Clinical Trials /

TAK-676 as Single Agent (SA) and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumors

NCT04420884

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: TAK-676 as Single Agent (SA) and in Combination With Pembrolizumab in 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

Clinical Trial IDs

  • ORG STUDY ID: TAK-676-1002
  • SECONDARY ID: U1111-1241-4427
  • NCT ID: NCT04420884

Conditions

  • Solid Neoplasms

Interventions

DrugSynonymsArms
TAK-676Combination Dose Escalation Phase: TAK-676 + Pembrolizumab
PembrolizumabCombination Dose Escalation Phase: TAK-676 + Pembrolizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Monotherapy Dose Escalation Phase: TAK-676 SAExperimentalSafety Lead-in: TAK-676 0.1 milligram (mg), infusion, intravenously, once weekly, on Days 1, 8 and 15 in 21-day treatment Cycles. TAK-676 SA Dose Escalation: TAK-676 SA, infusion, intravenously, once weekly on Days 1, 8 and 15 in each 21-days treatment cycles with escalating dose (0.2 mg and above), for up to 1 year. The dosing will be initiated in the TAK-676 SA Dose Escalation Phase based on the available safety and tolerability data from the Safety Lead-in Phase.
  • TAK-676
Combination Dose Escalation Phase: TAK-676 + PembrolizumabExperimentalTAK-676, infusion, intravenously, once weekly on Days 1, 8 and 15 in each 21-days treatment cycles with escalating dose (0.2 mg and above) plus pembrolizumab 200 mg, infusion, intravenously, once on Day 1 in each 21-days treatment cycles for up to 1 year. The dosing will be initiated based on the available safety and tolerability data from the previous cohort.
  • TAK-676
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          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.

          4. 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.

          5. Adequate bone marrow, renal, hepatic and cardiac functions.

          6. 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.

          7. 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.

          8. 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.

          9. Must have at least 1 RECIST v.1.1-evaluable (measurable or nonmeasurable) lesion.

         10. 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:

          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:

               -  Clinically stable (that is, >=6 weeks) following prior surgery, whole-brain
                  radiation, or stereotactic radiosurgery, AND

               -  Off corticosteroids.

          9. Ongoing Grade >= 2 infection or participants with Grade >=2 fever of malignant origin.

         10. Chronic, active hepatitis (example: participants with known hepatitis B surface
             antigen seropositive and/or detectable hepatitis C virus [HCV]-RNA).

         11. For participants in the SA arm only: refusal of standard therapeutic options.

         12. For participants in the combination arm only: contraindication and/or intolerance to
             the administration of pembrolizumab.

         13. 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).

         14. 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.

         15. Use of systemic corticosteroids or other immunosuppressive therapy, concurrently or
             within 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 (example: for adrenal
                  insufficiency).

         16. Use of medications that are known clinical OATP1B1 and/or OATP1B3 inhibitors,
             concurrently or within 14 days of C1D1 of study drug(s).

         17. Receipt of live attenuated vaccine within 28 days of C1D1 of study drug(s).

         18. Recipients of allogeneic or autologous stem cell transplantation or organ
             transplantation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Based on TEAEs Severity
Time Frame:Up to 30 months
Safety Issue:
Description:A severity grade is defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Grade 1 scales as Mild (asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 scales as Moderate (minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living [ADL]); Grade 3 scales as Severe (severe or medically significant but not immediately life threatening hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 scales as Life-threatening consequences, urgent intervention indicated, and Grade 5 scales as Death related to Adverse Event (AE).

Secondary Outcome Measures

Measure:Cmax: Maximum Observed Plasma Concentration for TAK-676
Time Frame:Cycle 1 Days 1 and 8: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) ]
Safety Issue:
Description:
Measure:Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-676
Time Frame:Cycle 1 Days 1 and 8: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) ]
Safety Issue:
Description:
Measure:AUCt: Area under the Concentration-time Curve From Time 0 to Time t for TAK-676
Time Frame:Cycle 1 Days 1 and 8: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) ]
Safety Issue:
Description:
Measure:AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity for TAK-676
Time Frame:Cycle 1 Days 1 and 8: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) ]
Safety Issue:
Description:
Measure:t1/2: Terminal Disposition Phase Half-life for TAK-676
Time Frame:Cycle 1 Days 1 and 8: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) ]
Safety Issue:
Description:
Measure:CL: Total Clearance After Intravenous Administration for TAK-676
Time Frame:Cycle 1 Days 1 and 8: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) ]
Safety Issue:
Description:
Measure:Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-676
Time Frame:Cycle 1 Days 1 and 8: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) ]
Safety Issue:
Description:
Measure:CLR: Renal Clearance for TAK-676
Time Frame:Cycle 1 Day 1: start of infusion and at multiple time points (up to 24 hours) after end of infusion (Cycle length=21 days)
Safety Issue:
Description:
Measure:Percentage of Dose Excreted in Urine During 24 Hours After Dosing
Time Frame:Cycle 1 Day 1: start of infusion and at multiple time points (up to 24 hours) after end of infusion (Cycle length=21 days)
Safety Issue:
Description:
Measure:CLR/CL%: Renal Clearance as Percentage of Total Clearance for TAK-676
Time Frame:Cycle 1 Day 1: start of infusion and at multiple time points (up to 24 hours) after end of infusion (Cycle length=21 days)
Safety Issue:
Description:
Measure:Overall Response Rate (ORR)
Time Frame:Up to 30 months
Safety Issue:
Description:ORR is defined as the percentage of participants who achieve confirmed complete response (cCR) + confirmed partial response (cPR) during the study in response-evaluable population. ORR will be assessed based on modified Response Evaluation Criteria in Solid Tumor (mRECIST) version 1.1.
Measure:Disease Control Rate (DCR)
Time Frame:Up to 30 months
Safety Issue:
Description:DCR is defined as the percentage of participants who achieve cCR + cPR + stable disease (SD) greater than (>) 6 weeks during the study in response-evaluable population. The DCR will be assessed based on mRECIST v1.1.
Measure:Duration of Response (DOR)
Time Frame:Up to 30 months
Safety Issue:
Description:DOR is the time from the date of first documentation of a cPR or better to the date of first documentation of progressive disease for responders (cPR or better). Responders without documentation of progressive disease will be censored at the date of last response assessment that is SD or better. DOR will be assessed based on mRECIST v1.1.
Measure:Time to Response (TTR)
Time Frame:Up to 30 months
Safety Issue:
Description:TTR is defined as the time from the date of first dose administration to the date of first documented cPR or better by the investigator. TTR will be assessed based on mRECIST v1.1.
Measure:Number of Participants with Upregulation of TAK-676-Induced Stimulator of Interferon Genes (STING)
Time Frame:Up to 30 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Millennium Pharmaceuticals, Inc.

Trial Keywords

  • Drug Therapy

Last Updated

July 2, 2020