The main aim of this study is to check for side effects and tolerability of TAK-186 (also known as MVC-101) in adults with unremovable advanced or metastatic cancer. Another aim is to characterize and evaluate the activity of TAK-186 (MVC-101). Participants may receive treatment throughout the study for a maximum of 13 months and will be followed up at 30 days and 90 days and then every 12 weeks for up to 48 weeks after the last treatment.
This Phase 1/2, open-label study will characterize safety and dose-limiting toxicities (DLTs) of TAK-186. Dose escalation will occur in participants with advanced solid tumors. A Cohort Expansion Phase will be enrolled to further characterize safety and initial anti-tumor activity in participants with solid tumors expressing epidermal growth factor receptor (EGFR), including HNSCC, CRC or NSCLC.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
95
TAK-186 IV infusion.
Number of Participants with Treatment Emergent Adverse Events (TEAEs)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. All non immune-related AEs with start date from first dose of study drug until 30 days after the last dose of study drug will be considered as TEAEs. All immune-related AEs with start date from first dose of study drug until 90 days after the last dose of study drug will be considered as TEAEs. AEs will be reported based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.
Time frame: From the signing of ICF through 30 days after the last dose of study drug for non immune-related AEs, and through 90 days after the last dose of study drug for immune-related AEs (Up to approximately 13 months)
Number of Participants with Cytokine Release Syndrome/Infusion Reactions
Number of participants with infusion reactions as per American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria will be reported. Grade 1 - Mild (Symptomatic Management): Fever ≥38\^o C, No hypotension, No hypoxia, Grade 2 - Moderate (Moderate Intervention): Fever ≥38\^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula or blow-by oxygen, Grade 3 - Severe (Aggressive Intervention): Fever ≥ 38\^ o C , Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula, facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening (Life-sustaining intervention): Fever ≥38\^oC, Hypotension requiring multiple vasopressors (excluding vasopressin), Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation and mechanical ventilation).
Time frame: From the signing of ICF through 30 days after the last dose of study drug (Up to approximately 13 months)
Number of Participants with a Dose-Limiting Toxicity (DLT)
Time frame: DLT Evaluation Period (up to Day 28) in Dose Escalation Phase
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UC San Diego Moores Cancer Center
San Diego, California, United States
University of California San Francisco
San Francisco, California, United States
University of Colorado - Anschutz Medical Campus - PPDS
Aurora, Colorado, United States
Yale University
New Haven, Connecticut, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, United States
Moffitt Cancer Center
Tampa, Florida, United States
Northwestern University
Chicago, Illinois, United States
Indiana University
Indianapolis, Indiana, United States
University of Minnesota Medical Center, Fairview
Minneapolis, Minnesota, United States
Columbia University Medical Center -161 Fort Washington
New York, New York, United States
...and 17 more locations
Recommended Phase 2 Dose (RP2D)
Time frame: Up to approximately 13 months
Cmax: Maximum Observed Plasma Concentration of TAK-186
Time frame: Pre-dose and at multiple time points post-dose on Days 1, 2, 8, 9, 10, 15, 22, 29, 36, 43, 50 up to end of treatment (Up to 13 months)
Tmax: Time of First Occurrence of Maximum Observed Plasma Concentration (Cmax) of TAK-186
Time frame: Pre-dose and at multiple time points post-dose on Days 1, 2, 8, 9, 10, 15, 22, 29, 36, 43, 50 up to end of treatment (Up to 13 months)
AUCtau: Area Under the Plasma Concentration-time Curve for a Dosing Interval for TAK-186
Time frame: Pre-dose and at multiple time points post-dose on Days 1, 2, 8, 9, 10, 15, 22, 29, 36, 43, 50 up to end of treatment (Up to 13 months)
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for TAK-186
Time frame: Pre-dose and at multiple time points post-dose on Days 1, 2, 8, 9, 10, 15, 22, 29, 36, 43, 50 up to end of treatment (Up to 13 months)
AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-186
Time frame: Pre-dose and at multiple time points post-dose on Days 1, 2, 8, 9, 10, 15, 22, 29, 36, 43, 50 up to end of treatment (Up to 13 months)
Ctrough: Trough Plasma Concentration of TAK-186
Time frame: Pre-dose and at multiple time points post-dose on Days 1, 2, 8, 9, 10, 15, 22, 29, 36, 43, 50 up to end of treatment (Up to 13 months)
CL: Clearance of TAK-186
Time frame: Pre-dose and at multiple time points post-dose on Days 1, 2, 8, 9, 10, 15, 22, 29, 36, 43, 50 up to end of treatment (Up to 13 months)
Vss: Volume of Distribution at Steady State for TAK-186
Time frame: Pre-dose and at multiple time points post-dose on Days 1, 2, 8, 9, 10, 15, 22, 29, 36, 43, 50 up to end of treatment (Up to 13 months)
t1/2: Terminal Half-Life of TAK-186
Time frame: Pre-dose and at multiple time points post-dose on Days 1, 2, 8, 9, 10, 15, 22, 29, 36, 43, 50 up to end of treatment (Up to 13 months)
Number of Participants with Anti-drug Antibodies (ADA) in Plasma for TAK-186
Time frame: Up to approximately 13 months
Preliminary Anti-tumor Activity of TAK-186 in Participants with Advanced Cancer Based on Tumor Protein Marker Changes in Serum
Time frame: Up to approximately 13 months
Objective Response Rate (ORR)
ORR will be calculated based on the percentage of participants achieving Complete Response \[CR\] or Partial Response \[PR\] as per RECIST v1.1 (both confirmed and unconfirmed) and modified RECIST v1.1.
Time frame: Up to approximately 13 months
Duration of Response
Duration of response will be calculated for responders as the time from initial confirmed objective response (CR or PR) to the time of documented Progressive Disease (PD) using both RECIST v1.1 and modified RECIST v1.1 or death from any cause, whichever occurs first.
Time frame: Up to approximately 13 months
Progression-free Survival (PFS)
PFS will be calculated as the time from the date of the first dose of study drug to the date of any documented confirmed PD using both RECIST v1.1 and modified RECIST v1.1 or the date of death from any cause, whichever occurs first.
Time frame: Up to approximately 13 months
Overall Survival (OS)
OS will be calculated as the time from the first dose of study drug until the date of death due to any cause.
Time frame: Up to approximately 13 months