Clinical Trials List
Protocol NumberHR-BLTN-Ⅲ-NSCLC
Active
2020-10-15 - 2026-03-31
Phase III
Recruiting3
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
ICD-10C34.91
Malignant neoplasm of unspecified part of right bronchus or lung
ICD-10C34.92
Malignant neoplasm of unspecified part of left bronchus or lung
ICD-10C7A.090
Malignant carcinoid tumor of the bronchus and lung
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Phase 3, Randomized, Open-label, Multicenter Study of the Efficacy and Safety of Pyrotinib versus Docetaxel in Patients with Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Harboring a HER2 Exon 20 Mutation who Progressed on or after Treatment with Platinum Based Chemotherapy
-
Trial Applicant
MEDPACE TAIWAN LIMITED
-
Sponsor
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Yung-Hung Luo Division of Thoracic Medicine
- Chia-I Shen Division of Thoracic Medicine
- Chi-Lu Chiang Division of Thoracic Medicine
- 趙恒勝 Division of Thoracic Medicine
- Heng-Sheng Chao Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Wen-Cheng Chang Division of Hematology & Oncology
- Ping-Chih Hsu Division of Hematology & Oncology
- 邱立忠 Division of Hematology & Oncology
- Chih-Hung Chen Division of Hematology & Oncology
- 枋岳甫 Division of Hematology & Oncology
- 林定佑 Division of Hematology & Oncology
- Chien-Ying Liu Division of Hematology & Oncology
- 柯皓文 無
- 吳教恩 Division of Hematology & Oncology
- Chih-Hsi Kuo Division of Hematology & Oncology
- Chih-Liang Wang Division of Hematology & Oncology
- Shih-Hong Li Division of Hematology & Oncology
- Chih-Hung Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chih-Yen Tu Division of Thoracic Medicine
- 陳鴻仁 Division of Thoracic Medicine
- Chia-Hsiang Li Division of Thoracic Medicine
- Yu-Chao Lin Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
non-small cell lung cancer (NSCLC) harboring a HER2 exon 20 mutation
Objectives
Primary Objective:
To compare the progression-free survival (PFS) of pyrotinib versus
docetaxel in patients with advanced non-squamous non-small cell
lung cancer (NSCLC) harboring a HER2 exon 20 mutation who progressed after treatment with platinum based chemotherapy). The
PFS endpoint will be determined by blinded independent radiology
review committee (BIRC).
Secondary Objectives:
To compare the efficacy of pyrotinib versus docetaxel in patients
with advanced HER2 exon20-mutated non-squamous NSCLC who
have progressed after treatment with platinum based chemotherapy,
through evaluations of overall survival (OS), and objective response
rate (ORR), disease control rate (DCR), duration of response (DoR),
and time to tumor progression (TTP) assessed by BIRC, and ORR,
DCR, DoR, TTP, PFS and PFS2 assessed by investigator;
To evaluate the safety of pyrotinib versus docetaxel in patients with
advanced HER2 exon20-mutated non-squamous NSCLC who have
progressed after treated with platinum based chemotherapy;
To evaluate patient reported outcomes (PRO) in pyrotinib versus
docetaxel treatment arms;
To evaluate pharmacokinetics (PK) of pyrotinib in patients with
advanced HER2 exon20-mutated non-squamous NSCLC who have
progressed after treatment with platinum based chemotherapy.
Test Drug
Pyrotinib Maleate Tablet
Active Ingredient
Pyrotinib Maleate
Dosage Form
film-coated tablet
Dosage
80 mg/tablet、160 mg/tablet
Endpoints
PFS evaluated by the blinded independent review committee (BIRC)
based on Response Evaluation Criteria in Solid Tumors Version 1.1
(RECIST v1.1).
based on Response Evaluation Criteria in Solid Tumors Version 1.1
(RECIST v1.1).
Inclution Criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Signed and dated written informed consent which is approved by
IRB/EC, willing and able to comply with scheduled treatment, all
examinations at study visits, and other study procedures.
2. Male or female, ≥18 years old.
3. ECOG PS 0-1 (see Error! Reference source not found. for ECOG
PS criteria).
4. Have histologically or cytologically confirmed locally advanced
(must have been evaluated by the investigator that are not amenable
to curable surgery or radiotherapy) or metastatic non-squamous
NSCLC disease (Stage IIIB – IV, according to the International
Association for the Study of Lung Cancer (IASLC) cancer staging
system, 8th edition [Error! Reference source not found.]).
5. Before enrollment, a documented confirmed presence of activating
mutations in exon 20 of the HER2 gene must be provided. Sufficient
tumor tissue samples should be provided to retrospectively confirm
the mutation status of the HER2 gene. For examples of HER2
(ERBB2) exon 20 mutations see Error! Reference source not
found..
The tumor tissue samples should be: neutral buffered formalin fixed,
paraffin-embedded [FFPE] blocks or at least 6-12 unstained (6-10
surgical biopsies, or at least 12 core needle biopsies) tumor tissue
slices, fresh or archived (fresh samples are preferred). For patients
who cannot provide the required biopsies, their enrollment can be
discussed with the sponsor.
6. Must have measureable disease per RECIST v1.1. The definition of
CT or MRI measurable lesion as the target lesion: according to
RECIST v1.1, the long diameter of such lesion should be ≥10 mm by
the spiral CT scan or the short diameter of enlarged lymph nodes ≥15mm; lesions that have previously received local treatment can be used as target lesions after the confirmation of progress according to the RECIST v1.1 standard.
7. For advanced NSCLC, patients must have had progressive disease on or after a platinum based chemotherapy, with or without immune
checkpoint inhibitors (PD-1/PD-L1 inhibitors) and/or anti-angiogenic
drugs. No more than 2 prior lines of systemic therapy are allowed.
Two scenarios of neoadjuvant/adjuvant therapy are allowed: a)
subjects who received adjuvant or neoadjuvant platinum based
chemotherapy and developed recurrent or metastatic disease within 6 months of completing therapy are eligible; b) subjects with recurrent disease > 6 months after adjuvant or neoadjuvant platinum-based chemotherapy, who also subsequently progressed during or after a platinum based regimen given to treat the recurrence, are eligible.
8. The laboratory test values must meet the following standards to
manifest that the functional level of important organs/systems meets
the requirements:
Hematology (not corrected by blood/blood products transfusion,
or transfusion of hematopoietic stimulating factors such as GCSF/TPO, etc. within 14 days before the test): ANC≥1.5 × 109/L；PLT≥100 × 109/L; Hb≥80 g/L;
Blood biochemistry (liver function): TBIL ≤ 1.0 × ULN; ALT
and/or AST ≤ 1.5 × ULN AND ALP≤2.5×ULN;
Blood biochemistry (renal function): Cr≤1.5 × ULN and
CrCL≥50 mL/min (Cockcroft-Gault formula);
9. Female of childbearing potential must have a serum pregnancy test
within 7 days before the first dose and the result is negative. Female
patient of childbearing potential (WOCBP) and male patient whose
partner is WOCBP must agree to use effective contraception method
during the study period and within 8 weeks after the last dose (if
receiving docetaxel treatment only, after the last dose, 3 months for
male patient whose partner is WOCBP, and 6 months for female
patient of childbearing potential).
1. Signed and dated written informed consent which is approved by
IRB/EC, willing and able to comply with scheduled treatment, all
examinations at study visits, and other study procedures.
2. Male or female, ≥18 years old.
3. ECOG PS 0-1 (see Error! Reference source not found. for ECOG
PS criteria).
4. Have histologically or cytologically confirmed locally advanced
(must have been evaluated by the investigator that are not amenable
to curable surgery or radiotherapy) or metastatic non-squamous
NSCLC disease (Stage IIIB – IV, according to the International
Association for the Study of Lung Cancer (IASLC) cancer staging
system, 8th edition [Error! Reference source not found.]).
5. Before enrollment, a documented confirmed presence of activating
mutations in exon 20 of the HER2 gene must be provided. Sufficient
tumor tissue samples should be provided to retrospectively confirm
the mutation status of the HER2 gene. For examples of HER2
(ERBB2) exon 20 mutations see Error! Reference source not
found..
The tumor tissue samples should be: neutral buffered formalin fixed,
paraffin-embedded [FFPE] blocks or at least 6-12 unstained (6-10
surgical biopsies, or at least 12 core needle biopsies) tumor tissue
slices, fresh or archived (fresh samples are preferred). For patients
who cannot provide the required biopsies, their enrollment can be
discussed with the sponsor.
6. Must have measureable disease per RECIST v1.1. The definition of
CT or MRI measurable lesion as the target lesion: according to
RECIST v1.1, the long diameter of such lesion should be ≥10 mm by
the spiral CT scan or the short diameter of enlarged lymph nodes ≥15mm; lesions that have previously received local treatment can be used as target lesions after the confirmation of progress according to the RECIST v1.1 standard.
7. For advanced NSCLC, patients must have had progressive disease on or after a platinum based chemotherapy, with or without immune
checkpoint inhibitors (PD-1/PD-L1 inhibitors) and/or anti-angiogenic
drugs. No more than 2 prior lines of systemic therapy are allowed.
Two scenarios of neoadjuvant/adjuvant therapy are allowed: a)
subjects who received adjuvant or neoadjuvant platinum based
chemotherapy and developed recurrent or metastatic disease within 6 months of completing therapy are eligible; b) subjects with recurrent disease > 6 months after adjuvant or neoadjuvant platinum-based chemotherapy, who also subsequently progressed during or after a platinum based regimen given to treat the recurrence, are eligible.
8. The laboratory test values must meet the following standards to
manifest that the functional level of important organs/systems meets
the requirements:
Hematology (not corrected by blood/blood products transfusion,
or transfusion of hematopoietic stimulating factors such as GCSF/TPO, etc. within 14 days before the test): ANC≥1.5 × 109/L；PLT≥100 × 109/L; Hb≥80 g/L;
Blood biochemistry (liver function): TBIL ≤ 1.0 × ULN; ALT
and/or AST ≤ 1.5 × ULN AND ALP≤2.5×ULN;
Blood biochemistry (renal function): Cr≤1.5 × ULN and
CrCL≥50 mL/min (Cockcroft-Gault formula);
9. Female of childbearing potential must have a serum pregnancy test
within 7 days before the first dose and the result is negative. Female
patient of childbearing potential (WOCBP) and male patient whose
partner is WOCBP must agree to use effective contraception method
during the study period and within 8 weeks after the last dose (if
receiving docetaxel treatment only, after the last dose, 3 months for
male patient whose partner is WOCBP, and 6 months for female
patient of childbearing potential).
Exclusion Criteria
Subjects presenting with any of the following will not be randomized into the trial:
1. Target disease exclusion criteria
1) Malignant tumors with other pathological types, such as mixed
cancer, double primary cancers;
2) Medical history of other active malignancies within last 5 years;
Exceptions: skin basal cell carcinoma, superficial bladder cancer, skin squamous cell carcinoma, prostate cancer in situ, or cervical
carcinoma in situ, for which by the date of the first dose of study
drug, at least 2 years of complete remission and no other
treatment is needed or expected during the study period.
3) Subjects with active CNS metastases are excluded. Subjects with
history or evidence of current leptomeningeal metastases are
excluded.
Subjects are eligible if CNS metastases are adequately treated
(surgery or radiotherapy) and subjects are neurologically returned
to baseline (except for residual signs or symptoms related to the
CNS treatment) for at least 2 weeks prior to enrollment. In
addition, subjects must be either off corticosteroids, or on a stable
or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
4) Previously treated with targeted drugs for HER2 gene mutations
(including but not limited to trastuzumab and its conjugated
drugs, pertuzumab, lapatinib, pyrotinib, neratinib, afatinib,
dacomitinib, poziotinib);
5) Previously treated with docetaxel;
6) By the date of first dose of study treatment, the washout period of
previous drug treatment / medical intervention does not meet the
following requirements:
• anti-tumor drugs such as platinum drugs, other chemotherapy
drugs, immune checkpoint inhibitors, etc. (including the study
drugs of the same classes in clinical study) ≥ 3 weeks (or 5
half-lives of the drug, to whichever is shorter);
• anti-tumor traditional Chinese medicine treatment ≥ 2 weeks;
• major surgery (requires hospitalization) ≥ 2 weeks;
• minimally invasive surgery (puncture, biopsy, endoscope, etc.)
≥ 1 week;
• with > 30 Gy non-thoracic radiotherapy ≥4 weeks;
• with > 30 Gy thoracic radiotherapy ≥24 weeks;
• with ≤30 Gy palliative radiotherapy ≥2 weeks.
Furthermore, it is required that the adverse event has resolved
from the previous drug treatment/medical interventions (except
for alopecia or fatigue within NCI-CTCAE v5.0 Grade 1).
2. Medical history exclusion criteria
1) Patients with active (not medically treated) CNS diseases, such as
benign brain tumors, benign meningiomas, other leptomeningeal
diseases, and poorly controlled (occurs within 6 months prior to
the first dose of study treatment) cerebrovascular accidents
(including transient ischemic attack, cerebral hemorrhage,
cerebral infarction, etc). Patients are eligible if the above-mentioned disease has been adequately treated and clinically stable prior to the first dose of study treatment (by radiological assessments [preferred enhanced MRI or CT] and maintained for at least 2 weeks, and the relevant symptoms have been resolved to NCI-CTCAE v5.0 Grade ≤1 for at least 2 weeks);
2) Severe cardiac disease, including the following diseases that
occur within 12 months prior to the first dose of study treatment:
(1) myocardial infarction; (2) heart failure; and disease that
occurs within 3 months prior to the first dose of study treatment:
(1) severe/unstable angina pectoris; (2) ventricular arrhythmias
requiring continuous medication; but controlled atrial arrhythmias
after continuous medication is eligible; (3) Grade ≥2 myocardial
ischemia; (4) Grade ≥2 cardiac insufficiency according to New
York Heart Association (NYHA) Functional Classification
(Error! Reference source not found.); (5) LVEF (left
ventricular ejection fraction) <50%; (6) coronary / peripheral
artery bypass grafting is experienced or expected; (7) QTcF> 450
ms (male)，QTcF > 470 ms (female) (QTc interval is calculated
by Fridericia formula; in case QTc is abnormal, it can be tested
for three times at an interval of 2 minutes and the average value
will be used); any other heart disease judged by the investigator to
be unsuitable for clinical study;
3) Prior to the first dose of study treatment, patients with the
following conditions: inability to swallow, chronic diarrhea,
intestinal obstruction, gastrointestinal perforation or gastrectomy,
colitis or other diseases or special conditions that affect drug
administration and absorption;
4) Prior to the first dose of study treatment, patients with severe
effusions with clinical symptoms (such as a large amount of
pleural effusion, ascites or pericardial effusion) require repeated
therapeutic puncture drainers (tube is allowed);
5) Within 2 weeks prior to the first dose of study treatment,
symptoms of severe infection or evidence for
microbiological/viral diagnosis, including but not limited to
hospitalization due to infection, bacteremia or severe pneumonia;
oral or intravenous administration of therapeutic antibiotics;
6) Congenital or acquired immunodeficiency (e.g., HIV infection);
7) Patients with active hepatitis infection. Patients are eligible if
HBV- deoxyribonucleic acid (DNA) < 500 IU/mL (or must be <
2500 copy/mL if copy/mL is the only unit available in the study
site; if the normal ranges of the study sites are different, the
positive standard must not be met), and have received anti-HBV
therapy for at least 14 days prior to the first dose of study
treatment (treatment in accordance with local standard of care,
e.g., entecavir) and are willing to receive antiviral therapy
throughout the study; patients with positive hepatitis C (HCV)
ribonucleic acid (RNA) must receive anti-viral therapy in accordance with the local standard treatment guideline and hepatic function resolve to CTCAE Grade ≤1;
3. Allergies and adverse drug reaction
1) History of allergy to the study drugs or components, such as
Tween-80-containing infusions.
4. Pregnancy or breastfeeding.
5. Concomitant treatments exclusion criteria
1) Within 2 weeks prior to the first dose of study treatment, or
during the study period, patients receive or are anticipated to
receive continuous strong CYP3A4 inducers or inhibitors, P-gp
inhibitors (see Error! Reference source not found., list of
common strong CYP3A4 inducers or inhibitors and P-gp
inhibitors), or medications that are known to cause QT/QTc
prolongation;
6. Others
1) Per investigator’s judgment, other diseases or laboratory evidence
that would cause serious threats to the safety of the patients, or
which are not in the best interest of the patient to participate in the
study are excluded(include but not limited: superior vena cava
syndrome, severe pulmonary disease [untreated tuberculosis,
pulmonary embolism that is untreated or occurred within 3
months prior to the first dose of study treatment, active
pneumonia other than obstructive pneumonia], uncontrolled
epilepsy or mental illness, planned organ transplantation in the
near future, a genetic or acquired bleeding tendency).
2) Per investigator’s judgment, other situations that may confuse the
study results or would affect the subjects’ ability to comply with
study procedures are excluded, such as alcoholism, drug abuse,
criminal detention, etc.
1. Target disease exclusion criteria
1) Malignant tumors with other pathological types, such as mixed
cancer, double primary cancers;
2) Medical history of other active malignancies within last 5 years;
Exceptions: skin basal cell carcinoma, superficial bladder cancer, skin squamous cell carcinoma, prostate cancer in situ, or cervical
carcinoma in situ, for which by the date of the first dose of study
drug, at least 2 years of complete remission and no other
treatment is needed or expected during the study period.
3) Subjects with active CNS metastases are excluded. Subjects with
history or evidence of current leptomeningeal metastases are
excluded.
Subjects are eligible if CNS metastases are adequately treated
(surgery or radiotherapy) and subjects are neurologically returned
to baseline (except for residual signs or symptoms related to the
CNS treatment) for at least 2 weeks prior to enrollment. In
addition, subjects must be either off corticosteroids, or on a stable
or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
4) Previously treated with targeted drugs for HER2 gene mutations
(including but not limited to trastuzumab and its conjugated
drugs, pertuzumab, lapatinib, pyrotinib, neratinib, afatinib,
dacomitinib, poziotinib);
5) Previously treated with docetaxel;
6) By the date of first dose of study treatment, the washout period of
previous drug treatment / medical intervention does not meet the
following requirements:
• anti-tumor drugs such as platinum drugs, other chemotherapy
drugs, immune checkpoint inhibitors, etc. (including the study
drugs of the same classes in clinical study) ≥ 3 weeks (or 5
half-lives of the drug, to whichever is shorter);
• anti-tumor traditional Chinese medicine treatment ≥ 2 weeks;
• major surgery (requires hospitalization) ≥ 2 weeks;
• minimally invasive surgery (puncture, biopsy, endoscope, etc.)
≥ 1 week;
• with > 30 Gy non-thoracic radiotherapy ≥4 weeks;
• with > 30 Gy thoracic radiotherapy ≥24 weeks;
• with ≤30 Gy palliative radiotherapy ≥2 weeks.
Furthermore, it is required that the adverse event has resolved
from the previous drug treatment/medical interventions (except
for alopecia or fatigue within NCI-CTCAE v5.0 Grade 1).
2. Medical history exclusion criteria
1) Patients with active (not medically treated) CNS diseases, such as
benign brain tumors, benign meningiomas, other leptomeningeal
diseases, and poorly controlled (occurs within 6 months prior to
the first dose of study treatment) cerebrovascular accidents
(including transient ischemic attack, cerebral hemorrhage,
cerebral infarction, etc). Patients are eligible if the above-mentioned disease has been adequately treated and clinically stable prior to the first dose of study treatment (by radiological assessments [preferred enhanced MRI or CT] and maintained for at least 2 weeks, and the relevant symptoms have been resolved to NCI-CTCAE v5.0 Grade ≤1 for at least 2 weeks);
2) Severe cardiac disease, including the following diseases that
occur within 12 months prior to the first dose of study treatment:
(1) myocardial infarction; (2) heart failure; and disease that
occurs within 3 months prior to the first dose of study treatment:
(1) severe/unstable angina pectoris; (2) ventricular arrhythmias
requiring continuous medication; but controlled atrial arrhythmias
after continuous medication is eligible; (3) Grade ≥2 myocardial
ischemia; (4) Grade ≥2 cardiac insufficiency according to New
York Heart Association (NYHA) Functional Classification
(Error! Reference source not found.); (5) LVEF (left
ventricular ejection fraction) <50%; (6) coronary / peripheral
artery bypass grafting is experienced or expected; (7) QTcF> 450
ms (male)，QTcF > 470 ms (female) (QTc interval is calculated
by Fridericia formula; in case QTc is abnormal, it can be tested
for three times at an interval of 2 minutes and the average value
will be used); any other heart disease judged by the investigator to
be unsuitable for clinical study;
3) Prior to the first dose of study treatment, patients with the
following conditions: inability to swallow, chronic diarrhea,
intestinal obstruction, gastrointestinal perforation or gastrectomy,
colitis or other diseases or special conditions that affect drug
administration and absorption;
4) Prior to the first dose of study treatment, patients with severe
effusions with clinical symptoms (such as a large amount of
pleural effusion, ascites or pericardial effusion) require repeated
therapeutic puncture drainers (tube is allowed);
5) Within 2 weeks prior to the first dose of study treatment,
symptoms of severe infection or evidence for
microbiological/viral diagnosis, including but not limited to
hospitalization due to infection, bacteremia or severe pneumonia;
oral or intravenous administration of therapeutic antibiotics;
6) Congenital or acquired immunodeficiency (e.g., HIV infection);
7) Patients with active hepatitis infection. Patients are eligible if
HBV- deoxyribonucleic acid (DNA) < 500 IU/mL (or must be <
2500 copy/mL if copy/mL is the only unit available in the study
site; if the normal ranges of the study sites are different, the
positive standard must not be met), and have received anti-HBV
therapy for at least 14 days prior to the first dose of study
treatment (treatment in accordance with local standard of care,
e.g., entecavir) and are willing to receive antiviral therapy
throughout the study; patients with positive hepatitis C (HCV)
ribonucleic acid (RNA) must receive anti-viral therapy in accordance with the local standard treatment guideline and hepatic function resolve to CTCAE Grade ≤1;
3. Allergies and adverse drug reaction
1) History of allergy to the study drugs or components, such as
Tween-80-containing infusions.
4. Pregnancy or breastfeeding.
5. Concomitant treatments exclusion criteria
1) Within 2 weeks prior to the first dose of study treatment, or
during the study period, patients receive or are anticipated to
receive continuous strong CYP3A4 inducers or inhibitors, P-gp
inhibitors (see Error! Reference source not found., list of
common strong CYP3A4 inducers or inhibitors and P-gp
inhibitors), or medications that are known to cause QT/QTc
prolongation;
6. Others
1) Per investigator’s judgment, other diseases or laboratory evidence
that would cause serious threats to the safety of the patients, or
which are not in the best interest of the patient to participate in the
study are excluded(include but not limited: superior vena cava
syndrome, severe pulmonary disease [untreated tuberculosis,
pulmonary embolism that is untreated or occurred within 3
months prior to the first dose of study treatment, active
pneumonia other than obstructive pneumonia], uncontrolled
epilepsy or mental illness, planned organ transplantation in the
near future, a genetic or acquired bleeding tendency).
2) Per investigator’s judgment, other situations that may confuse the
study results or would affect the subjects’ ability to comply with
study procedures are excluded, such as alcoholism, drug abuse,
criminal detention, etc.
The Estimated Number of Participants
-
Taiwan
12 participants
-
Global
150 participants
