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

A Phase 1/2 Study of the Safety, Pharmacokinetics, and Anti-Tumor Activity of the Oral EGFR/HER2 Inhibitor TAK-788 (AP32788) in Non-Small Cell Lung Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: TAK-788

Detailed Description

This phase 1/2 study will evaluate the safety, pharmacokinetics, and anti-tumor activity of oral EGFR/HER2 Inhibitor TAK-788 in participants with NSCLC and anti-tumor activity of TAK-788 in participants with solid tumors other than NSCLC with EGFR or HER2 mutations. The trial will be conducted in three parts: a dose escalation (Part 1), expansion phase (Part 2), followed by an extension phase (Part 3).

The objectives of the dose escalation phase (Part 1), is to determine the safety profile of orally administered TAK-788, including the MTD, DLTs, RP2D, pharmacokinetic profile. The primary goal of the expansion component of the trial is to evaluate the anti-tumor activity of TAK-788 in seven histologically and molecularly defined cohorts at the RP2D (determined based on dose escalation phase of the trial).

The seven expansion cohorts will be:

1. NSCLC participants with EGFR exon 20 activating insertions, who have either not received or not shown an objective response to an EGFR TKI, and who have no active, measurable CNS metastases;
2. NSCLC participants with HER2 exon 20 activating insertions or point mutations and no active, measurable CNS metastases;
3. NSCLC participants with EGFR exon 20 activating insertions or HER2 exon 20 activating insertions or point mutations and active, measurable CNS metastases;
4. 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;
5. 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;
6. 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; and
7. Participants with solid tumors other than NSCLC with EGFR/HER2 mutations against which TAK-788 is active, without active CNS metastases.

The extension phase will evaluate efficacy of TAK-788 in participants with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations and who have been previously treated. The study enrolled 324 participants.

• Study Type: Interventional
• Enrollment (Estimated): 334
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100036
      • Peking University Cancer Hospital/Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China, 101149
      • Beijing Chest Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200433
      • Shanghai Pulmonary Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University
• Germany
  • Berlin, Germany, 14165
    • Helios Klinikum Emil Von Behring
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69126
      • Thoraxklinik Heidelberg
• Italy
  • Milan, Italy, 20141
    • Istituto Di Ricovero E Cura A Carattere Scientifico - Istituto Europeo Di Oncologia
  • Parma, Italy, 43126
    • Azienda Ospedaliero Universitaria di Parma
• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Fukuoka
    • Kurume-shi, Fukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 980-0873
      • Sendai Kousei Hospital
  • Osaka
    • Ōsaka-sayama, Osaka, Japan, 589-8511
      • Kindai University Hospital
• Puerto Rico
  • Manatí, Puerto Rico, 00674
    • In Situ Global Clinical Trials Network
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • LA Coruna
    • A Coruña, LA Coruna, Spain, 15006
      • Complejo Hospitalario Universitario A Coruña
• Taiwan
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Tainan CITY
    • Tainan, Tainan CITY, Taiwan, 70403
      • National Cheng Kung University Hospital
  • Yunlin
    • Douliu, Yunlin, Taiwan, 640
      • National Taiwan University Hospital - YunLin Branch
• United Kingdom
  • England
    • London, England, United Kingdom, SW3 6JJ
      • The Royal Marsden NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Brookwood Medical Center
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Tucson, Arizona, United States, 85745
      • The Oncology Institute of Hope and Innovation - West Tucson
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center - Duarte
    • Fountain Valley, California, United States, 92708
      • Compassionate Cancer Care - Fountain Valley
    • La Jolla, California, United States, 92093
      • University of California San Diego Moores Cancer Center
    • Long Beach, California, United States, 90813
      • Pacific Shores Medical Group-Long Beach Elm
    • Los Alamitos, California, United States, 90720
      • Cancer and Blood Specialty Clinic
    • Orange, California, United States, 92868
      • University of California Irvine Health Chao Family Comprehensive Cancer Center
    • Palo Alto, California, United States, 94305
      • Stanford Cancer Center - Palo Alto
    • San Luis Obispo, California, United States, 93405
      • SLO Oncology and Hematology Health Center
    • Whittier, California, United States, 90603
      • The Oncology Institute of Hope and Innovation
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Florida
    • Orlando, Florida, United States, 32804
      • AdventHealth Orlando
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Investigative Clinical Research - Indiana
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Siteman Cancer Center - Washington University Medical Campus
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health - Morristown Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Levine Cancer Institute
    • Charlotte, North Carolina, United States, 28204
      • Carolinas Healthcare System
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73102
      • Hightower Clinical
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • Thompson Oncology Group - Knoxville - Downtown
    • Nashville, Tennessee, United States, 37203
      • SCRI - Tennessee Oncology - Nashville - Centennial
    • Nashville, Tennessee, United States, 37232
      • University of Virginia Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • Houston, Texas, United States, 77090
      • Lumi Research
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists - Fairfax Office
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

General Inclusion Criteria all cohorts: dose escalation, antidiarrhea prophylaxis, dose escalation combination, expansion, and extension:

1. 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.
2. Must have sufficient tumor tissue available for analysis.
3. Must have measurable disease by response evaluation criteria in solid tumors (RECIST) v1.1.
4. Male or female adult participants (aged 18 years or older, or as defined per local regulations).
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
6. Minimum life expectancy of 3 months or more.
7. Adequate organ function at baseline.
8. 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.
9. Willingness and ability to comply with scheduled visits and study procedures.

Part 1: Dose Escalation Cohort Specific Inclusion Criteria:

1. Refractory to standard available therapies.

Part 2: Expansion Cohort 1 Specific Inclusion Criteria:

1. Have a documented EGFR in-frame exon 20 insertion by a local test.
2. Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
3. 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.

Expansion Cohort 2 Specific Inclusion Criteria:

1. Have one of the following documented by a local test:

   1. A HER2 exon 20 insertion;
   2. An activating point mutation in HER2.
2. Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
3. With an EGFR exon 20 insertion: Prior treatment with a pan-HER TKI (example, afatinib, neratinib, or dacomitinib) is allowed unless the participants had an objective response and subsequent progression as assessed by the investigator or treating physician.

Part 2: Expansion Cohort 3 Specific Inclusion Criteria:

1. Have one of the following documented by a local test:

   1. An EGFR exon 20 insertion;
   2. A HER2 exon 20 insertion;
   3. An activating point mutation in HER2.
2. Previously treated with one or more regimen of systemic therapy for locally advanced or metastatic disease.
3. For participants with an EGFR exon 20 insertion: 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.
4. For participants with a HER2 exon 20 insertion or HER2 activating point mutation: prior treatment with a pan-HER TKI (example, afatinib, neratinib, or dacomitinib) is allowed unless the participants had an objective response and subsequent progression as assessed by the investigator or treating physician during treatment with that prior TKI.
5. Have either previously untreated intracranial CNS metastases or previously treated intracranial CNS metastases with radiologically documented new or progressing CNS lesions.
6. Have at least one target (that is, measurable) intracranial CNS lesion (greater than or equal to [ ≥ ]10 millimeter [mm] in longest diameter by contrast enhanced magnetic resonance imaging [MRI]).

Part 2: Expansion Cohort 4 Specific Inclusion Criteria:

1. Have one of the following documented by a local test: an activating mutation in EGFR including exon 19 deletions or exon 21 L858R substitution (with or without T790M), or an uncommon activating mutation other than exon 20 insertion including, but not limited to, G719X (where X is any other amino acid), S768I, L861Q, or L861R.
2. Treatment naive for locally advanced or metastatic disease or previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.

Part 2: Expansion Cohort 5 Specific Inclusion Criteria:

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.

1. Have a documented EGFR in-frame exon 20 insertion by a local test.
2. Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease.
3. Previously showed an objective response to an EGFR TKI, and subsequently progressed as assessed by the investigator or treating physician.

Part 2: Expansion Cohort 6 Specific Inclusion Criteria:

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.

1. Have a documented EGFR in-frame exon 20 insertion by a local test.
2. No prior systemic treatment for locally advanced or metastatic disease.

Part 2: Expansion Cohort 7 Specific Inclusion Criteria:

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

1. Have a solid tumor that is not NSCLC, including, but not limited to, bladder/urinary tract cancer, breast cancer, gastric/esophageal cancer, biliary tract cancer, and head and neck cancer.
2. Is refractory to standard therapy.
3. Have EGFR or HER2 mutations, documented by a local test.

Part 3: Extension Cohort Specific Inclusion Criteria:

1. Have a documented EGFR in-frame exon 20 insertion by a local test and sufficient tumor tissue available for central analysis.

2. Must have received at least 1 prior line of therapy for locally advanced or metastatic disease and no more than 2 regimens of systemic anticancer chemotherapies for locally advanced or metastatic disease.

   • Prior treatment with an EGFR TKI is allowed unless the participant had an objective response and subsequent progression as assessed by the investigator or treating physician during treatment with that prior TKI.

Exclusion Criteria:

1. Previously received TAK-788.
2. 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).
3. Received antineoplastic monoclonal antibodies including immunotherapy within 28 days of the first dose of TAK-788.

4. 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.

   Note: This exclusion criteria does not apply to Expansion Cohort 7.

5. 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
6. Received a moderate or strong CYP4503A inhibitor or moderate or strong CYP3A inducer within 10 days prior to first dose of TAK-788.
7. 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.

8. 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.

9. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic).
10. Have significant, uncontrolled, or active cardiovascular disease.
11. Have a known history of uncontrolled hypertension. Participants with hypertension should be under treatment on study entry to control blood pressure.
12. Have prolonged QTcF interval, or being treated with medications known to be associated with the development of torsades de pointes.
13. Have an ongoing or active infection, including but not limited to, the requirement for intravenous (IV) antibiotics, or a known history of human immunodeficiency virus, hepatitis B virus (HBV), or hepatitis C virus (HCV). Testing is not required in the absence of history.
14. Currently have or have a history of interstitial lung disease, radiation pneumonitis that required steroid treatment, or drug-related pneumonitis.

15. Female participants who are lactating and breastfeeding or have a positive urine or serum pregnancy test during the screening period.

    Note: Female participants who are lactating will be eligible if they discontinue breastfeeding.

16. Have gastrointestinal illness or disorder that could affect oral absorption of TAK-788.
17. Have any condition or illness that, in the opinion of the investigator, might compromise participant safety or interfere with the evaluation of the safety of the drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation Component; TAK-788 treatment for participants with advanced NSCLC.	Drug: TAK-788; TAK-788 capsules.; Other Names: AP32788
Experimental: Part 2: Expansion Cohort 1; 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; TAK-788 capsules.; Other Names: AP32788
Experimental: Part 2: Expansion Cohort 2; TAK-788 treatment for NSCLC participants with HER2 exon 20 activating insertions or point mutations and no active, measurable CNS metastases.	Drug: TAK-788; TAK-788 capsules.; Other Names: AP32788
Experimental: Part 2: Expansion Cohort 3; 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; TAK-788 capsules.; Other Names: AP32788
Experimental: Part 2: Expansion Cohort 4; 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; TAK-788 capsules.; Other Names: AP32788
Experimental: Part 2: Expansion Cohort 5; 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; TAK-788 capsules.; Other Names: AP32788
Experimental: Part 2: Expansion Cohort 6; 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; TAK-788 capsules.; Other Names: AP32788
Experimental: Part 2: Expansion Cohort 7; 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; TAK-788 capsules.; Other Names: AP32788
Experimental: Part 3: Extension Cohort; TAK-788 treatment for participants with previously treated locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations.	Drug: TAK-788; TAK-788 capsules.; Other Names: AP32788

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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)
Parts 1 and 2, Dose Escalation and Expansion Cohorts: AUCt: Area Under the Concentration-time Curve from Time Zero to Time t for 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: RAC (Cmax): Accumulation Ratio Based on 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: RAC (AUC): Accumulation Ratio Based on AUC of TAK-788 and its Metabolites	Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2)
Part 2, Expansion Cohorts 1, 2, 3, 4, 5, and 7: Confirmed ORR as Assessed by IRC	Up to 36 months after first dose
Part 2, Expansion Cohorts: Best Overall Response as Assessed by the Investigator and IRC	Up to 36 months after first dose
Part 2, Expansion Cohorts: Best Target Lesion Response as Assessed by the Investigator and IRC	Up to 36 months after first dose
Parts 2 and 3, Expansion and Extension Cohorts: Duration of Response as Assessed by the Investigator and IRC	Up to 36 months after first dose
Parts 2 and 3, Expansion and Extension Cohorts: Disease Control Rate (DCR) as Assessed by the Investigator and IRC	Up to 36 months after first dose
Part 2 and 3, Expansion and Extension Cohorts: Time to Response as Assessed by the Investigator and IRC	Up to 36 months after first dose
Parts 2 and 3, Expansion and Extension Cohorts: Progression Free Survival (PFS) as Assessed by the Investigator and IRC	Up to 36 months after first dose
Parts 2 and 3, Expansion and Extension Cohorts: Overall Survival (OS)	Up to 36 months after first dose
Part 2, Expansion Cohort 3: Duration of Intracranial Response (iDOR)	up to 36 months after first dose
Part 2, Expansion Cohort 3: Intracranial PFS (iPFS)	up to 36 months after first dose
Part 2, Expansion Cohorts 6: Confirmed ORR as Assessed by the Investigator	Up to 36 months after first dose
Part 3, Extension Cohort: Confirmed ORR as Assessed by the Investigator	Up to 36 months after first dose
Part 3, Number of Participants With Patient-reported Symptoms (Lung Cancer), Functioning, and Health-related Quality of Life (HRQoL) Based on European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-core 30 (EORTC QLQ-C30)	Up to 30 days after last dose of drug (approximately up to 37 months)
Part 3, Extension Cohort: Number of Participants With Patient-reported Symptoms (Lung Cancer), Functioning, and health-related Global Quality of Life (HRQoL) Based on Quality of Life Questionnaire Lung Cancer Module-13 (QLQ-LC13)	Up to 30 days after last dose of drug (approximately up to 37 months)

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• Click here to ask Takeda's chatbot for comprehensive and easy-to-understand information about clinical trials - even across products and indications - in your local language.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2016
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: March 14, 2016
• First Submitted That Met QC Criteria: March 17, 2016
• First Posted (Estimated): March 23, 2016

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Tyrosine Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; mobocertinib
• Other Study ID Numbers: AP32788-15-101; U1111-1217-7205 (Registry Identifier: WHO); 2016-001271-68 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No