Squamous Cell Cancer of Head and Neck (SCCHN)Phase 1/2NCT04844073
A Study of TAK-186 (Also Known as MVC-101) in Adults With Advanced or Metastatic Cancer
A Phase 1/2 study testing TAK-186 in people with Squamous Cell Cancer of Head and Neck (SCCHN) and Non-small Cell Lung Cancer (NSCLC), run by Takeda at 27 sites in 4 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Cancer of Head and Neck (SCCHN), Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer
- What is being tested?
- TAK-186
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 27 sitesin 4 countries
- Study dates
- 8 Mar 2021to 17 Jun 2025
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
- Ability to provide informed consent and documentation of informed consent before initiation of any study-related tests or procedures that are not part of standard of care for the participant's disease. Participants must also be willing and able to comply with study procedures, including the acquisition of specified research specimens.
- Life expectancy ≥ 12 weeks
- Measurable disease as per RECIST v1.1 criteria and documented by Computed tomography (CT) and/or magnetic resonance imaging (MRI). The definitions for measurable lesions are the same whether conventional and modified RECIST criteria are applied. Cutaneous or subcutaneous lesions must be measurable by calipers. Lesions to be used as measurable disease for the purpose of response assessment must either a) not reside in a field that has been subjected to prior radiotherapy, or b) have demonstrated clear evidence of radiographic progression since the completion of prior radiotherapy and before study enrollment or c) have been radiated at least 6 months before study enrollment.
- Tumor Histology Types:
- Participants with pathologically proven, unresectable, locally advanced or metastatic solid tumors that based on literature reports are considered to express EGFR. During cohort expansion, participants with locally advanced or metastatic solid tumors expressing EGFR including advanced or metastatic NSCLC, CRC, and HNSCC are eligible for enrollment.
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- Archival Tissue:
- Participants must allow acquisition of existing formalin-fixed paraffin-embedded (FFPE) archival tumor sample, either a block or unstained slides. Participants who provide fresh pretreatment biopsy samples will not be required to submit archival tumor samples.
- Tumor Biopsy:
- Participants must be willing to consent to mandatory pretreatment (during screening) and on-treatment fresh tumor biopsies for cohort expansion phase and backfill in dose escalation. Once the target number of biopsies have been collected, additional paired pretreatment and on-treatment biopsies will not be required; sample collection will be optional after this time point. For fresh tumor biopsies, the lesion must be accessible (those occurring outside the brain or those that are accessible by an interventional or endoscopic procedure) for a low-risk biopsy procedure that does not place the participant at an unjustifiable risk in the opinion of the investigator. Participants who have an archived biopsy specimen available that was obtained up to 90 days prior to treatment initiation and have received no other treatment from the time of biopsy until the start of treatment with TAK-186, may submit that archived specimen in lieu of a pretreatment biopsy upon agreement from the sponsor.
- Laboratory Features:
- Acceptable laboratory parameters as follows:
- Albumin ≥ 3.0 g/dL
- Platelet count ≥ 75 × 103/μL
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count ≥ 1.0 × 103/μL
- Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3.0 × upper limit of normal (ULN); for participants with hepatic metastases, ALT/AST ≤ 5 × ULN
- Total bilirubin ≤ 1.5 × ULN, except participants with Gilbert's syndrome, who may enroll if the conjugated bilirubin is within normal limits.
- Creatinine clearance of ≥ 30 mL/minute using Cockcroft-Gault equation.
- Reproductive Features:
- WOCBP must have a negative serum pregnancy test performed within 72 hours before the initiation of study drug administration. WOCBP must use 1 form of highly effective method and 1 additional effective (barrier) method of contraception at the same time throughout the study, starting at screening through 90 days after the last dose of TAK-186. Contraception methods may be considered highly effective if they can achieve a failure rate of less than 1% per year when used consistently and correctly.
- Male participants with partners of childbearing potential must use barrier contraception during the entire study treatment period through 120 days after the last dose of study drug and must not donate sperm during this period. In addition, male participants should also have their partners use contraception (as documented for female participants) for the same period of time.
- Previous Checkpoint Inhibitor Therapy:
- Participants who have previously received an immune checkpoint before enrollment must have checkpoint inhibitor immune-related toxicity resolved to either Grade ≤ 1 or baseline
- Central nervous system (CNS) metastases must have been treated and meet the following criteria at the time of enrollment:
- Definitive therapy was completed at least 2 weeks prior to the first dose of TAK-186.
- No evidence of radiographic CNS progression following definitive therapy and by the time of study screening.
- Any CNS disease is asymptomatic for at least 7 days (unless symptoms are deemed irreversible by the investigator), the patient is off steroids for at least 7 days, and the patient is either off or on stable doses of anti-epileptic drugs for malignant CNS disease for at least 7 days.
- No concurrent leptomeningeal disease or spinal cord compression.
Who cannot join
- Participants with a history of known autoimmune disease with the exceptions of:
- Vitiligo.
- Psoriasis not requiring systemic treatment for > 1 year before receiving TAK-186.
- History of Graves' disease in participants now euthyroid for > 4 weeks.
- Hypothyroidism managed by thyroid replacement.
- Alopecia.
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- Well-controlled diabetes type 1.
- Major surgery or traumatic injury within 8 weeks before first dose of TAK-186.
- Unhealed wounds from surgery or injury.
- Radiation therapy < 2 weeks before initiation of TAK-186.
- Treatment with > 10 mg per day of prednisone (or equivalent) or other immune-suppressive drugs within the 7 days before the initiation of study drug. Steroids for topical, ophthalmic, inhaled, or nasal administration are allowed.
- Prior therapy within the following timeframe before the planned start of TAK-186 as follows:
- Cytotoxic chemotherapy, small molecule inhibitors, radiation, interventional radiology procedure, or similar investigational therapies: ≤ 2 weeks or 5 half-lives, whichever is shorter.
- Monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or similar investigational therapies: ≤ 4 weeks.
- Concurrent use of hormones either to maintain castrate levels of testosterone in participants with castration-sensitive prostate cancer or for non-cancer-related conditions (e.g., insulin for diabetes, hormone replacement therapy) is acceptable. Bisphosphonates are permitted for supportive care of bone metastases (e.g., breast or prostate cancer) or osteoporosis.
- Clinically significant cardiovascular or vascular disease including:
- Myocardial infarction or unstable angina < 6 months before the initiation of study drug.
- Clinically significant cardiac arrhythmia (e.g., with potential for hemodynamic instability).
- Uncontrolled hypertension: systolic blood pressure > 180 mmHg; diastolic blood pressure > 100 mmHg.
- Pulmonary embolism, requiring treatment occurring < 3 months before initiation of TAK-186.
- QTcF (QT interval by Fridericia correction) prolongation > 480 msec.
- Congestive heart failure (New York Heart Association Class III or IV).
- Pericarditis or clinically significant pericardial effusion.
- Myocarditis. I) Hypotension Grade ≥2.
- Vasculitis not resolved < 6 months before TAK-186 initiation.
- Clinically significant gastrointestinal disorders including:
- Gastrointestinal perforation < 6 months before study drug administration. Participants must have documented evidence (e.g., upper endoscopy, colonoscopy) of completely healed area of prior perforation.
- Gastrointestinal bleeding < 2 months before study drug administration. Participants must have documented evidence (e.g., upper endoscopy, colonoscopy) of completely healed area of prior bleeding.
- Pancreatitis < 6 months before the initiation of study drug. Participants must have a CT scan negative for evidence of remaining disease or normal pancreatic enzyme levels for > 4 weeks before the initiation of TAK-186.
- Diverticulitis flare < 2 months before study drug administration. Participants must have a CT scan negative for evidence of remaining disease before the initiation of TAK-186.
- History of Crohn's disease or ulcerative colitis.
- Inflammatory process that has not resolved for ≥ 4 weeks from the date of first study dose. Participants with any history of Grade 2 or higher noninfectious pneumonitis will be excluded. (Participants with a radiation induced pneumonitis or Grade 1 noninfectious pneumonitis that has resolved may be eligible for enrollment).
- Clinically significant pulmonary compromise (oxygen saturation ≤92% on room air and requirement for any supplemental oxygen at the time of enrollment).
- Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days before the initiation of study drug. Systemic antiviral, antifungal, or antibacterial therapy must be completed > 1 week before the initiation of study drug. Antimicrobial prophylaxis (e.g., for Pneumocystis carinii infection) may continue the antimicrobial for that purpose.
- Vaccination with any live virus vaccine within 4 weeks before the initiation of study drug administration or vaccination with other vaccines 2 weeks before the initiation of study drug administration. Inactivated annual influenza vaccination is allowed.
- Participants who are known to be human immunodeficiency virus positive or who are known to be hepatitis B or C positive. Participants treated for hepatitis C must have viral titers of 0 for ≥ 2 years to be eligible. Participants with hepatitis B having undetectable or ≤ 500 IU hepatitis B viral titers are eligible. Participants with hepatocellular carcinoma (HCC) known history of hepatitis B are excluded, regardless of hepatitis B viral titers.
- Second primary invasive malignancy not in remission for ≥ 3 years. Exceptions include non-melanoma skin cancer, cervical carcinoma in situ, localized prostate cancer (Gleason score ≤ 7), resected melanoma in situ, or any malignancy considered to be indolent and never having required therapy, excluding indolent lymphoid malignancies.
- Any serious underlying medical or psychiatric condition that would preclude understanding and rendering of informed consent or impair the ability of the participant to receive or tolerate the planned treatment.
- Known hypersensitivity to TAK-186 (or any excipient [trehalose, histidine, arginine, or polysorbate-80] contained in the drug or diluent formulation) known hypersensitivity to tocilizumab.
- Investigative site personnel or sponsor personnel directly affiliated with this study or known hypersensitivity to tocilizumab.
- Prisoners or other individuals who are involuntarily detained.
- Any medical or non-medical issue that would contraindicate the participant's participation in the study or confound the results of the study.
- Female participants who are breastfeeding.
Trial locations and contacts
27 sites in 4 countries.
27 sites in 4 countries
United States15 sites
University of Colorado - Anschutz Medical Campus - PPDS
Aurora, Colorado, 80045-2517
Novant Health Cancer Institute - Elizabeth Head and Neck
Charlotte, North Carolina, 28204-3282
Northwestern University
Chicago, Illinois, 60611-2814
Mary Crowley Cancer Research Centers Medical City - SCRI - PPDS
Dallas, Texas, 75230
MD Anderson Cancer Center
Houston, Texas, 77030-4000
Indiana University
Indianapolis, Indiana, 43202
University of Minnesota Medical Center, Fairview
Minneapolis, Minnesota, 55414-2959
Yale University
New Haven, Connecticut, 06510-3206
Columbia University Medical Center -161 Fort Washington
New York, New York, 10032
UC San Diego Moores Cancer Center
San Diego, California, 92037
University of California San Francisco
San Francisco, California, 94143
Fred Hutchinson Cancer Research Center - 1100 Fairview Ave N
Seattle, Washington, 98109
Sanford Cancer Center
Sioux Falls, South Dakota, 57105-1521
Moffitt Cancer Center
Tampa, Florida, 33612
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Australia6 sites
Southern Oncology Clinical Research
Bedford Park, South Australia, 5042
Monash University - Australian Centre for Blood Diseases (ACBD)
Clayton, Victoria, 3168
Avera Cancer Institute at Sioux Falls
Heidelberg, Victoria, 3004
Paula Fox Melanoma and Cancer Centre
Melbourne, Victoria, 3004
Scientia Clinical Research Limited
Randwick, New South Wales, 2031
Chris O'Brien Lifehouse Hospital
Sydney, New South Wales, 2050
South Korea4 sites
Severance Hospital Yonsei University Health System
Seoul, Seodaemun-Gu, 3722
Seoul National University Hospital
Seoul, Seoul Teugbyeolsi, 3080
Asan Medical Center
Seoul, Seoul Teugbyeolsi, 5505
Samsung Medical Center
Seoul, 6351
United Kingdom2 sites
Sarah Cannon Research Institute UK - SCRI - PPDS
London, Middlesex, W1G 6AD
The Christie - PPDS
Manchester, M20 4BX
About this study
Official title: A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of TAK-186 (Also Known as MVC-101), An EGFR x CD3 COnditional Bispecific Redirected Activation (COBRA) Protein in Patients With Unresectable Locally Advanced or Metastatic Cancer
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.
Read the detailed description
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 head and neck squamous cell carcinoma (HNSCC), colorectal cancer (CRC) or non-small cell lung cancer (NSCLC).
- Conditions
- Squamous Cell Cancer of Head and Neck (SCCHN), Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer
- Being tested
- TAK-186
- Keywords
- Unresectable locally advanced cancer, Metastatic cancer, EGFR expressing cancers, EGFR, CD3, CD3-Bispecific, Bispecific, CRC, NSCLC, HNSCC, SCCHN, Squamous head and neck cancer, Lung cancer, Colon cancer
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Neoplasm Metastasis, Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms, Lung Neoplasms, Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAK-186Drug
Also called MVC-101
TAK-186 IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Phase | Experimental | TAK-186 initial 60 minutes infusion and 30 minutes subsequent infusions on Day 1 of every week in Dose Escalation Phase. Participants may receive additional treatment with TAK-186. Dose escalation will be carried out in sequential cohorts of escalating doses. Receives: Drug: TAK-186 |
| Cohort Expansion Phase: NSCLC | Experimental | Participants with NSCLC will be randomized to receive low dose or high dose of RDE of TAK-186 infusion on Day 1 of every week during Dose Expansion Phase of the study. Participants may receive additional treatment with TAK-186. Based on the results for this cohort additional cohorts for HNSCC and CRC, may be enrolled. Receives: Drug: TAK-186 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Non-Cytokine Release Syndrome (CRS) Adverse Events (AEs)
An adverse event (AE) was 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.
Measured: From start of study drug up to 90 days after last dose of the study drug (up to 22 months)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE was 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. TEAE was defined as an AE whose date of onset occurred on or after the first dose of study drug, or an already-present AE that worsened in intensity or frequency following the treatment start, occurring from the first dose of study drug to the day of last dose of study drug. SAE was any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect, or was a medically important event.
Measured: From start of study drug up to 90 days after last dose of the study drug (up to 22 months)
Number of Participants With Cytokine Release Syndrome (CRS) According to American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading
CRS was defined as a systemic inflammatory response caused by the rapid and excessive release of pro-inflammatory cytokines from activated immune cells. Grade 1=temperature greater than or equal to (>=) 38°C; Grade 2= temperature >= 38°C, hypotension not requiring vasopressors, and/or hypoxia requiring low-flow nasal cannula or blow-by oxygen; Grade 3=temperature >= 38°C, hypotension requiring one vasopressor with or without vasopressin, and/or hypoxia requiring high-flow nasal cannula facemask, nonrebreather mask, or venturi mask; Grade 4=temperature >= 38°C, hypotension requiring multiple vasopressors (excluding vasopressin), and/or hypoxia requiring positive pressure (eg, continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP], intubation, and mechanical ventilation). Grade 5= Death due to CRS (if directly attributable). Number of participants with CRS according to ASTCT CRS consensus grading were reported.
Measured: From start of study drug up to 90 days after last dose of the study drug (up to 22 months)
Dose Escalation Phase: Number of Participants With a DLTs
DLTs were evaluated according to national cancer institute common terminology criteria for adverse events (NCI CTCAE) version 5.0. DLT criteria were defined as any of the following events: Hematologic DLTs - Grade 4 neutropenia lasting greater than (>) 5 days; Grade >=3 febrile neutropenia lasting >48 hours or Grade >=3 febrile neutropenia associated with hemodynamic instability or infection; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia and clinically significant bleeding; Grade >=3 hemolysis. Hepatic DLTs - Grade 3 ALT or AST increase; Grade 3 bilirubin increase. Nonhematologic DLTs are Grade >=3 nonhematologic AEs.
Measured: From start of study drug up to Cycle 1 Day 28
Secondary outcomes (13)
Dose Escalation Phase: Recommended Phase 2 Dose (RP2D) of TAK-186
RP2D, the maximum tolerated dose (MTD) of TAK-186 was determined.
Measured: Up to 19 months
Cmax: Maximum Observed Plasma Concentration of TAK-186
Cmax of TAK-186 was reported. As prespecified in the analysis plan, all participants in this combined cohort received the same target dose level of TAK-186. Therefore, data from these participants were pooled and analyzed as a single cohort.
Measured: Cycle 1: Post-dose on Days 1, 8 and 15; Cycle 2: Post-dose Day 1 (Each cycle is 56 days)
Tmax: Time of First Occurrence of Maximum Observed Plasma Concentration (Cmax) of TAK-186
Tmax of TAK-186 was reported. As prespecified in the analysis plan, all participants in this combined cohort received the same target dose level of TAK-186. Therefore, data from these participants were pooled and analyzed as a single cohort.
Measured: Cycle 1: Post-dose on Days 1, 8 and 15; Cycle 2: Post-dose Day 1 (Each cycle is 56 days)
AUCtau: Area Under the Plasma Concentration-time Curve for a Dosing Interval of TAK-186
AUCtau of TAK-186 was reported. As prespecified in the analysis plan, all participants in this combined cohort received the same target dose level of TAK-186. Therefore, data from these participants were pooled and analyzed as a single cohort.
Measured: Cycle 2: Post-dose Day 1 up to pre-dose Day 8 (Each cycle is 56 days)
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for TAK-186
AUClast of TAK-186 was reported. As prespecified in the analysis plan, all participants in this combined cohort received the same target dose level of TAK-186. Therefore, data from these participants were pooled and analyzed as a single cohort.
Measured: Cycle 1: Post-dose on Days 1, 8 and 15; Cycle 2: Post-dose Day 1 (Each cycle is 56 days)
CL: Total Clearance of TAK-186
CL of TAK-186 was reported. As prespecified in the analysis plan, all participants in this combined cohort received the same target dose level of TAK-186. Therefore, data from these participants were pooled and analyzed as a single cohort.
Measured: Cycle 1: Post-dose on Days 1, 8 and 15; Cycle 2: Post-dose Day 1 (Each cycle is 56 days)
Vss: Volume of Distribution at Steady State for TAK-186
Vss of TAK-186 was reported. As prespecified in the analysis plan, all participants in this combined cohort received the same target dose level of TAK-186. Therefore, data from these participants were pooled and analyzed as a single cohort.
Measured: Cycle 1: Post-dose on Days 1, 8 and 15; Cycle 2: Post-dose Day 1 (Each cycle is 56 days)
t1/2: Terminal Half-Life of TAK-186
t1/2 of TAK-186 was reported. As prespecified in the analysis plan, all participants in this combined cohort received the same target dose level of TAK-186. Therefore, data from these participants were pooled and analyzed as a single cohort.
Measured: Cycle 1: Post-dose on Days 1, 8 and 15; Cycle 2: Post-dose Day 1 (Each cycle is 56 days)
Number of Participants With Anti-drug Antibodies (ADA) in Plasma for TAK-186
The number of participants who were negative for TAK-186 ADAs at baseline and became positive in this assay, the number of participants who were negative at baseline and remained negative, and the number of participants who had positive ADAs at baseline and remained positive or became negative were reported.
Measured: From start of study drug up to 30 days after last dose of the study drug (up to 20 months)
Percentage of Participants With Objective Response (OR)
Objective response rate (ORR) was defined as the percentage of participants who achieved confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Confirmed responses were those that persisted on repeat imaging assessments at least 4 weeks after initial documentation of response. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 millimeters (mm). PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From start of study drug up to end of study (up to 22 months)
Duration of Response (DOR)
The DOR was assessed according to RECIST version 1.1. It was defined as time in from initial confirmed objective response (CR or PR) to the time of documented PD or death from any cause, whichever occurs first. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From start of study drug up to end of study (up to 22 months)
Progression-free Survival (PFS)
PFS was measured from the date of first dose to first occurrence of objective PD using both RECIST v1.1, or the date of death from any cause. PD: 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). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: From start of study drug up to end of study (up to 22 months)
Overall Survival (OS)
OS was measured from the time from the first dose of study drug until the date of death due to any cause.
Measured: From start of study drug up to end of study (up to 22 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2021
- Study start8 Mar 2021
- Primary completion17 Jun 2025
- Study completion17 Jun 2025
Why it stopped: Sponsor decision based on limited anti-cancer activity of TAK-186.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Squamous Cell Cancer of Head and Neck (SCCHN)Studies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04844073
- Sponsor's protocol ID
- CP-MVC-101-01
- Status last verified
- Aug 2026
- First submitted
- 30 Mar 2021
- Last updated
- 24 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of TAK-186 (Also Known as MVC-101), An EGFR x CD3 COnditional Bispecific Redirected Activation (COBRA) Protein in Patients With Unresectable Locally Advanced or Metastatic Cancer
- ClinicalTrials.gov ID
- NCT04844073
- Acronym / sponsor ID
- CP-MVC-101-01
- Conditions
- Squamous Cell Cancer of Head and Neck (SCCHN), Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer
- Keywords
- Unresectable locally advanced cancer, Metastatic cancer, EGFR expressing cancers, EGFR, CD3, CD3-Bispecific, Bispecific, CRC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision based on limited anti-cancer activity of TAK-186.
- Enrolment
- 95 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 8 Mar 2021 (actual)
- Primary completion
- 17 Jun 2025 (actual)
- Study completion
- 17 Jun 2025 (actual)
- First posted
- 14 Apr 2021 (actual)
- Results
- Posted 24 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 head and neck squamous cell carcinoma (HNSCC), colorectal cancer (CRC) or non-small cell lung cancer (NSCLC).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Phase | Experimental | Drug: TAK-186TAK-186 initial 60 minutes infusion and 30 minutes subsequent infusions on Day 1 of every week in Dose Escalation Phase. Participants may receive additional treatment with TAK-186. Dose escalation will be carried out in sequential cohorts of escalating doses. |
| Cohort Expansion Phase: NSCLC | Experimental | Drug: TAK-186Participants with NSCLC will be randomized to receive low dose or high dose of RDE of TAK-186 infusion on Day 1 of every week during Dose Expansion Phase of the study. Participants may receive additional treatment with TAK-186. Based on the results for this cohort additional cohorts for HNSCC and CRC, may be enrolled. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
- Ability to provide informed consent and documentation of informed consent before initiation of any study-related tests or procedures that are not part of standard of care for the participant's disease. Participants must also be willing and able to comply with study procedures, including the acquisition of specified research specimens.
- Life expectancy ≥ 12 weeks
- Measurable disease as per RECIST v1.1 criteria and documented by Computed tomography (CT) and/or magnetic resonance imaging (MRI). The definitions for measurable lesions are the same whether conventional and modified RECIST criteria are applied. Cutaneous or subcutaneous lesions must be measurable by calipers. Lesions to be used as measurable disease for the purpose of response assessment must either a) not reside in a field that has been subjected to prior radiotherapy, or b) have demonstrated clear evidence of radiographic progression since the completion of prior radiotherapy and before study enrollment or c) have been radiated at least 6 months before study enrollment.
- Participants with pathologically proven, unresectable, locally advanced or metastatic solid tumors that based on literature reports are considered to express EGFR. During cohort expansion, participants with locally advanced or metastatic solid tumors expressing EGFR including advanced or metastatic NSCLC, CRC, and HNSCC are eligible for enrollment.
Key exclusion criteria (43 listed)
- Participants with a history of known autoimmune disease with the exceptions of:
- Major surgery or traumatic injury within 8 weeks before first dose of TAK-186.
- Unhealed wounds from surgery or injury.
- Radiation therapy < 2 weeks before initiation of TAK-186.
- Treatment with > 10 mg per day of prednisone (or equivalent) or other immune-suppressive drugs within the 7 days before the initiation of study drug. Steroids for topical, ophthalmic, inhaled, or nasal administration are allowed.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAK-186Also: MVC-101TAK-186 IV infusion. | Drug | Cohort Expansion Phase: NSCLC, Dose Escalation Phase |
Primary outcome
Number of Participants With Non-Cytokine Release Syndrome (CRS) Adverse Events (AEs)
Time frame: From start of study drug up to 90 days after last dose of the study drug (up to 22 months)
An adverse event (AE) was 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From start of study drug up to 90 days after last dose of the study drug (up to 22 months)
An AE was 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. TEAE was defined as an AE whose date of onset occurred on or after the first dose of study drug, or an already-present AE that worsened in intensity or frequency following the treatment start, occurring from the first dose of study drug to the day of last dose of study drug. SAE was any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect, or was a medically important event.
Number of Participants With Cytokine Release Syndrome (CRS) According to American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading
Time frame: From start of study drug up to 90 days after last dose of the study drug (up to 22 months)
CRS was defined as a systemic inflammatory response caused by the rapid and excessive release of pro-inflammatory cytokines from activated immune cells. Grade 1=temperature greater than or equal to (>=) 38°C; Grade 2= temperature >= 38°C, hypotension not requiring vasopressors, and/or hypoxia requiring low-flow nasal cannula or blow-by oxygen; Grade 3=temperature >= 38°C, hypotension requiring one vasopressor with or without vasopressin, and/or hypoxia requiring high-flow nasal cannula facemask, nonrebreather mask, or venturi mask; Grade 4=temperature >= 38°C, hypotension requiring multiple vasopressors (excluding vasopressin), and/or hypoxia requiring positive pressure (eg, continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP], intubation, and mechanical ventilation). Grade 5= Death due to CRS (if directly attributable). Number of participants with CRS according to ASTCT CRS consensus grading were reported.
Dose Escalation Phase: Number of Participants With a DLTs
Time frame: From start of study drug up to Cycle 1 Day 28
DLTs were evaluated according to national cancer institute common terminology criteria for adverse events (NCI CTCAE) version 5.0. DLT criteria were defined as any of the following events: Hematologic DLTs - Grade 4 neutropenia lasting greater than (>) 5 days; Grade >=3 febrile neutropenia lasting >48 hours or Grade >=3 febrile neutropenia associated with hemodynamic instability or infection; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia and clinically significant bleeding; Grade >=3 hemolysis. Hepatic DLTs - Grade 3 ALT or AST increase; Grade 3 bilirubin increase. Nonhematologic DLTs are Grade >=3 nonhematologic AEs.
13 secondary outcomes
Dose Escalation Phase: Recommended Phase 2 Dose (RP2D) of TAK-186
Time frame: Up to 19 months
Cmax: Maximum Observed Plasma Concentration of TAK-186
Time frame: Cycle 1: Post-dose on Days 1, 8 and 15; Cycle 2: Post-dose Day 1 (Each cycle is 56 days)
Tmax: Time of First Occurrence of Maximum Observed Plasma Concentration (Cmax) of TAK-186
Time frame: Cycle 1: Post-dose on Days 1, 8 and 15; Cycle 2: Post-dose Day 1 (Each cycle is 56 days)
AUCtau: Area Under the Plasma Concentration-time Curve for a Dosing Interval of TAK-186
Time frame: Cycle 2: Post-dose Day 1 up to pre-dose Day 8 (Each cycle is 56 days)
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for TAK-186
Time frame: Cycle 1: Post-dose on Days 1, 8 and 15; Cycle 2: Post-dose Day 1 (Each cycle is 56 days)
CL: Total Clearance of TAK-186
Time frame: Cycle 1: Post-dose on Days 1, 8 and 15; Cycle 2: Post-dose Day 1 (Each cycle is 56 days)
Vss: Volume of Distribution at Steady State for TAK-186
Time frame: Cycle 1: Post-dose on Days 1, 8 and 15; Cycle 2: Post-dose Day 1 (Each cycle is 56 days)
t1/2: Terminal Half-Life of TAK-186
Time frame: Cycle 1: Post-dose on Days 1, 8 and 15; Cycle 2: Post-dose Day 1 (Each cycle is 56 days)
Number of Participants With Anti-drug Antibodies (ADA) in Plasma for TAK-186
Time frame: From start of study drug up to 30 days after last dose of the study drug (up to 20 months)
Percentage of Participants With Objective Response (OR)
Time frame: From start of study drug up to end of study (up to 22 months)
Duration of Response (DOR)
Time frame: From start of study drug up to end of study (up to 22 months)
Progression-free Survival (PFS)
Time frame: From start of study drug up to end of study (up to 22 months)
Overall Survival (OS)
Time frame: From start of study drug up to end of study (up to 22 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
27 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TAK-186 in people with Squamous Cell Cancer of Head and Neck (SCCHN) and Non-small Cell Lung Cancer (NSCLC), run by Takeda at 27 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Australia, South Korea, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Non-Cytokine Release Syndrome (CRS) Adverse Events (AEs) (time frame: From start of study drug up to 90 days after last dose of the study drug (up to 22 months)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.