Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCSD
Dates
study started
estimated completion

Description

Summary

The purpose of this study is to determine the safety and tolerability of TAK-676 administered as an SA or in combination with pembrolizumab in participants with advanced or metastatic solid tumors.

Official Title

An Open-label, Dose Escalation, Phase 1 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

Keywords

Solid Neoplasms Drug Therapy Pembrolizumab TAK-676

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  2. Life expectancy >12 weeks, as assessed by the investigator.
  3. TAK-676 SA:

o With histologically confirmed (cytological diagnosis is acceptable) advanced or metastatic solid tumors that have no standard therapeutic options or are intolerant to these therapies.

  1. TAK-676 in combination with pembrolizumab:

o With histologically confirmed (cytological diagnosis is acceptable) advanced or metastatic solid tumors, including:

  • Tumors that have relapsed or are refractory to anti-programmed cell death protein 1 (anti-PD-1)/anti-programmed cell death ligand 1 (anti-PD-L1) therapy.
  • Tumors that are naive 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 participant, subsequent participants 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.
  • Must have at least 1 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.

You CAN'T join if...

  1. Corrected QT interval by Fredericia (QTcF) greater than (>) 450 milliseconds (men) or >475 milliseconds (women) on a 12-lead ECG during the screening period.
  2. Grade greater than or equal to (>=) 2 hypotension (that is, hypotension for which nonurgent intervention is required) at screening or during C1D1 predose assessment.
  3. Oxygen saturation less than (<) 92 percent (%) on room air at screening or during C1D1 predose assessment.
  4. Treated with other STING agonists/antagonist and TLR agonists within the past 6 months.
  5. Active vaping within 90 days of C1D1 of study drug(s).
  6. Active smoking.
  7. 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.
  8. History of brain metastasis unless:
  9. Clinically stable (that is, >=6 weeks) following prior surgery, whole-brain radiation, or stereotactic radiosurgery, AND
  10. Off corticosteroids.
  11. Ongoing Grade >= 2 infection or participants with Grade >=2 fever of malignant origin.
  12. . Chronic, active hepatitis (example: participants with known hepatitis B surface antigen seropositive and/or detectable hepatitis C virus [HCV]-RNA).
  13. . For participants in the SA arm only: refusal of standard therapeutic options.
  14. . For participants in the combination arm only: contraindication and/or intolerance to the administration of pembrolizumab.
  15. . 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).
  16. . 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). Participants with clinically relevant ongoing pulmonary complications from prior radiation therapy are not eligible.
  17. . Use of systemic corticosteroids or other immunosuppressive therapy, concurrently or within days of C1D1 of study drug(s), with the following exceptions:
  18. Topical, intranasal, inhaled, ocular, and/or intra-articular corticosteroids.
  19. Physiological doses of replacement steroid therapy (example: for adrenal insufficiency).
  20. . Use of medications that are known clinical OATP1B1 and/or OATP1B3 inhibitors, concurrently or within 14 days of C1D1 of study drug(s).
  21. . Receipt of live attenuated vaccine within 28 days of C1D1 of study drug(s).
  22. . Recipients of allogeneic or autologous stem cell transplantation or organ transplantation.

Locations

  • University of California San Diego Moores Cancer Center
    La Jolla California 92093 United States
  • Providence Portland Medical Center
    Portland Oregon 97213 United States

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
Millennium Pharmaceuticals, Inc.
ID
NCT04420884
Phase
Phase 1
Study Type
Interventional
Last Updated