A Study of TAK-188 in Adults With Advanced or Spreading Solid Tumors
ConditionAdvanced or Metastatic Solid Tumors
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorTakeda
About this trial
TAK-188 is a new medicine that targets a protein called CCR8, which is found on the surface of certain cells (Tregs) inside tumors. These cells can weaken the body's ability to fight cancer. TAK-188 may help to remove these Tregs. Removing these Tregs may allow more cancer-fighting cells (CD8+ T cells) to attack the tumor and potentially stop tumors from growing.
In this study, researchers want to learn if TAK-188 can help the body's immune system better fight cancer in adults with advanced cancers which have not gotten better with regular treatments. The main aims of this study are to check if TAK-188 is safe in adults with advanced or spreading (metastatic) solid tumors, if participants tolerate the treatment with TAK-188 and to learn if TAK-188 works well in adults with certain advanced cancers after their previous treatments didn't work. Participants may receive TAK-188 for up to 1 year. Their health will be monitored after the treatment has ended for up to another year.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participants ≥18 years or ≥ the local legal age of majority, as applicable, at the time of signing the ICF.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Participants must provide biopsy samples (core needle or other surgical procedure) collected within 28 days prior to C1D1 and also on treatment unless procedure is determined to be unsafe following discussion with sponsor. Participants with an archival biopsy specimen collected within 90 days prior to C1D1 of TAK-188 who have not received any other cancer-specific treatment (with the exception of adjuvant endocrine therapy for a history of breast cancer) at least 14 days prior to the biopsy and throughout the period leading up to C1D1 may use that archival specimen in lieu of a new pretreatment biopsy. Archival biopsy from the same tumor must be provided, if available.
Absolute neutrophil count (ANC) ≥1500 per microliter (μL), platelet count ≥75,000/μL, and hemoglobin (Hgb) ≥8.0 g/dL without growth factor support for ANC or transfusion support for platelets within 14 days before the first trial treatment dose. Transfusion of packed red blood cells is allowed, post infusion Hgb must be greater than 8.0 g/dL.
Disqualifiers
Congestive heart failure New York Heart Association Grade III or IV.
Unstable angina, myocardial infarction.
Persistent hypertension ≥160/100 mm mercury (Hg) despite optimal medical therapy.
Ongoing cardiac arrhythmias of Grade >2 (including atrial flutter/fibrillation or intermittent ventricular tachycardia).
Trial design
Design model
Sequential
Treatments tested in this trial
TAK-188
DrugTAK-188 IV infusion
Treatment groups
223 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Group A: Phase 1: TAK-188 Dose EscalationExperimental treatment 1 intervention
Group B: Phase 1b: Backfill CohortExperimental treatment 1 intervention
Group C: Phase 2; Dose Expansion: Cohort AExperimental treatment 1 intervention
Group D: Phase 2; Dose Expansion: Cohort BExperimental treatment 1 intervention
Group E: Phase 2; Dose Expansion: Cohort CExperimental treatment 1 intervention
Group F: Phase 2; Dose Expansion: Cohort DExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Phase 1: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy.
Time frame
From the signing of the informed consent form (ICF) through 90 days after the last dose (Up to approximately 16 months)2
Phase 1: Number of Participants with TEAEs Based on Severity
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. Severity for each TEAE will be determined using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.
Time frame
From the signing of the ICF through 90 days after the last dose (Up to approximately 16 months)3
Phase 1: Number of Participants with Dose- limiting Toxicities (DLTs)
DLTs will be evaluated according to NCI CTCAE, Version 5.0 except cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), will be graded according to American society for transplantation and cellular therapy (ASCST) Consensus Grading for CRS.
Time frame
Up to Cycle 1 (21 days)4
Phase 1: Number of Participants with Treatment-emergent Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event.
Time frame
From the signing of the ICF through 90 days after the last dose (Up to approximately 16 months)Secondary outcomes
1
Phase 1: Recommended Dose for Expansion [RDE(s)] of TAK-188
RDE will be based on the totality of safety, preliminary efficacy, pharmacokinetic (PK), and pharmacodynamic data from phase 1 dose escalation.
Time frame
Up to 12 months2
Phase 1: Cmax: Maximum Observed Plasma Concentration
Time frame
Cycles 1 & 3: Day 1 (pre-dose, end of infusion, 5, 24, 48 & 72 hours post infusion); Days 8 & 15 (pre-dose); Cycles 2 & 4: Day 1 (pre-dose, end of infusion); Cycles 5,7 & 9: Day 1 (pre-dose) & at end of treatment (Cycle length:21 days)3
Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax)
Time frame
Cycles 1 & 3: Day 1 (pre-dose, end of infusion, 5, 24, 48 & 72 hours post infusion); Days 8 & 15 (pre-dose); Cycles 2 & 4: Day 1 (pre-dose, end of infusion); Cycles 5,7 & 9: Day 1 (pre-dose) & at end of treatment (Cycle length:21 days)4
Phase 1: AUC0-last: Area Under The Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration
Time frame
Cycles 1 & 3: Day 1 (pre-dose, end of infusion, 5, 24, 48 & 72 hours post infusion); Days 8 & 15 (pre-dose); Cycles 2 & 4: Day 1 (pre-dose, end of infusion); Cycles 5,7 & 9: Day 1 (pre-dose) & at end of treatment (Cycle length:21 days) Source ClinicalTrials.gov