A Study of TAK-788 in Adults With Non-Small Cell Lung Cancer

NCT02716116 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: AP32788-15-101U1111-1217-72052016-001271-68
• Study Type: interventional
• Target: 334
• Locations: 10 countries
• Sites: 62

Brief Summary

This study is about a medicine called TAK-788, also known as mobocertinib, given to adults with non-small cell lung cancer. The main aims of this study are to check if there are any side effects from TAK-788, to learn how TAK-788 is processed by the body, and to determine the best dose of TAK-788 to treat this condition. Participants will take TAK-788 capsules with chemotherapy. Participants will continue to take TAK-788 unless they or their doctor decide they should stop this treatment. Participants will take TAK-788 capsules with or without chemotherapy under antidiarrhea prevention to determine the safety of TAK-788 treatment. Non-Asian, non-White participants will take TAK-788 to determine the safety and tolerability of TAK-788 treatment.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (5)

• Part 1, Dose Escalation Component: Recommended Phase 2 Dose (RP2D) of Orally Administered TAK-788

  Cycle 1 (Cycle length is equal to [=] 28 days)

• Part 2, Expansion Cohorts 1, 2, 4, 5 and 7: Confirmed Objective Response Rate (ORR) Assessed by the Investigator

  Up to 36 months after first dose

• Part 2, Expansion Cohort 3: Intracranial ORR (iORR) Assessed by Independent Review Committee (IRC)

  Up to 36 months after first dose

• Part 2, Expansion Cohort 6: Confirmed ORR Assessed by IRC

  Up to 36 months after first dose

• Part 3, Extension Cohort: Confirmed ORR Assessed by IRC

  Up to 36 months after first dose

Secondary Outcomes (22)

• Part 1, Dose Escalation Component: Dose Limiting Toxicities (DLTs) of TAK-788

  Cycle 1 (Cycle length=28 days)

• Part 1, Dose Escalation Component: Maximum Tolerated Dose (MTD) of TAK-788

  Cycle 1 (Cycle length=28 days)

• Parts 1 and 2, Dose Escalation and Expansion Cohorts: Cmax; Maximum Observed Concentration of TAK-788 and its Metabolites

  Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2)

• Parts 1 and 2, Dose Escalation and Expansion Cohorts: Tmax; Time of First Occurrence of Maximum Plasma Concentration (Cmax) of TAK-788 and its Metabolites

  Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2)

• Parts 1 and 2, Dose Escalation and Expansion Cohorts: AUC 24; Area Under the Concentration-time Curve from Time Zero to 24 hours for TAK-788 and its Metabolites

  Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2)

Study Arms (9)

Part 1: Dose Escalation Component

EXPERIMENTAL

TAK-788 treatment for participants with advanced NSCLC.

Drug: TAK-788

Part 2: Expansion Cohort 1

EXPERIMENTAL

TAK-788 treatment for NSCLC participants with EGFR exon 20 activating insertions, who have either not received or not shown an objective response to an EGFR tyrosine kinase inhibitors (TKI), and who have no active, measurable central nervous system (CNS) metastases.

Drug: TAK-788

Part 2: Expansion Cohort 2

EXPERIMENTAL

TAK-788 treatment for NSCLC participants with HER2 exon 20 activating insertions or point mutations and no active, measurable CNS metastases.

Drug: TAK-788

Part 2: Expansion Cohort 3

EXPERIMENTAL

TAK-788 treatment for NSCLC participants with EGFR exon 20 activating insertions or HER2 exon 20 activating insertions or point mutations and active, measurable CNS metastases.

Drug: TAK-788

Part 2: Expansion Cohort 4

EXPERIMENTAL

TAK-788 treatment for NSCLC participants with other targets against which TAK-788 is active (examples include EGFR exon 19 deletions or exon 21 substitutions \[with or without T790M mutations\] and other uncommon EGFR activating mutations), without active CNS metastases.

Drug: TAK-788

Part 2: Expansion Cohort 5

EXPERIMENTAL

TAK-788 treatment for NSCLC participants with EGFR exon 20 activating insertions, who have previously shown an objective response to an EGFR TKI and subsequently progressed without active CNS metastases.

Drug: TAK-788

Part 2: Expansion Cohort 6

EXPERIMENTAL

TAK-788 treatment NSCLC participants with EGFR exon 20 activating insertions, who have not received prior systemic anticancer treatment for locally advanced or metastatic disease without active CNS metastases

Drug: TAK-788

Part 2: Expansion Cohort 7

EXPERIMENTAL

TAK-788 treatment for participants with solid tumors other than NSCLC with EGFR/HER2 mutations against which TAK-788 is active without active CNS metastases.

Drug: TAK-788

Part 3: Extension Cohort

EXPERIMENTAL

TAK-788 treatment for participants with previously treated locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations.

Drug: TAK-788

Interventions

TAK-788 DRUG

TAK-788 capsules.

Also known as: AP32788

Part 1: Dose Escalation Component; Part 2: Expansion Cohort 1; Part 2: Expansion Cohort 2; Part 2: Expansion Cohort 3; Part 2: Expansion Cohort 4; Part 2: Expansion Cohort 5; Part 2: Expansion Cohort 6; Part 2: Expansion Cohort 7; Part 3: Extension Cohort

Eligibility Criteria

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

You may qualify if:

• Have histologically or cytologically confirmed locally advanced (and not a candidate for definitive therapy) or metastatic NSCLC disease (Stage IIIB or IV) or other solid tumors. For all cohorts except Expansion Cohort 7, the locally advanced or metastatic disease is NSCLC. For Expansion Cohort 7, the locally advanced or metastatic disease is any solid tumor other than NSCLC.
• Must have sufficient tumor tissue available for analysis.
• Must have measurable disease by response evaluation criteria in solid tumors (RECIST) v1.1.
• Male or female adult participants (aged 18 years or older, or as defined per local regulations).
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
• Minimum life expectancy of 3 months or more.
• Adequate organ function at baseline.
• Normal QT interval on screening electrocardiogram (ECG), defined as QT interval corrected (Fridericia) (QTcF) of less than or equal to (≤ ) 450 millisecond (ms) in males or ≤ 470 ms in females.
• Willingness and ability to comply with scheduled visits and study procedures.
• \. Refractory to standard available therapies.
• Have a documented EGFR in-frame exon 20 insertion by a local test.
• Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
• Prior treatment with an EGFR TKI is allowed unless the participants had an objective response and subsequent progression as assessed by the investigator or treating physician.
• Have one of the following documented by a local test:
• A HER2 exon 20 insertion;

You may not qualify if:

• Previously received TAK-788.
• Received small-molecule anticancer therapy (including cytotoxic chemotherapy, and investigational agents, ≤ 14 days prior to first dose of TAK-788 (except for reversible EGFR TKIs \[that is, erlotinib or gefitinib\], which are allowed in the dose escalation and expansion cohorts up to 7 days prior to the first dose of TAK-788).
• Received antineoplastic monoclonal antibodies including immunotherapy within 28 days of the first dose of TAK-788.
• Have been diagnosed with another primary malignancy other than NSCLC except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or participants with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
• Received radiotherapy \<=14 days prior to the first dose of TAK-788 or has not recovered from radiotherapy-related toxicities. Palliative radiation administered outside the chest and brain, stereotactic radiosurgery (SRS), and stereotactic body radiotherapy are allowed up to 7 days prior to the first dose
• Received a moderate or strong CYP4503A inhibitor or moderate or strong CYP3A inducer within 10 days prior to first dose of TAK-788.
• Have undergone major surgery within 28 days prior to first dose of TAK-788. Minor surgical procedures, such as catheter placement or minimally invasive biopsy, are allowed.
• Part 1 (dose escalation) and Expansion Cohorts 1 to 3 of Part 2 (expansion phase) only:
• Have symptomatic CNS metastases at screening or asymptomatic disease requiring corticosteroids to control symptoms within 7 days prior to the first dose of TAK-788.
• Part 3 (extension cohort) and Expansion Cohorts 4 to 7 of Part 2 (expansion phase) only:
• Have known active brain metastases (have either previously untreated intracranial CNS metastases or previously treated intracranial CNS metastases with radiologically documented new or progressing CNS lesions). Brain metastases are allowed if they have been treated with surgery and/or radiation and have been stable without requiring corticosteroids to control symptoms within 7 days before the first dose of TAK-788, and have no evidence of new or enlarging brain metastases.
• Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic).
• Have significant, uncontrolled, or active cardiovascular disease.
• Have a known history of uncontrolled hypertension. Participants with hypertension should be under treatment on study entry to control blood pressure.
• Have prolonged QTcF interval, or being treated with medications known to be associated with the development of torsades de pointes.

Sponsors & Collaborators

• Takeda: lead

Study Sites (62)

Brookwood Medical Center

Birmingham, Alabama, 35209, United States

Location

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

The Oncology Institute of Hope and Innovation - West Tucson

Tucson, Arizona, 85745, United States

Location

City of Hope Comprehensive Cancer Center - Duarte

Duarte, California, 91010, United States

Location

Compassionate Cancer Care - Fountain Valley

Fountain Valley, California, 92708, United States

Location

University of California San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Pacific Shores Medical Group-Long Beach Elm

Long Beach, California, 90813, United States

Location

Cancer and Blood Specialty Clinic

Los Alamitos, California, 90720, United States

Location

University of California Irvine Health Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Stanford Cancer Center - Palo Alto

Palo Alto, California, 94305, United States

Location

SLO Oncology and Hematology Health Center

San Luis Obispo, California, 93405, United States

Location

The Oncology Institute of Hope and Innovation

Whittier, California, 90603, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

AdventHealth Orlando

Orlando, Florida, 32804, United States

Location

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

The University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Investigative Clinical Research - Indiana

Indianapolis, Indiana, 46260, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Siteman Cancer Center - Washington University Medical Campus

St Louis, Missouri, 63110, United States

Location

Atlantic Health - Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

Carolinas Healthcare System

Charlotte, North Carolina, 28204, United States

Location

Hightower Clinical

Oklahoma City, Oklahoma, 73102, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Thompson Oncology Group - Knoxville - Downtown

Knoxville, Tennessee, 37916, United States

Location

SCRI - Tennessee Oncology - Nashville - Centennial

Nashville, Tennessee, 37203, United States

Location

University of Virginia Cancer Center

Nashville, Tennessee, 37232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Lumi Research

Houston, Texas, 77090, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Virginia Cancer Specialists - Fairfax Office

Fairfax, Virginia, 22031, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Peking University Cancer Hospital/Beijing Cancer Hospital

Beijing, Beijing Municipality, 100036, China

Location

Beijing Chest Hospital

Beijing, Beijing Municipality, 101149, China

Location

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

Location

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

The First Affiliated Hospital, Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

Thoraxklinik Heidelberg

Heidelberg, Baden-Wurttemberg, 69126, Germany

Location

HELIOS Klinikum Emil von Behring

Berlin, 14165, Germany

Location

Istituto Di Ricovero E Cura A Carattere Scientifico - Istituto Europeo Di Oncologia

Milan, 20141, Italy

Location

Azienda Ospedaliero Universitaria di Parma

Parma, 43126, Italy

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

Kurume University Hospital

Kurume-shi, Fukuoka, 830-0011, Japan

Location

Sendai Kousei Hospital

Sendai, Miyagi, 980-0873, Japan

Location

Kindai University Hospital

Ōsaka-sayama, Osaka, 589-8511, Japan

Location

In Situ Global Clinical Trials Network

Manatí, 00674, Puerto Rico

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Complejo Hospitalario Universitario A Coruna

A Coruña, LA Coruna, 15006, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

National Cheng Kung University Hospital

Tainan, Tainan CITY, 70403, Taiwan

Location

National Taiwan University Hospital - YunLin Branch

Douliu, Yunlin, 640, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 407, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

The Royal Marsden NHS Foundation Trust

London, England, SW3 6JJ, United Kingdom

Location

Related Publications (9)

• Zhou YF, Wang GX, Yang RN, Qi H, Fan YY, Li WY, Zhao GA, Hao GL, Lin F, Chen ZG. Electrophysiological consequences of acute mobocertinib exposure in isolated rat and guinea-pig hearts and transfected cell lines. Biochem Biophys Res Commun. 2025 Sep 16;780:152460. doi: 10.1016/j.bbrc.2025.152460. Epub 2025 Aug 7.

  PMID: 40818285 DERIVED

• Ou SI, Lin HM, Hong JL, Yin Y, Jin S, Lin J, Mehta M, Zhang P, Nguyen D, Neal JW. Comparative effectiveness of mobocertinib and standard of care in patients with NSCLC with EGFR exon 20 insertion mutations: An indirect comparison. Lung Cancer. 2023 May;179:107186. doi: 10.1016/j.lungcan.2023.107186. Epub 2023 Apr 1.

  PMID: 37075617 DERIVED

• Christopoulos P, Prawitz T, Hong JL, Lin HM, Hernandez L, Jin S, Tan M, Proskorovsky I, Lin J, Zhang P, Patel JD, Ou SI, Thomas M, Stenzinger A. Indirect comparison of mobocertinib and real-world therapies for pre-treated non-small cell lung cancer with EGFR exon 20 insertion mutations. Lung Cancer. 2023 May;179:107191. doi: 10.1016/j.lungcan.2023.107191. Epub 2023 Apr 8.

  PMID: 37058788 DERIVED

• Ou SI, Hong JL, Christopoulos P, Lin HM, Vincent S, Churchill EN, Soeda J, Kazdal D, Stenzinger A, Thomas M. Distribution and Detectability of EGFR Exon 20 Insertion Variants in NSCLC. J Thorac Oncol. 2023 Jun;18(6):744-754. doi: 10.1016/j.jtho.2023.01.086. Epub 2023 Feb 3.

  PMID: 36738930 DERIVED

• Yang JC, Zhou C, Janne PA, Ramalingam SS, Kim TM, Riely GJ, Spira AI, Piotrowska Z, Mekhail T, Garcia Campelo MR, Felip E, Bazhenova L, Jin S, Kaur M, Diderichsen PM, Gupta N, Bunn V, Lin J, N Churchill E, Mehta M, Nguyen D. Characterization and management of adverse events observed with mobocertinib (TAK-788) treatment for EGFR exon 20 insertion-positive non-small cell lung cancer. Expert Rev Anticancer Ther. 2023 Jan;23(1):95-106. doi: 10.1080/14737140.2023.2157815. Epub 2022 Dec 28.

  PMID: 36537204 DERIVED

• Duke ES, Stapleford L, Drezner N, Amatya AK, Mishra-Kalyani PS, Shen YL, Maxfield K, Zirkelbach JF, Bi Y, Liu J, Zhang X, Wang H, Yang Y, Zheng N, Reece K, Wearne E, Glen JJ, Ojofeitimi I, Scepura B, Nair A, Bikkavilli RK, Ghosh S, Philip R, Pazdur R, Beaver JA, Singh H, Donoghue M. FDA Approval Summary: Mobocertinib for Metastatic Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations. Clin Cancer Res. 2023 Feb 1;29(3):508-512. doi: 10.1158/1078-0432.CCR-22-2072.

  PMID: 36112541 DERIVED

• Zhou C, Ramalingam SS, Kim TM, Kim SW, Yang JC, Riely GJ, Mekhail T, Nguyen D, Garcia Campelo MR, Felip E, Vincent S, Jin S, Griffin C, Bunn V, Lin J, Lin HM, Mehta M, Janne PA. Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial. JAMA Oncol. 2021 Dec 1;7(12):e214761. doi: 10.1001/jamaoncol.2021.4761. Epub 2021 Dec 16.

  PMID: 34647988 DERIVED

• Han H, Li S, Chen T, Fitzgerald M, Liu S, Peng C, Tang KH, Cao S, Chouitar J, Wu J, Peng D, Deng J, Gao Z, Baker TE, Li F, Zhang H, Pan Y, Ding H, Hu H, Pyon V, Thakurdin C, Papadopoulos E, Tang S, Gonzalvez F, Chen H, Rivera VM, Brake R, Vincent S, Wong KK. Targeting HER2 Exon 20 Insertion-Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor Mobocertinib. Cancer Res. 2021 Oct 15;81(20):5311-5324. doi: 10.1158/0008-5472.CAN-21-1526. Epub 2021 Aug 11.

  PMID: 34380634 DERIVED

• Riely GJ, Neal JW, Camidge DR, Spira AI, Piotrowska Z, Costa DB, Tsao AS, Patel JD, Gadgeel SM, Bazhenova L, Zhu VW, West HL, Mekhail T, Gentzler RD, Nguyen D, Vincent S, Zhang S, Lin J, Bunn V, Jin S, Li S, Janne PA. Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations from a Phase I/II Trial. Cancer Discov. 2021 Jul;11(7):1688-1699. doi: 10.1158/2159-8290.CD-20-1598. Epub 2021 Feb 25.

  PMID: 33632775 DERIVED

Related Links

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MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

mobocertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 14, 2016
• First Posted: March 23, 2016
• Study Start: June 16, 2016
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: February 25, 2026

Record last verified: 2026-02

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

JP (4); DE (2); ES (3); IT (2); US (36); KR (4); PR (1); CN (5); GB (1); TW (4)