Clinical Trials List
Protocol NumberT1519
2019-04-01 - 2022-12-31
Phase II
Recruiting8
ICD-10 C34.9
Malignant neoplasm of unspecified part of bronchus or lung
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Phase 2 trial of durvalumab (MEDI4736) and tremelimumab with chemotherapy in metastatic EGFR mutant non-squamous non-small cell lung cancer (NSCLC) following progression on EGFR Tyrosine Kinase Inhibitors (TKIs)
-
Trial Applicant
National Health Research Institutes
-
Sponsor
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 林宗哲 Division of Hematology & Oncology
- Chong-Jen Yu Division of General Internal Medicine
- 許嘉林 Division of General Internal Medicine
- Jih-Hsiang Lee Division of Hematology & Oncology
- JIN-YUAN SHIH Division of General Internal Medicine
- 蔡子修 Division of General Internal Medicine
- 林育麟 Division of Hematology & Oncology
- 廖斌志 Division of Hematology & Oncology
- 廖唯昱 Division of General Internal Medicine
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- Chia-Chi Lin Division of Hematology & Oncology
- 徐偉勛 Division of Hematology & Oncology
- 陳冠宇 Division of General Internal Medicine
- 楊景堯 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chao-Hua Chiu Division of Hematology & Oncology
- Heng-Sheng Chao Division of Thoracic Medicine
- Chi-Lu Chiang Division of Thoracic Medicine
- 蕭慈慧 Division of Thoracic Medicine
- 楊朝能 Division of Thoracic Medicine
- 趙恒勝 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- TSUNG -YING YANG Division of Thoracic Medicine
- YEN-HSIANG HUANG Division of Thoracic Medicine
- 陳焜結 Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Shang-Yin Wu Division of General Internal Medicine
- Yu-Min Yeh Division of General Internal Medicine
- Wen-Pin Su Division of General Internal Medicine
- Chien-Chung Lin Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 陳宇欽 Division of Hematology & Oncology
- 陳佳宏 Division of Hematology & Oncology
- 張平穎 Division of Hematology & Oncology
- 葉人華 Division of Hematology & Oncology
- 戴明燊 Division of Hematology & Oncology
- 黃子權 Division of Hematology & Oncology
- 吳宜穎 Division of Hematology & Oncology
- 賴學緯 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
15 Recruiting
Condition/Disease
non-squamous non-small cell lung cancer
Objectives
To evaluate the efficacy and tolerability of dual blockade combination durvalumab and tremelimumab with platinum-pemetrexed in patients with metastatic NSCLC (T790+ve or T790M-ve) following progression on EGFR Tyrosine Kinase Inhibitors.
Test Drug
Durvalumab、Tremelimumab
Active Ingredient
Humanized anti-PD-1 mAb
Dosage Form
Injection
Dosage
50 mg/mL
20 mg/mL
20 mg/mL
Endpoints
1. Primary endpoint(s):
• Objective tumor response rate (OTRR) as defined by RECIST 1.1
2. Secondary endpoints:
• Disease control (DCR=CR + PR + SD) as defined by RECIST 1. 1
• OTRR as defined by iRECIST (OTR=confirmed CR or PR)
• Progression-free survival (PFS) as defined by RECIST 1.1 and iRECIST
• Progression-free survival at 12 months (PFS12) as defined by RECIST 1.1 and iRECIST
• Overall survival
• Treatment-related toxicity according to CTCAE, Version 5.0
• Objective tumor response rate (OTRR) as defined by RECIST 1.1
2. Secondary endpoints:
• Disease control (DCR=CR + PR + SD) as defined by RECIST 1. 1
• OTRR as defined by iRECIST (OTR=confirmed CR or PR)
• Progression-free survival (PFS) as defined by RECIST 1.1 and iRECIST
• Progression-free survival at 12 months (PFS12) as defined by RECIST 1.1 and iRECIST
• Overall survival
• Treatment-related toxicity according to CTCAE, Version 5.0
Inclution Criteria
1. Adults, aged 18 years and older (subjects from Taiwan must be 20 years or older) with histologically and/or cytologically confirmed non-squamous non-small cell lung cancer with
EGFR mutation of Exon 19 deletion or Exon 21 L858R point mutation.
• Patients with co-mutations are allowed as long as one of the mutation is either Exon19 deletion or Exon 21 L858R point mutation
2. Disease that has progressed and either:
(i) No evidence of EGFR T790M resistance mutation in both tissue re-biopsy and plasma after EGFR tyrosine kinase inhibitor therapy (TKI)*
OR
(ii) T790M mutation (detected in tissue re-biopsy, plasma or both) and progression on 3rd generation EGFR TKI; patients are allowed to have one prior line of TKI therapy before 3rd generation TKI
3. Measurable disease according to RECIST 1.1.
4. ECOG performance status of 0 or 1.
5. Adequate bone marrow function as defined below (within 14 days prior to registration and with values within the ranges specified below):
• Platelets ≥100 x 109/L
• Absolute neutrophil count (ANC) ≥ 1.0 x 109/L (≥ 1000 per mm3)
• Haemoglobin ≥ 90 x g/L
6. Adequate liver function (within 14 days prior to registration and with values within the ranges specified below):
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x institutional upper limit of normal (ULN). (or ≤ 5 x ULN if liver metastases are present)
• Bilirubin ≤1.5 x ULN
7. Adequate renal function (within 14 days prior to registration):
• Measured creatinine clearance >40 mL/min or Calculated creatinine clearance >40 mL/min by the Cockcroft-Gault formula92 (Appendix 4) or by 24-hour urine collection for determination of creatinine clearance
8. Provision of a pre-treatment tumour tissue sample from a biopsy taken within 42 days prior to enrolment (core biopsy preferred) to determine NSCLC histology and for translational
research
9. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Age-specific definitions of post-menopausal status are presented
in Appendix 5.
10. Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
11. Signed written informed consent (main study and optional biobanking).
EGFR mutation of Exon 19 deletion or Exon 21 L858R point mutation.
• Patients with co-mutations are allowed as long as one of the mutation is either Exon19 deletion or Exon 21 L858R point mutation
2. Disease that has progressed and either:
(i) No evidence of EGFR T790M resistance mutation in both tissue re-biopsy and plasma after EGFR tyrosine kinase inhibitor therapy (TKI)*
OR
(ii) T790M mutation (detected in tissue re-biopsy, plasma or both) and progression on 3rd generation EGFR TKI; patients are allowed to have one prior line of TKI therapy before 3rd generation TKI
3. Measurable disease according to RECIST 1.1.
4. ECOG performance status of 0 or 1.
5. Adequate bone marrow function as defined below (within 14 days prior to registration and with values within the ranges specified below):
• Platelets ≥100 x 109/L
• Absolute neutrophil count (ANC) ≥ 1.0 x 109/L (≥ 1000 per mm3)
• Haemoglobin ≥ 90 x g/L
6. Adequate liver function (within 14 days prior to registration and with values within the ranges specified below):
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x institutional upper limit of normal (ULN). (or ≤ 5 x ULN if liver metastases are present)
• Bilirubin ≤1.5 x ULN
7. Adequate renal function (within 14 days prior to registration):
• Measured creatinine clearance >40 mL/min or Calculated creatinine clearance >40 mL/min by the Cockcroft-Gault formula92 (Appendix 4) or by 24-hour urine collection for determination of creatinine clearance
8. Provision of a pre-treatment tumour tissue sample from a biopsy taken within 42 days prior to enrolment (core biopsy preferred) to determine NSCLC histology and for translational
research
9. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Age-specific definitions of post-menopausal status are presented
in Appendix 5.
10. Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
11. Signed written informed consent (main study and optional biobanking).
Exclusion Criteria
Exclusion criteria
1. Prior immunotherapy with checkpoint inhibitors, including prior anti-PD-1/anti-PD-L1 or antiCTLA-4 antibodies.
2. Prior chemotherapy for advanced NSCLC.
• For recurrent, incurable disease, prior adjuvant chemotherapy or concurrent chemotherapy and radiotherapy with curative intent is allowed, but must have been completed more than 6 months ago.
3.Life expectancy of less than 3 months.
4.Current enrolment or participation in another clinical study with an unregistered investigational product during the last 12 months, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study must first
be discussed with ILLUMINATE Study Team (illuminate@ctc.usyd.edu.au)) before study enrolment.
5.Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
6.Radiotherapy or major surgery (as defined by the local investigator) within 4 weeks of the first dose of study drug. Note the following exceptions, which have a 2-week washout:
• Local surgery on isolated lesions for palliative intent
• Radiotherapy to control CNS disease identified during screening
7.History of pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary function
8.History of active primary immunodeficiency or allogeneic transplant.
9.Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis (with the exception ofdiverticulosis), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone
replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone
10.Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
11.History of another primary malignancy except for
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease.
12.Spinal cord compression, symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids equivalent to oral
prednisone of 10mg/day or greater, and have a stable neurological status for at least 2 weeks after commencement of the definitive therapy. Patients with asymptomatic brain metastases can be eligible for inclusion if in the opinion of the Investigator immediate definitive treatment is not indicated.
13.Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of
HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
14.Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
15.Live attenuated vaccine within 30 days prior to the first dose of study drug, whilst receiving study drug and up to 30 days after the last dose of study drug.
16.Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
17.Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after
the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab plus tremelimumab combination therapy.
18.Known allergy or hypersensitivity to any of the study drugs or excipients
1. Prior immunotherapy with checkpoint inhibitors, including prior anti-PD-1/anti-PD-L1 or antiCTLA-4 antibodies.
2. Prior chemotherapy for advanced NSCLC.
• For recurrent, incurable disease, prior adjuvant chemotherapy or concurrent chemotherapy and radiotherapy with curative intent is allowed, but must have been completed more than 6 months ago.
3.Life expectancy of less than 3 months.
4.Current enrolment or participation in another clinical study with an unregistered investigational product during the last 12 months, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study must first
be discussed with ILLUMINATE Study Team (illuminate@ctc.usyd.edu.au)) before study enrolment.
5.Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
6.Radiotherapy or major surgery (as defined by the local investigator) within 4 weeks of the first dose of study drug. Note the following exceptions, which have a 2-week washout:
• Local surgery on isolated lesions for palliative intent
• Radiotherapy to control CNS disease identified during screening
7.History of pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary function
8.History of active primary immunodeficiency or allogeneic transplant.
9.Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis (with the exception ofdiverticulosis), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone
replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone
10.Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
11.History of another primary malignancy except for
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease.
12.Spinal cord compression, symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids equivalent to oral
prednisone of 10mg/day or greater, and have a stable neurological status for at least 2 weeks after commencement of the definitive therapy. Patients with asymptomatic brain metastases can be eligible for inclusion if in the opinion of the Investigator immediate definitive treatment is not indicated.
13.Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of
HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
14.Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
15.Live attenuated vaccine within 30 days prior to the first dose of study drug, whilst receiving study drug and up to 30 days after the last dose of study drug.
16.Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
17.Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after
the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab plus tremelimumab combination therapy.
18.Known allergy or hypersensitivity to any of the study drugs or excipients
The Estimated Number of Participants
-
Taiwan
50 participants
-
Global
100 participants
