and investigators want to learn:

  • How the body handles ABT-165
  • How much of ABT-165 can be given safely

In the dose expansion part of this study the sponsor and investigators want to learn:

  • The best way to give ABT-165

In the combination therapy part of this study the sponsor and investigators want to learn:

  • The effectiveness of ABT-165 when given with other chemotherapy regimens and/or ABBV-181
  • The effects of ABT-165 when given with other chemotherapy regimens and/or ABBV-181
Inclusion Criteria
  • Subject must have advanced solid tumor that is not amenable to surgical resection and is not eligible or has refused other approved therapeutic options that have demonstrated clinical benefit.
  • Subject has adequate bone marrow, renal, hepatic and coagulation function.
  • Subject must have measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or disease evaluable by assessment of tumor antigens including but not limited to cancer antigen (CA-125) and prostate-specific antigen (PSA).
  • A negative serum pregnancy test for all WOCBP subjects at the screening visit and a negative urine pregnancy test for all WOCBP subjects at baseline prior to the first dose of study drug.
  • Subjects in the combination therapy cohorts must meet the above inclusion criteria and be eligible to receive paclitaxel or FOLFIRI per most current prescribing information, or at the discretion of the Investigator. Subjects in the combination therapy cohorts who are to receive ABBV-181, an anti-PD1 antibody, must also meet other criteria described in the protocol.
Exclusion Criteria
  • Subject has received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within a period of 21 days or anti-cancer herbal therapy within 7 days prior to Cycle 1 Day 1 of ABT-165.
    • Palliative radiation therapy for bone or skin metastases or subcutaneous metastatic nodules for 10 fractions or less is not subject to a washout period.
    • For approved targeted small molecules, a washout period of 5 half-lives is adequate provided toxicity has resolved as specified in protocol.
    • Subjects who received any agent known to target DLL4 are not eligible.
  • Subject has known uncontrolled metastases to the central nervous system (CNS). Subject with treated brain metastases that are radiographically stable (for at least 4 weeks after therapy) and have no evidence of cavitation or hemorrhage in the brain lesion, are eligible provided that they are asymptomatic and do not require corticosteroids (the subject must have discontinued steroids at least 1 week prior to C1D1).
    • Subject with carcinomatous meningitis or spinal cord compression is not allowed
    • Subject with neurosurgical resection of CNS metastasis within 90 days prior to C1D1 is not allowed
  • Subject has unresolved clinically significant toxicities from prior anticancer therapy, defined as any Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or higher except for alopecia, peripheral neuropathy or anemia.
  • Subject has a clinically significant condition that might put them at higher risk for anti-angiogenic therapy:
    • Symptomatic or persistent, uncontrolled hypertension defined as either systolic blood pressure ≥ 140 or diastolic blood pressure ≥ 90 mmHg.
      • Subjects may be on up to 2 antihypertensive medications to achieve this level of control
      • Combination antihypertensive agents consisting of 2 different medications will be considered as 2-antihypertensives.
      • Subjects must be on stable doses of antihypertensive medications with stable blood pressure in the 7 days prior to the first dose of study drug.
      • Subject may be re-screened if blood pressure is shown to be controlled with or without intervention.
  • Prior history of clinically significant pulmonary hypertension, uncontrolled systemic hypertension or hypertensive crisis, symptomatic heart failure (Heart Association class III – IV), cardiomyopathy, myocardial infarction, unstable/severe angina pectoris, cardiac arrhythmia requiring medication, coronary/peripheral artery bypass graft, aneurysm (considered to be clinically significant) or aneurysm repair, angioplasty, cerebrovascular accident or transient ischemic attack within 5 years of C1D1
  • Left ventricular ejection fraction (LVEF) less than or equal to 50%.
  • Evidence for pulmonary hypertension as defined by peak tricuspid velocity > 2.5 m/s on Doppler echocardiogram.
  • Total cumulative dose of doxorubicin ≥ 400 mg/m2
  • BNP 2X above the normal institutional range (> 200 pg/mL)
  • History of intolerability to prior anti-angiogenic therapy with biologic agents or small molecules
  • Non-healed wound, ulcer or bone fracture
  • Osteonecrosis of the jaw
  • Subject has had major surgery, open biopsy or significant trauma injury within 28 days prior to C1D1 or anticipated to have a major surgical procedure during the course of the study.
  • Subject had minor surgical procedures, such as fine needle aspirations or core biopsies, within 7 days prior to C1D1
  • Subject has radiologic evidence of tumor invading or encasing a major blood vessel.
  • Subject with history of esophageal varices or bleeding peptic ulcer or erosive esophagitis or gastritis < 6 months prior to C1D1
  • Subject has history of significant bleeding (Grade ≥2) < 3 months prior to C1D1
  • Subject has history of DVT or pulmonary embolism < 3 months prior to C1D1
  • Subject has used nonsteroidal anti-inflammatory agent (within 7 days prior to C1D1) or aspiring > 325 mg/day or other agents known to irreversibly inhibit platelet function (within 14 days prior to C1D1) or subject has a condition that requires use of high dose or chronic nonsteroidal anti-inflammatory agent administration.
  • Lung cancer subject with predominantly squamous-cell cancer pathology, central tumor lesions or history of ≥ Grade 2 hemoptysis (≥ ½ tsp bright red blood) within 3 months prior to C1D1
  • Subject has high risk of gastrointestinal perforation or fistula formation in the judgment of the Investigator or Medical Monitor.
  • Subjects enrolled on the combination therapy phase must not meet the above exclusion criteria and must be eligible to receive paclitaxel or FOLFIRI per most current prescribing information, or at the discretion of the Investigator. Subjects receiving ABBV-181 must not meet other exclusion criteria described in the protocol.

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/ct2/show/NCT01946074?term=abt-165&rank=1

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Re: MC# 14-08