A Study of TAK-186 (Also Known as MVC-101) in Adults With Advanced or Metastatic Cancer

NCT04844073 | Terminated Phase 1 FDA Drug

• 1 other identifier: CP-MVC-101-01
• Study Type: interventional
• Target: 95
• Locations: 4 countries
• Sites: 27

Brief 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). 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.

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; NSCLC; HNSCC; SCCHN; Squamous head and neck cancer; Lung cancer; Colon cancer

Outcome Measures

Primary Outcomes (3)

• 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.

  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).

  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)

  DLT Evaluation Period (up to Day 28) in Dose Escalation Phase

Secondary Outcomes (16)

• Recommended Phase 2 Dose (RP2D)

  Up to approximately 13 months

• Cmax: Maximum Observed Plasma Concentration of TAK-186

  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

  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

  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

  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)

Study Arms (2)

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.

Drug: TAK-186

Cohort Expansion Phase: NSCLC

EXPERIMENTAL

Participants with non-small cell lung cancer (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.

Drug: TAK-186

Interventions

TAK-186 DRUG

TAK-186 IV infusion.

Also known as: MVC-101

Cohort Expansion Phase: NSCLC; Dose Escalation Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 Response Evaluation Criteria in Solid Tumors (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.
• \* Tumors During Cohort Expansion:
• Participants with pathologically proven, unresectable, locally advanced or metastatic solid tumors that based on literature reports are considered to express EGFR are eligible for enrollment:
• NSCLC: locally advanced or metastatic NSCLC that has progressed during or following treatment with platinum-based chemotherapy, a checkpoint inhibitor (unless known to be PD-L1 negative), or targeted therapy (for participants with a known actionable mutation).
• CRC: locally advanced or metastatic CRC that has progressed after systemic therapies, including irinotecan, oxaliplatin, an anti-EGFR inhibitor (if K-RAS or N-RAS is WT), a checkpoint inhibitor (if MSI-H), and a VEGF inhibitor (if locally approved and accessible as a standard-of-care).
• HNSCC: HNSCC that has progressed during or following treatment with a checkpoint inhibitor (unless ineligible, e.g, PD-L1 negative) and platinum-based chemotherapy (unless ineligible for or intolerant to platinum-based chemotherapy) with or without cetuximab for metastatic or recurrent disease.
• Participants with salivary gland tumors will not be considered as having HNSCC.
• Participants who refuse surgery for potentially curable disease where the surgery or radiotherapy could result in severe morbidity are eligible. The reason for the refusal will be captured in the electronic case report form (eCRFs).
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (27)

UC San Diego Moores Cancer Center

San Diego, California, 92037, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado - Anschutz Medical Campus - PPDS

Aurora, Colorado, 80045-2517, United States

Location

Yale University

New Haven, Connecticut, 06510-3206, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northwestern University

Chicago, Illinois, 60611-2814, United States

Location

Indiana University

Indianapolis, Indiana, 43202, United States

Location

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, 55414-2959, United States

Location

Columbia University Medical Center -161 Fort Washington

New York, New York, 10032, United States

Location

Novant Health Cancer Institute - Elizabeth Head and Neck

Charlotte, North Carolina, 28204-3282, United States

Location

Sanford Cancer Center

Sioux Falls, South Dakota, 57105-1521, United States

Location

Mary Crowley Cancer Research Centers Medical City - SCRI - PPDS

Dallas, Texas, 75230, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030-4000, United States

Location

Fred Hutchinson Cancer Research Center - 1100 Fairview Ave N

Seattle, Washington, 98109, United States

Location

Scientia Clinical Research Limited

Randwick, New South Wales, 2031, Australia

Location

Chris O'Brien Lifehouse Hospital

Sydney, New South Wales, 2050, Australia

Location

Southern Oncology Clinical Research

Bedford Park, South Australia, 5042, Australia

Location

Monash University - Australian Centre for Blood Diseases (ACBD)

Clayton, Victoria, 3168, Australia

Location

Avera Cancer Institute at Sioux Falls

Heidelberg, Victoria, 3004, Australia

Location

Paula Fox Melanoma and Cancer Centre

Melbourne, Victoria, 3004, Australia

Location

Severance Hospital Yonsei University Health System

Seoul, Seodaemun-Gu, 3722, South Korea

Location

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi, 3080, South Korea

Location

Asan Medical Center

Seoul, Seoul Teugbyeolsi, 5505, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

Sarah Cannon Research Institute UK - SCRI - PPDS

London, Middlesex, W1G 6AD, United Kingdom

Location

The Christie - PPDS

Manchester, M20 4BX, United Kingdom

Location

Related Links

• 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.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Neoplasm Metastasis; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Lung Neoplasms; Colonic Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2021
• First Posted: April 14, 2021
• Study Start: March 8, 2021
• Primary Completion: June 17, 2025
• Study Completion: June 17, 2025
• Last Updated: December 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (15); KR (4); AU (6); GB (2)