Clinical trial NCT02716116: A Study of TAK-788 in Adults With Non-Small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-03-23
Enrollment: 334
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part 1, Dose Escalation Component: Recommended Phase 2 Dose (RP2D) of Orally Administered TAK-788
timeFrame: Cycle 1 (Cycle length is equal to [=] 28 days)
measure: Part 2, Expansion Cohorts 1, 2, 4, 5 and 7: Confirmed Objective Response Rate (ORR) Assessed by the Investigator
timeFrame: Up to 36 months after first dose
measure: Part 2, Expansion Cohort 3: Intracranial ORR (iORR) Assessed by Independent Review Committee (IRC)
timeFrame: Up to 36 months after first dose
measure: Part 2, Expansion Cohort 6: Confirmed ORR Assessed by IRC
timeFrame: Up to 36 months after first dose
measure: Part 3, Extension Cohort: Confirmed ORR Assessed by IRC
timeFrame: Up to 36 months after first dose
Secondary outcomes:
measure: Part 1, Dose Escalation Component: Dose Limiting Toxicities (DLTs) of TAK-788
timeFrame: Cycle 1 (Cycle length=28 days)
measure: Part 1, Dose Escalation Component: Maximum Tolerated Dose (MTD) of TAK-788
timeFrame: Cycle 1 (Cycle length=28 days)
measure: Parts 1 and 2, Dose Escalation and Expansion Cohorts: Cmax; Maximum Observed Concentration of TAK-788 and its Metabolites
timeFrame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2)
measure: 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
timeFrame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2)
measure: 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
timeFrame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2)
measure: 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
timeFrame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2)
measure: Parts 1 and 2, Dose Escalation and Expansion Cohorts: RAC (Cmax): Accumulation Ratio Based on Cmax of TAK-788 and its Metabolites
timeFrame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2)
measure: Parts 1 and 2, Dose Escalation and Expansion Cohorts: RAC (AUC): Accumulation Ratio Based on AUC of TAK-788 and its Metabolites
timeFrame: Cycle 1 Day 1 and Cycle 2 Day 1 (cycle length=28 days for Parts 1 and 2)
measure: Part 2, Expansion Cohorts 1, 2, 3, 4, 5, and 7: Confirmed ORR as Assessed by IRC
timeFrame: Up to 36 months after first dose
measure: Part 2, Expansion Cohorts: Best Overall Response as Assessed by the Investigator and IRC
timeFrame: Up to 36 months after first dose
measure: Part 2, Expansion Cohorts: Best Target Lesion Response as Assessed by the Investigator and IRC
timeFrame: Up to 36 months after first dose
measure: Parts 2 and 3, Expansion and Extension Cohorts: Duration of Response as Assessed by the Investigator and IRC
timeFrame: Up to 36 months after first dose
measure: Parts 2 and 3, Expansion and Extension Cohorts: Disease Control Rate (DCR) as Assessed by the Investigator and IRC
timeFrame: Up to 36 months after first dose
measure: Part 2 and 3, Expansion and Extension Cohorts: Time to Response as Assessed by the Investigator and IRC
timeFrame: Up to 36 months after first dose
measure: Parts 2 and 3, Expansion and Extension Cohorts: Progression Free Survival (PFS) as Assessed by the Investigator and IRC
timeFrame: Up to 36 months after first dose
measure: Parts 2 and 3, Expansion and Extension Cohorts: Overall Survival (OS)
timeFrame: Up to 36 months after first dose
measure: Part 2, Expansion Cohort 3: Duration of Intracranial Response (iDOR)
timeFrame: up to 36 months after first dose
measure: Part 2, Expansion Cohort 3: Intracranial PFS (iPFS)
timeFrame: up to 36 months after first dose
measure: Part 2, Expansion Cohorts 6: Confirmed ORR as Assessed by the Investigator
timeFrame: Up to 36 months after first dose
measure: Part 3, Extension Cohort: Confirmed ORR as Assessed by the Investigator
timeFrame: Up to 36 months after first dose
measure: 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)
timeFrame: Up to 30 days after last dose of drug (approximately up to 37 months)
measure: 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)
timeFrame: Up to 30 days after last dose of drug (approximately up to 37 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Brookwood Medical Center
state: Alabama
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Tucson
country: United States
facility: The Oncology Institute of Hope and Innovation - West Tucson
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center - Duarte
state: California
city: Fountain Valley
country: United States
facility: Compassionate Cancer Care - Fountain Valley
state: California
city: La Jolla
country: United States
facility: University of California San Diego Moores Cancer Center
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group-Long Beach Elm
state: California
city: Los Alamitos
country: United States
facility: Cancer and Blood Specialty Clinic
state: California
city: Orange
country: United States
facility: University of California Irvine Health Chao Family Comprehensive Cancer Center
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center - Palo Alto
state: California
city: San Luis Obispo
country: United States
facility: SLO Oncology and Hematology Health Center
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Investigative Clinical Research - Indiana
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: Siteman Cancer Center - Washington University Medical Campus
state: Missouri
city: Morristown
country: United States
facility: Atlantic Health - Morristown Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Healthcare System
state: North Carolina
city: Oklahoma City
country: United States
facility: Hightower Clinical
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Knoxville
country: United States
facility: Thompson Oncology Group - Knoxville - Downtown
state: Tennessee
city: Nashville
country: United States
facility: SCRI - Tennessee Oncology - Nashville - Centennial
state: Tennessee
city: Nashville
country: United States
facility: University of Virginia Cancer Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Lumi Research
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists - Fairfax Office
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Beijing
country: China
facility: Peking University Cancer Hospital/Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Chest Hospital
state: Beijing
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University
state: Zhejiang
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg
state: Baden-wuerttemberg
city: Berlin
country: Germany
facility: HELIOS Klinikum Emil von Behring
city: Milano
country: Italy
facility: Istituto Di Ricovero E Cura A Carattere Scientifico - Istituto Europeo Di Oncologia
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Kurume-shi
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Sendai
country: Japan
facility: Sendai Kousei Hospital
state: Miyagi
city: Osaka-sayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Manati
country: Puerto Rico
facility: In Situ Global Clinical Trials Network
city: A Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruna
state: LA Coruna
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
state: Tainan CITY
city: Douliu
country: Taiwan
facility: National Taiwan University Hospital - YunLin Branch
state: Yunlin
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: England
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.