MC# 20-08 - An Open-label, Dose Escalation, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-676 as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Advanced or Metastatic Solid Tumors

  • Agent(s): TAK-676
  • Disease Type(s): Solid Tumor
  • Phase(s): I
  • Drug Classification(s): Targeted Therapy, Immunotherapy
  • Molecular Target(s): STING

Mechanism of Action

N/A

Purpose

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

  • How much of TAK-676 can be given with an acceptable level of side effects
  • About the safety and tolerability of TAK-676 alone and in combination with Pembrolizumab
  • How proteins that indicate the status of your immune system are affected with use of TAK-676 alone and in combination with Pembrolizumab
  • If TAK-676 alone and in combination with Pembrolizumab prevents or delays tumor growth or shrinks existing tumors
  • How quickly TAK-676 is removed from your blood stream
Inclusion Criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Life expectancy >12 weeks, as assessed by the investigator
  • TAK-676 SA:
    • Patients with histologically confirmed (cytological diagnosis is acceptable) advanced or metastatic solid tumors that have no standard therapeutic options or are intolerant to these therapies
  • TAK-676 in combination with pembrolizumab:
    • Patients with histologically confirmed (cytological diagnosis is acceptable) advanced or metastatic solid tumors, including:
      • Tumors that have relapsed or are refractory to anti-PD-1/anti-PD-L1 therapy
      • Tumors that are naïve to anti-PD-1/anti-PD-L1 therapy
  • Adequate bone marrow, renal, hepatic and cardiac functions
  • Left ventricular ejection fraction (LVEF) >50%, as measured by echocardiogram or multiple-gated acquisition (MUGA) scan within 4 weeks before receiving the first dose of study drug
  • Clinically significant toxic effects of previous therapy have recovered to Grade 1 (per NCI CTCAE Version 5.0) or baseline, except for alopecia, Grade 2 peripheral neuropathy, and/or autoimmune endocrinopathies with stable endocrine replacement therapy
  • Once peripheral evidence of TAK-676 pharmacodynamic stimulation of the innate and/or adaptive immune system is observed in the blood and/or clinical response (CR/PR) is observed in at least 1 patient, subsequent patients must:
    • Have at least 1 lesion amenable for biopsy.
    • Agree to have 2 tumor biopsies: 1 during the screening period and 1 while on TAK-676 treatment
  • Patients must have at least 1 Response Evaluation Criteria in Solid Tumor (RECIST) v.1.1– evaluable (measurable or nonmeasurable) lesion
  • PK/pharmacodynamic blood must be drawn on a peripherally-inserted catheter. TAK-676 is preferentially administered through a central line, but peripheral infusion is acceptable.  If a peripheral line is used for TAK-676 and/or pembrolizumab infusion, it must be separate than the one used for PK/pharmacodynamic collection.
Exclusion Criteria
  • Corrected QT interval by Fredericia (QTcF) greater than (>) 450 milliseconds (men) or >475 milliseconds (women) on a 12-lead ECG during the screening period
  • Grade greater than or equal to (>=) 2 hypotension (that is, hypotension for which nonurgent intervention is required) at screening or during C1D1 predose assessment
  • Oxygen saturation less than (<) 92 percent (%) on room air at screening or during C1D1 predose assessment
  • Patients treated with other STING agonists/antagonist and TLR agonists within the past 6 months
  • Active smoking
  • Active vaping within 90 days of C1D1 of study drug(s)
  • Current history of pneumonitis, interstitial lung disease, severe Chronic Obstructive Pulmonary Disease (COPD), idiopathic pulmonary fibrosis, other restrictive lung diseases, acute pulmonary embolism, or Grade ≥2 pleural effusion or ascites not controlled by tap or requiring indwelling catheters
  • History of brain metastasis unless:
    • Clinically stable (that is , >=6 weeks) following prior surgery, whole-brain radiation, or stereotactic radiosurgery, AND
    • Off corticosteroids
  • Ongoing Grade >= 2 infection or patients with Grade ≥2 fever of malignant origin
  • Known history of uncontrolled autoimmune disorders, HIV infection, or other relevant congenital or acquired immunodeficiencies
  • Chronic, active hepatitis (eg, patients with known hepatitis B surface antigen seropositive and/or detectable hepatitis C virus [HCV]-RNA)
  • For patients in the SA arm only: refusal of standard therapeutic options
  • For patients in the combination arm only: contraindication and/or intolerance to the administration of pembrolizumab
  • Concurrent chemotherapy, immunotherapy (except for pembrolizumab in the combination arm), biologic, or hormonal therapy (except for adjuvant endocrine therapy for a history of breast cancer)
  • Concurrent use of hormones for noncancer-related conditions is acceptable (except for corticosteroid hormones)
  • Radiation therapy within 14 days (42 days for radiation to the lungs) and/or systemic treatment with radionuclides within 42 days before C1D1 of study drug(s).  Patients with clinically relevant ongoing pulmonary complications from prior radiation therapy are not eligible.
  • Use of systemic corticosteroids or other immunosuppressive therapy, concurrently or within 14 days of C1D1 of study drug(s), with the following exceptions:
    • Topical, intranasal, inhaled, ocular, and/or intra-articular corticosteroids
    • Physiological doses of replacement steroid therapy (eg, for adrenal insufficiency)
  • Use of medications that are known clinical OATP1B1 and/or OATP1B3 inhibitors, concurrently or within 14 days of C1D1 of study drug(s)
  • Receipt of live attenuated vaccine within 28 days of C1D1 of study drug(s)
  • Recipients of allogeneic or autologous stem cell transplantation or organ transplantation

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City

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Re: MC# 20-08