An Open-label, Dose Escalation and Expansion, Phase 1/2 Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of TAK- 188, an Anti-CCR8 Antibody-Drug- Conjugate, as a Single Agent in Adult Participants With Locally Advanced or Metastatic Solid Tumors
Summary
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.
Arms & interventions
- DrugTAK-188
TAK-188 IV infusion
Outcome measures
Primary
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)
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)
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)
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)
Phase 1: Number of Participants with Treatment-emergent Adverse Events Leading to Dose Modifications and Treatment Discontinuations
Time frame: From the signing of the ICF through 90 days after the last dose (Up to approximately 16 months)
Phase 2: Overall Response Rate (ORR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
ORR is defined as the percentage of participants who achieve Complete Response (CR) and Partial Response (PR) (determined by the investigator) during the study according to RECIST Version 1.1. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease by 30% and no new sites of disease. Stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Time frame: Up to 24 months
Phase 2: Disease Control Rate (DCR)
DCR is defined as the percentage of participants who achieve SD or better (CR+PR+SD determined by the investigator) equal to or more than (≥) 6 weeks during the study.
Time frame: Up to 24 months
Phase 2: Duration of Response (DOR)
DOR is defined as the time from the date of first documentation of a confirmed partial response (cPR) or better to the date of first documentation of PD or death for responders (cPR or better).
Time frame: Up to 24 months
Secondary
Phase 1: Recommended Dose for Expansion [RDE(s)] of TAK-188
Time frame: Up to 12 months
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)
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)
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)
Phase 1: AUC0-inf: Area Under The Plasma Concentration-Time Curve From Time 0 to Infinity
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)
Phase 1: t1/2z: Terminal Disposition Phase Half-life
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)
Phase 1: CL: Total Clearance After Intravenous Administration
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)
Phase 1: Vss: Volume of Distribution at Steady State After Intravenous Administration
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)
Phase 1: ORR
Time frame: Up to 24 months
Phases 1: Disease Control Rate (DCR)
Time frame: Up to 24 months
Phases 1: Duration of Response (DOR)
Time frame: Up to 24 months
Phase 1: Time to Response (TTR)
Time frame: Up to 24 months
Phase 1 and 2: Change from Baseline in Regulatory T Cell (Treg) Abundance Within the Tumor Microenvironment (TME)
Time frame: Baseline, Cycle 2 Day 10 (Cycle length: 21 Days)
Phase 1 and 2: Change from Baseline in Effector T Cell (Teff) Abundance Within the TME
Time frame: Baseline, Cycle 2 Day 10 (Cycle length: 21 Days)
Phase 1 and 2: Percentage of Participants Who Develop Anti-TAK-188 Antibodies
Time frame: Cycles 1 Through 9 Day 1, and at End of Treatment (up to approximately 13 months)]
Phase 2: Time to Response (TTR)
Time frame: Up to 24 months
Phase 2: Progression-free Survival (PFS)
Time frame: Up to 24 months
Phase 2: Overall Survival (OS)
Time frame: Up to 24 months
Phase 2: Cmax: Maximum Observed Plasma Concentration for TAK-188
Time frame: Cycles 1 through 4: Days 1 and 8 (pre-dose and end of infusion); Cycles 5, 7, and 9: Day 1 (pre-dose) & at end of treatment (Cycle length: 21 Days)
Phase 2: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-188
Time frame: Cycles 1 through 4: Days 1 and 8 (pre-dose and end of infusion); Cycles 5, 7, and 9: Day 1 (pre-dose) & at end of treatment (Cycle length: 21 Days)
Phase 2: AUC0-last: Area Under The Concentration-Time Curve From Time 0 to Time of The Last Quantifiable Concentration
Time frame: Cycles 1 through 4: Days 1 and 8 (pre-dose and end of infusion); Cycles 5, 7, and 9: Day 1 (pre-dose) & at end of treatment (Cycle length: 21 Days)
Phase 2: AUC0-inf: Area Under The Plasma Concentration-Time Curve From Time 0 to Infinity
Time frame: Cycles 1 through 4: Days 1 and 8 (pre-dose and end of infusion); Cycles 5, 7, and 9: Day 1 (pre-dose) & at end of treatment (Cycle length: 21 Days)
Phase 2: t1/2z: Terminal Disposition Phase Half-life for for TAK-188
Time frame: Cycles 1 through 4: Days 1 and 8 (pre-dose and end of infusion); Cycles 5, 7, and 9: Day 1 (pre-dose) & at end of treatment (Cycle length: 21 Days)
Phase 2: CL: Total Clearance After Intravenous Administration for TAK-188
Time frame: Cycles 1 through 4: Days 1 and 8 (pre-dose and end of infusion); Cycles 5, 7, and 9: Day 1 (pre-dose) & at end of treatment (Cycle length: 21 Days)
Phase 2: Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-188
Time frame: Cycles 1 through 4: Days 1 and 8 (pre-dose and end of infusion); Cycles 5, 7, and 9: Day 1 (pre-dose) & at end of treatment (Cycle length: 21 Days)
Eligibility criteria
Study locations (15)
UCLA Health-Santa Monica Cancer Care (Cancer Care - Santa Monica)
Santa Monica, California, 90404
Yale School of Medicine - Smilow Cancer Hospital - Center for Thoracic Cancers
New Haven, Connecticut, 06511
Florida Cancer Specialists - Lake Nona
Orlando, Florida, 32827
Johns Hopkins
Baltimore, Maryland, 21231
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
START Midwest
Grand Rapids, Michigan, 49546
Washington University
St Louis, Missouri, 63108
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106-1716
Providence Cancer Institute, Franz Clinic
Portland, Oregon, 97213-2933
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497
SCRI Oncology
Nashville, Tennessee, 37203
MD Anderson Cancer Center
Houston, Texas, 77030-4000
NEXT Dallas
Irving, Texas, 75039
START San Antonio
San Antonio, Texas, 78229
NEXT Virginia
Fairfax, Virginia, 22031