Clinical Trials List
Protocol NumberD7815C00001
Not yet recruiting
2025-11-01 - 2033-12-31
Phase III
Recruiting9
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 III, open-label, randomized, multicenter, parallel-group trial evaluating the efficacy and safety of first-line trastuzumab deruxtecan combined with rilvegostomig or volrustomig versus pembrolizumab plus chemotherapy in locally advanced, unresectable, or metastatic HER2-overexpressing non-squamous NSCLC (DESTINY-Lung07).
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Trial Applicant
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Sponsor
AstraZeneca Taiwan Co., Ltd.
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Trial scale
Multi-Regional Multi-Center
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Update
2026/07/03
Investigators and Locations
Co-Principal Investigator
- Yuh-Min Chen 無
- Chi-Lu Chiang 無
- Hsu-ching Huang 無
- Chia-I Shen 無
- 趙恒勝 無
- 許志堅 無
- 廖映庭 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Tzeon-jye Chiou 無
- HsingJin Eugene Liu 無
- Ming-Chih Yu 無
- Chia-Lun Chang 無
- Shian-Jiun Lin 無
- Chih-Hsin Lee 無
- Yu-Tien Tzeng 無
- Hsin-Wei Huang 無
- Tzu-Yao Liao 無
- Kuan-Jen Bai 無
- Jer-Hwa Chang 無
- 江振源 無
- 石智元 無
- 楊善堯 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chia-Chi Lin 無
- Chong-Jen Yu 無
- James Chih-Hsin Yang 無
- 陳冠宇 無
- 廖唯昱 無
- CHAO-CHI HO CHAO-CHI HO 無
- 黃俊凱 無
- 吳尚俊 無
- 許嘉林 無
- Jih-Hsiang Lee 無
- 蔡子修 無
- 楊景堯 無
- 錢穎群 無
- 徐偉勛 無
- 廖斌志 無
- 林昭文 無
- YEN-TING LIN 無
- 于鎧綸 無
- 黃得瑞 無
- 張立群 無
- 黃信端 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 林宗哲 無
- Chia-Chi Lin 無
- JIN-YUAN SHIH 無
- 吳尚俊 無
- 廖斌志 無
- YEN-TING LIN 無
- 黃得瑞 無
- 黃信端 無
- 劉芳瑜 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Cheng-Ta Yang
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Locally advanced unresectable or metastatic HER2-overexpressing non-squamous non-small cell lung cancer
Objectives
The aim of this trial was to evaluate the efficacy and safety of trastuzumab deruxtecan combined with an immunotumor bispecific antibody versus standard care regimen of pembrolizumab combined with platinum-based doublet chemotherapy as 1L treatment in locally advanced, unresectable or metastatic, HER2-overexpressing, non-squamous non-small cell lung cancer.
Test Drug
Trastuzumab Deruxtecan(AZD4552 DS-8201A)
Active Ingredient
Trastuzumab Deruxtecan(AZD4552 DS-8201A)
Dosage Form
Injectable
Dosage
100mg
Endpoints
Sub-trial 1
1. Demonstrate the superiority of T-DXd plus rilvegostomig over pembrolizumab plus platinum-based doublet chemotherapy in subjects with unresectable locally advanced or metastatic non-squamous 1L, PD-L1 ≥ 1%, HER2-overexpressing NSCLC, through progression-free survival (PFS) assessed by a blinded independent central review committee (BICR).
2. Demonstrate the efficacy of T-DXd plus rilvegostomig over pembrolizumab plus platinum-based doublet chemotherapy in subjects with unresectable locally advanced or metastatic non-squamous 1L, PD-L1 ≥ 1%, HER2-overexpressing NSCLC, through overall survival (OS) assessment.
1. Demonstrate the superiority of T-DXd plus rilvegostomig over pembrolizumab plus platinum-based doublet chemotherapy in subjects with unresectable locally advanced or metastatic non-squamous 1L, PD-L1 ≥ 1%, HER2-overexpressing NSCLC, through progression-free survival (PFS) assessed by a blinded independent central review committee (BICR).
2. Demonstrate the efficacy of T-DXd plus rilvegostomig over pembrolizumab plus platinum-based doublet chemotherapy in subjects with unresectable locally advanced or metastatic non-squamous 1L, PD-L1 ≥ 1%, HER2-overexpressing NSCLC, through overall survival (OS) assessment.
Inclution Criteria
Subjects are eligible for this trial only if they meet all of the following criteria (and all criteria for each subtrial). However, if a specific subtrial criterion differs from the following primary criteria, the subtrial criterion shall apply.
Age
M-1. Subjects must be ≥ 18 years of age (or the legal consent age in the trial's jurisdiction) at the time of signing the ICF.
Subject Type and Disease Characteristics
M-2. Histological or cytological evidence of non-squamous NSCLC.
M-3. Treatment-naïve locally advanced unresectable or metastatic non-squamous NSCLC (unresectable stage III/IV as defined in the Joint Committee on Cancer Staging Manual, 9th edition).
M-4. World Health Organization (WHO) or East Coast Cancer Clinical Research Consortium (ECOG) performance status (PS) of 0 or 1.
M-5. Minimum life expectancy of 12 weeks.
M-6. Tumor specimens must be provided during pre-trial biomarker testing for HER2 IHC status assessment by a central reference laboratory. The HER2 positivity status of the tumor must be known prior to randomization. All subjects must be able to provide fresh tumor biopsies during screening or provide available tumor specimens collected within ≤ 3 months prior to screening for analysis. Subjects with inconclusive/unassessable results are ineligible for the trial.
M-7. Tumor PD-L1 status must be confirmed prior to randomization via one of the following methods:
(a) At a central laboratory designated by the trial commissioner, using the VENTANA PD-L1 (SP263) CDx assay.
(b) At a local laboratory certified by the trial commissioner, stratified and randomized based on local PD-L1 analysis results after the trial unit receives approval from the trial commissioner. Patients must also have acceptable tumor specimens available for testing at the central laboratory, as defined in Section 8, and compiled in the pathology manual and laboratory manual.
Note that only one tumor specimen is required to confirm HER2 IHC and PD-L1 status.
M-8. Testing performed according to local standard practice showed no record of tumor genomic variants for any other locally approved first-line (1L) targeted therapies available for use with any other active oncogenes (e.g., ROS1, NTRK, BRAF, RET, MET, etc.).
M-9. No known HER2 activating mutations.
M-10. No active EGFR mutations (including but not limited to exon 19 deletions or exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutations) and/or ALK recombinations. EGFR and ALK status must be known prior to randomization. Subjects with inconclusive/unevaluable results are ineligible for the trial.
Note: EGFR and ALK variant testing should be performed locally; if not, central laboratory testing is permitted. EGFR and/or ALK central laboratory test results obtained during screening in other Asperger's trials are permitted.
M-11. At least one measurable lesion as defined in RECIST version 1.1 (not previously treated with radiation, and accurately measured at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) with a longest diameter ≥ 10 mm [except for lymph nodes, whose short axis must be ≥ 15 mm], and capable of accurate repeatability).
M-12. Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days prior to randomization/enrollment.
M-13. Adequate organ and bone marrow function within 14 days prior to randomization
(Parameters for adequate organ and bone marrow function are listed in Table 4 below.) Note: No blood transfusions (red blood cells or platelets) or administration of granulocyte colony-stimulating factor (G-CSF) are permitted within 14 days prior to the day of bone marrow function assessment, or at any time after that date and before Day 1 of Cycle 1.
M-14. Adequate treatment clearance period prior to randomization, as defined in Table 5.
Weight
M-15. Weight at least 35 kg at screening and randomization.
Sexual Behavior and Contraception/Barrier Contraception Requirements
M-16. For sexual behavior and contraception/barrier contraception requirements for each subtrial, please refer to the trial plan for each subtrial.
Informed Consent
M-17. Ability to provide signed participant consent forms containing compliance with the requirements and limitations listed in the ICF and Clinical Trial Plan (CSP).
M-18. Before collecting specimens for the selective genetic research to support the Genomics Project, a signed and dated written consent form for the selective genetic research information must be provided.
Other Inclusion Criteria
M-19. All races, sexes, and ethnicities are eligible to participate in this trial.
Sub-Trial 1 Inclusion Criteria
In addition to the inclusion criteria in Section 5.1 of the main trial plan, participants assigned to Sub-Trial 1 must also meet all of the following criteria.
Participant Type and Disease Characteristics
SSI-1. The tumor PD-L1 TC performance is determined to be ≥ 1% by a central reference laboratory designated by the trial commissioner or a local laboratory deemed qualified by the trial commissioner (see Section 8.8.1.1 of the main trial plan for details). PD-L1 status must be known prior to randomization. Participants with PD-L1 TC < 1% or indeterminate/unevaluable outcomes are not eligible for the sub-trial.
SSI-2. Adequate organ and bone marrow function within 14 days prior to randomization (see Table 5 for additional parameters regarding appropriate organ and bone marrow function). Sexual Behavior and Contraception/Barrier Contraception Requirements
SSI-3. Males and females classified at birth, including all sex identities. The method of contraception used by the subject or their partner should comply with local regulations regarding contraception methods for clinical trial subjects. See below and Appendix A for further details.
a) Male Subjects:
From enrollment, throughout the trial period, until at least 4 months after the last dose of T-DXd, 180 days after the last dose of CTx, 60 days after the last dose of rilvegostomig, approximately 120 days (4 months) after the last dose of pembrolizumab, or the longer of the duration indicated on the relevant drug label for the marketed medication used in this trial, use condoms plus an additional method of contraception. The female partner of the male subject must use at least one highly effective method of contraception throughout this period. Not all methods of contraception are highly effective (see Appendix A for further details). If the subject's lifestyle is consistent with the overall duration of the clinical trial, then complete abstinence from heterosexual intercourse during the trial and drug clearance periods is an acceptable method of contraception. For unacceptable methods of contraception, please refer to Appendix A.
From enrollment, throughout the entire trial treatment period, and until at least 4 months after the last dose of T-DXd, 180 days after the last dose of CTx, 60 days after the last dose of rilvegostomig, or approximately 120 days (4 months) after the last dose of pembrolizumab, or the duration specified in the relevant drug manifest for the marketed product used in this trial, whichever is longer.
- From the first dose until at least 4 months after the last dose of T-DXd, 180 days after the last dose of CTx, 60 days after the last dose of rilvegostomig, or approximately 120 days (4 months) after the last dose of pembrolizumab, or the duration specified in the relevant drug manifest for the marketed product used in this trial, whichever is longer, male subjects should avoid freezing or donating sperm. Sperm preservation should be considered before inclusion in this trial.
b) Female subjects:
Infertile women, see Appendix A for definition.
Evidence of postmenopausal status, or a negative WOCBP serum pregnancy test result with an unsterilized male partner:
o For WOCBP, a negative serum pregnancy test result (with a sensitivity of at least 25 mIU/mL) must be obtained at the screening follow-up visit, and a urine β-HCG pregnancy test must be performed before each administration of the investigational drug (IP).
- Women currently receiving hormone replacement therapy (HRT) with an unclear postmenopausal status who wish to continue HRT during the trial must use a method of contraception suitable for WOCBP. Otherwise, HRT must be discontinued to allow confirmation of postmenopausal status before trial enrollment; see Appendix A for more details.
- From enrollment, throughout the entire trial period, until at least 7 months after the last dose of T-DXd, 180 days after the last dose of CTx, 60 days after the last dose of rilvegostomig, approximately 120 days (4 months) after the last dose of pembrolizumab, or the duration specified in the relevant drug's package insert for the marketed medication used in this trial, whichever is longer, WOCBP must use a highly effective method of contraception. Not all methods of contraception are highly effective (see Appendix A for further details). Throughout this period, unsterilized male partners of WOCBP must use male condoms in combination with spermicide. (Note: Male condoms should not be relied upon as the sole method of contraception.) If the subject's typical lifestyle is consistent with the overall length of the clinical trial, then complete abstinence from heterosexual intercourse during the trial and drug clearance periods is an acceptable method of contraception. For unacceptable methods of contraception, please refer to Appendix A.
From enrollment, throughout the entire trial period, until at least 7 months after the last dose of T-DXd, 180 days after the last dose of CTx, 60 days after the last dose of rilvegostomig, or approximately 120 days (4 months) after the last dose of pembrolizumab, or the duration specified in the relevant drug's package insert for the marketed drugs used in this trial, whichever is longer, subjects must not breastfeed and must not donate or retrieve eggs for their own use.
Age
M-1. Subjects must be ≥ 18 years of age (or the legal consent age in the trial's jurisdiction) at the time of signing the ICF.
Subject Type and Disease Characteristics
M-2. Histological or cytological evidence of non-squamous NSCLC.
M-3. Treatment-naïve locally advanced unresectable or metastatic non-squamous NSCLC (unresectable stage III/IV as defined in the Joint Committee on Cancer Staging Manual, 9th edition).
M-4. World Health Organization (WHO) or East Coast Cancer Clinical Research Consortium (ECOG) performance status (PS) of 0 or 1.
M-5. Minimum life expectancy of 12 weeks.
M-6. Tumor specimens must be provided during pre-trial biomarker testing for HER2 IHC status assessment by a central reference laboratory. The HER2 positivity status of the tumor must be known prior to randomization. All subjects must be able to provide fresh tumor biopsies during screening or provide available tumor specimens collected within ≤ 3 months prior to screening for analysis. Subjects with inconclusive/unassessable results are ineligible for the trial.
M-7. Tumor PD-L1 status must be confirmed prior to randomization via one of the following methods:
(a) At a central laboratory designated by the trial commissioner, using the VENTANA PD-L1 (SP263) CDx assay.
(b) At a local laboratory certified by the trial commissioner, stratified and randomized based on local PD-L1 analysis results after the trial unit receives approval from the trial commissioner. Patients must also have acceptable tumor specimens available for testing at the central laboratory, as defined in Section 8, and compiled in the pathology manual and laboratory manual.
Note that only one tumor specimen is required to confirm HER2 IHC and PD-L1 status.
M-8. Testing performed according to local standard practice showed no record of tumor genomic variants for any other locally approved first-line (1L) targeted therapies available for use with any other active oncogenes (e.g., ROS1, NTRK, BRAF, RET, MET, etc.).
M-9. No known HER2 activating mutations.
M-10. No active EGFR mutations (including but not limited to exon 19 deletions or exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutations) and/or ALK recombinations. EGFR and ALK status must be known prior to randomization. Subjects with inconclusive/unevaluable results are ineligible for the trial.
Note: EGFR and ALK variant testing should be performed locally; if not, central laboratory testing is permitted. EGFR and/or ALK central laboratory test results obtained during screening in other Asperger's trials are permitted.
M-11. At least one measurable lesion as defined in RECIST version 1.1 (not previously treated with radiation, and accurately measured at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) with a longest diameter ≥ 10 mm [except for lymph nodes, whose short axis must be ≥ 15 mm], and capable of accurate repeatability).
M-12. Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days prior to randomization/enrollment.
M-13. Adequate organ and bone marrow function within 14 days prior to randomization
(Parameters for adequate organ and bone marrow function are listed in Table 4 below.) Note: No blood transfusions (red blood cells or platelets) or administration of granulocyte colony-stimulating factor (G-CSF) are permitted within 14 days prior to the day of bone marrow function assessment, or at any time after that date and before Day 1 of Cycle 1.
M-14. Adequate treatment clearance period prior to randomization, as defined in Table 5.
Weight
M-15. Weight at least 35 kg at screening and randomization.
Sexual Behavior and Contraception/Barrier Contraception Requirements
M-16. For sexual behavior and contraception/barrier contraception requirements for each subtrial, please refer to the trial plan for each subtrial.
Informed Consent
M-17. Ability to provide signed participant consent forms containing compliance with the requirements and limitations listed in the ICF and Clinical Trial Plan (CSP).
M-18. Before collecting specimens for the selective genetic research to support the Genomics Project, a signed and dated written consent form for the selective genetic research information must be provided.
Other Inclusion Criteria
M-19. All races, sexes, and ethnicities are eligible to participate in this trial.
Sub-Trial 1 Inclusion Criteria
In addition to the inclusion criteria in Section 5.1 of the main trial plan, participants assigned to Sub-Trial 1 must also meet all of the following criteria.
Participant Type and Disease Characteristics
SSI-1. The tumor PD-L1 TC performance is determined to be ≥ 1% by a central reference laboratory designated by the trial commissioner or a local laboratory deemed qualified by the trial commissioner (see Section 8.8.1.1 of the main trial plan for details). PD-L1 status must be known prior to randomization. Participants with PD-L1 TC < 1% or indeterminate/unevaluable outcomes are not eligible for the sub-trial.
SSI-2. Adequate organ and bone marrow function within 14 days prior to randomization (see Table 5 for additional parameters regarding appropriate organ and bone marrow function). Sexual Behavior and Contraception/Barrier Contraception Requirements
SSI-3. Males and females classified at birth, including all sex identities. The method of contraception used by the subject or their partner should comply with local regulations regarding contraception methods for clinical trial subjects. See below and Appendix A for further details.
a) Male Subjects:
From enrollment, throughout the trial period, until at least 4 months after the last dose of T-DXd, 180 days after the last dose of CTx, 60 days after the last dose of rilvegostomig, approximately 120 days (4 months) after the last dose of pembrolizumab, or the longer of the duration indicated on the relevant drug label for the marketed medication used in this trial, use condoms plus an additional method of contraception. The female partner of the male subject must use at least one highly effective method of contraception throughout this period. Not all methods of contraception are highly effective (see Appendix A for further details). If the subject's lifestyle is consistent with the overall duration of the clinical trial, then complete abstinence from heterosexual intercourse during the trial and drug clearance periods is an acceptable method of contraception. For unacceptable methods of contraception, please refer to Appendix A.
From enrollment, throughout the entire trial treatment period, and until at least 4 months after the last dose of T-DXd, 180 days after the last dose of CTx, 60 days after the last dose of rilvegostomig, or approximately 120 days (4 months) after the last dose of pembrolizumab, or the duration specified in the relevant drug manifest for the marketed product used in this trial, whichever is longer.
- From the first dose until at least 4 months after the last dose of T-DXd, 180 days after the last dose of CTx, 60 days after the last dose of rilvegostomig, or approximately 120 days (4 months) after the last dose of pembrolizumab, or the duration specified in the relevant drug manifest for the marketed product used in this trial, whichever is longer, male subjects should avoid freezing or donating sperm. Sperm preservation should be considered before inclusion in this trial.
b) Female subjects:
Infertile women, see Appendix A for definition.
Evidence of postmenopausal status, or a negative WOCBP serum pregnancy test result with an unsterilized male partner:
o For WOCBP, a negative serum pregnancy test result (with a sensitivity of at least 25 mIU/mL) must be obtained at the screening follow-up visit, and a urine β-HCG pregnancy test must be performed before each administration of the investigational drug (IP).
- Women currently receiving hormone replacement therapy (HRT) with an unclear postmenopausal status who wish to continue HRT during the trial must use a method of contraception suitable for WOCBP. Otherwise, HRT must be discontinued to allow confirmation of postmenopausal status before trial enrollment; see Appendix A for more details.
- From enrollment, throughout the entire trial period, until at least 7 months after the last dose of T-DXd, 180 days after the last dose of CTx, 60 days after the last dose of rilvegostomig, approximately 120 days (4 months) after the last dose of pembrolizumab, or the duration specified in the relevant drug's package insert for the marketed medication used in this trial, whichever is longer, WOCBP must use a highly effective method of contraception. Not all methods of contraception are highly effective (see Appendix A for further details). Throughout this period, unsterilized male partners of WOCBP must use male condoms in combination with spermicide. (Note: Male condoms should not be relied upon as the sole method of contraception.) If the subject's typical lifestyle is consistent with the overall length of the clinical trial, then complete abstinence from heterosexual intercourse during the trial and drug clearance periods is an acceptable method of contraception. For unacceptable methods of contraception, please refer to Appendix A.
From enrollment, throughout the entire trial period, until at least 7 months after the last dose of T-DXd, 180 days after the last dose of CTx, 60 days after the last dose of rilvegostomig, or approximately 120 days (4 months) after the last dose of pembrolizumab, or the duration specified in the relevant drug's package insert for the marketed drugs used in this trial, whichever is longer, subjects must not breastfeed and must not donate or retrieve eggs for their own use.
Exclusion Criteria
Patients meeting any of the following criteria are ineligible for participation in the trial:
Medical Conditions
M-1. Mixed small cell lung cancer, squamous NSCLC, and sarcomatoid histological variant NSCLC.
M-2. Substance abuse or any other medical condition, such as a clinically significant cardiac or psychological condition, deemed by the trial administrator to potentially interfere with participation in the clinical trial or the assessment of trial outcomes.
M-3. Any spinal cord compression, leptomeningeal disease, or clinically active CNS metastases. Clinically active CNS metastases are defined as untreated, symptomatic, or requiring treatment with corticosteroids or antiepileptic drugs to control related symptoms.
Patients whose brain metastases are no longer symptomatic after treatment and do not require corticosteroids or antiepileptic drugs may be included in this trial if they have recovered from the acute toxicity of radiotherapy.
Patients receiving radiotherapy for CNS metastases must:
undergo stereotactic radiosurgery or Gamma Knife ≥ 7 days prior to randomization.
o. Whole-brain radiotherapy must be administered ≥ 14 days prior to randomization.
Patients with clinically inactive and untreated brain metastases may be included in the trial.
M-4. History of myocardial infarction (MI) and/or symptomatic congestive heart failure (CHF) (NYHA Class II–IV) within the 12 months prior to enrollment. Patients with troponin levels higher than the ULN (as defined by the manufacturer) at screening and without any MI-related symptoms should undergo cardiological consultation during screening to exclude MI.
M-5. Determined by the trial administrator:
a) Any evidence of disease (e.g., severe or uncontrolled systemic illness, including but not limited to persistent or active infection, cardiomyopathy of any etiology, symptomatic CHF [defined as NYHA > Class II], uncontrolled hypertension, unstable angina, history of MI within the past 12 months, severe chronic gastrointestinal disease with diarrhea, or mental illness/social status and/or active bleeding disorder), and/or
b) Active non-infectious skin disease requiring systemic treatment (including any grade of rash, urticaria, dermatitis, ulcers, or psoriasis), active or documented autoimmune or inflammatory disease requiring long-term steroid therapy or other immunosuppressive therapy; and/or
c) History of organ transplantation.
M-6. Ascites or pericardial effusion requiring drainage, peritoneal shunt, pleural-peritoneal shunt, or cell-free concentrated ascites reinfusion therapy (CART).
M-7. Lung Conditions:
a) Concurrent clinically significant lung-specific disease, including but not limited to any pre-existing lung disease (e.g., pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, etc., within 3 months prior to trial inclusion).
b) Documented history of any autoimmune, connective tissue, or inflammatory disease (e.g., rheumatoid arthritis, Scheringer's syndrome, sarcomatoid disease, etc.), or suspected lung involvement due to autoimmune disease at screening. Complete and detailed disease information should be documented in the eCRF for all enrolled subjects.
c) Previous lung resection (complete).
M-8. History of another primary malignancy, excluding:
a) Malignant tumors that have received curative treatment, with no known active disease for ≥ 2 years prior to the first dose of trial treatment and a low potential risk of recurrence.
b) Non-melanoma skin cancer treated appropriately and without evidence of disease.
c) Carcinoma in situ treated appropriately and without evidence of disease.
M-9. Evidence of the following infections:
a) Known active or uncontrolled hepatitis B or C infection at the time of screening – see Section 8.3.4 and Figure 3 for screening tests.
Patients with positive hepatitis C virus (HCV) antibodies are eligible only if their HCV RNA polymerase chain reaction (PCR) test result is negative.
Patients with hepatitis B are eligible if they meet the following criteria:
• Have been vaccinated against HBV, are anti-HBs positive only, and have no clinical signs of hepatitis.
• Are HBsAg negative and anti-HBc positive (i.e., have cleared HBV after infection), and meet the following criteria i-iii:
• Are HBsAg positive and have chronic HBV infection (lasting 6 months or longer), and meet the following criteria i-iii:
i. HBV DNA viral load < 100 IU/mL.
ii. Normal transaminase levels, or, if liver metastases are present, abnormal transaminase levels (AST/ALT < 3 × ULN and not caused by HBV infection).
iii. Antiviral therapy to be initiated or maintained as clinically necessary, as determined by the trial administrator.
Or
b) Active hepatitis A.
Or
c) Known poorly controlled HIV infection.
Goodly controlled HIV infection is defined as meeting all of the following criteria: undetectable viral RNA for 6 months, CD4+ count > 500 cells/μL, no history of acquired immunodeficiency syndrome (AIDS) (defined as CD4+ T cell count < 200 cells/μL, and/or opportunistic infection as defined by AIDS), and stable for at least 6 months using the same antiHIV medication.
Or
d) Open tuberculosis infection (clinical evaluation may include clinical history, physical examination, and radiographic abnormalities, or tuberculosis testing consistent with local practice).
M-10. Uncontrolled infection requiring treatment with intravenous (iv) antibiotics, antiviral drugs, or antifungal drugs.
M-11. History of primary active immunodeficiency.
M-12. Active or previously documented autoimmune or inflammatory disease, including inflammatory bowel disease (such as colitis or Crohn's disease), diverticulitis (excluding diverticulosis), systemic lupus erythematosus, sarcoidosis syndrome, Wegener's syndrome (granulomatous polyangiitis), Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, pneumonia (previous history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD), etc. Exceptions to this condition include:
a) Vitiligo or alopecia.
b) Patients with hypothyroidism (e.g., occurring after Hashimoto's syndrome) and stable on hormone replacement therapy.
c) Any chronic skin condition that does not require systemic treatment.
d) Patients without active disease in the 5 years prior to enrollment may be included in this trial.
M-13. History of steroid-induced (non-infectious) ILD/pneumonia (including radiation pneumonitis), current ILD/pneumonia, or suspected ILD/pneumonia that cannot be ruled out by imaging at screening.
M-14. Patients meeting one or more of the following criteria:
− Mean statically corrected QT interval prolongation > 470 ms on three repeated ECGs at screening.
− History of QT interval prolongation related to other medications requiring discontinuation of those medications.
− Congenital long QT syndrome, family history of long QT syndrome, or a first-degree relative who died suddenly under the age of 40 from an unexplained cause.
- A history of symptomatic or treatment-required (CTCAE grade 3) arrhythmias (multiple-discharge point extraventricular contractions, bigeminy, trigeminy, ventricular tachycardia); symptomatic or poorly controlled atrial fibrillation after treatment, or asymptomatic persistent ventricular tachycardia. Patients with pharmacologically controlled atrial fibrillation or pacemaker-controlled arrhythmias may be admitted to the trial based on the trial administrator's assessment (and a recommendation for consultation with a cardiologist).
M-15. Medical contraindications for platinum-based doublet chemotherapy (CTx): Previous/combination therapy
M-16. Prior systemic therapy (including but not limited to CTx, targeted therapy, anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT, or any other experimental immunotherapy) for advanced/metastatic non-squamous NSCLC.
Note: Eligibility is granted if the patient has previously received any adjuvant or lead adjuvant therapy other than chemotherapy drugs targeting topoisomerase I or HER2-targeted antibody anticancer therapies (including antibody-drug complexes [ADCs]), including immune checkpoint inhibitors [CPIs] [anti-PD-1/PD L1] or platinum-based regimens;
a) The last dose of adjuvant/lead adjuvant therapy was given at least 6 months prior to the date of the first dose of the investigational drug, and the disease has not relapsed or worsened on the date of the last dose of the investigational drug or within 12 months thereafter, and
b) The subject must not have experienced any toxicity that would have led to permanent discontinuation of previous immunotherapy.
M-18. Concurrently receiving any CTx, radiotherapy, experimental, biological, or hormonal therapy as cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy [HRT]) is permitted.
M-19. Previously received radiotherapy for locally advanced stage III unresectable NSCLC. M-20. Underwent major surgery (excluding vascular access placement) or major trauma within 4 weeks prior to the first dose of trial treatment, or is expected to undergo major surgery during the trial.
Note: Local surgery for a single lesion for palliative purposes is acceptable.
M-21. Has persistent toxicity (CTCAE grade ≥ 2) due to previous anticancer therapy, excluding hair loss. Inclusion may be granted if the trial administrator determines that irreversible toxicity (e.g., hearing loss) is reasonably expected not to worsen with trial treatment.
M-22. Received a live attenuated vaccine within 30 days prior to randomization (mRNA and replication-defective adenovirus vaccines are not considered live attenuated vaccines).
Note: Patients enrolled in the trial should not receive a live vaccine during the course of treatment with the investigational drug (IMP) until 30 days after the last dose of trial treatment.
M-23. Patients currently using or who have used immunosuppressive drugs within 14 days prior to randomization will be excluded. The following are exceptions to this condition:
a) Intranasal, inhaled, topical, or local steroid injections (e.g., intra-articular injections).
b) Steroids used as a precursor to an allergic reaction (e.g., a precursor to a CT scan, a precursor to CTx) or as a single-dose medication for palliative purposes (e.g., pain control).
M-24. Any concomitant medications known to be associated with torsades de pointes.
M-25. Herbal or natural products used for the treatment or prevention of any type of cancer that may interfere with the activity of the experimental treatment will be excluded.
1.5 Sub-trials 1 Exclusion Criteria
Please refer to Section 5.2 of the main trial plan.
Medical Conditions
M-1. Mixed small cell lung cancer, squamous NSCLC, and sarcomatoid histological variant NSCLC.
M-2. Substance abuse or any other medical condition, such as a clinically significant cardiac or psychological condition, deemed by the trial administrator to potentially interfere with participation in the clinical trial or the assessment of trial outcomes.
M-3. Any spinal cord compression, leptomeningeal disease, or clinically active CNS metastases. Clinically active CNS metastases are defined as untreated, symptomatic, or requiring treatment with corticosteroids or antiepileptic drugs to control related symptoms.
Patients whose brain metastases are no longer symptomatic after treatment and do not require corticosteroids or antiepileptic drugs may be included in this trial if they have recovered from the acute toxicity of radiotherapy.
Patients receiving radiotherapy for CNS metastases must:
undergo stereotactic radiosurgery or Gamma Knife ≥ 7 days prior to randomization.
o. Whole-brain radiotherapy must be administered ≥ 14 days prior to randomization.
Patients with clinically inactive and untreated brain metastases may be included in the trial.
M-4. History of myocardial infarction (MI) and/or symptomatic congestive heart failure (CHF) (NYHA Class II–IV) within the 12 months prior to enrollment. Patients with troponin levels higher than the ULN (as defined by the manufacturer) at screening and without any MI-related symptoms should undergo cardiological consultation during screening to exclude MI.
M-5. Determined by the trial administrator:
a) Any evidence of disease (e.g., severe or uncontrolled systemic illness, including but not limited to persistent or active infection, cardiomyopathy of any etiology, symptomatic CHF [defined as NYHA > Class II], uncontrolled hypertension, unstable angina, history of MI within the past 12 months, severe chronic gastrointestinal disease with diarrhea, or mental illness/social status and/or active bleeding disorder), and/or
b) Active non-infectious skin disease requiring systemic treatment (including any grade of rash, urticaria, dermatitis, ulcers, or psoriasis), active or documented autoimmune or inflammatory disease requiring long-term steroid therapy or other immunosuppressive therapy; and/or
c) History of organ transplantation.
M-6. Ascites or pericardial effusion requiring drainage, peritoneal shunt, pleural-peritoneal shunt, or cell-free concentrated ascites reinfusion therapy (CART).
M-7. Lung Conditions:
a) Concurrent clinically significant lung-specific disease, including but not limited to any pre-existing lung disease (e.g., pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, etc., within 3 months prior to trial inclusion).
b) Documented history of any autoimmune, connective tissue, or inflammatory disease (e.g., rheumatoid arthritis, Scheringer's syndrome, sarcomatoid disease, etc.), or suspected lung involvement due to autoimmune disease at screening. Complete and detailed disease information should be documented in the eCRF for all enrolled subjects.
c) Previous lung resection (complete).
M-8. History of another primary malignancy, excluding:
a) Malignant tumors that have received curative treatment, with no known active disease for ≥ 2 years prior to the first dose of trial treatment and a low potential risk of recurrence.
b) Non-melanoma skin cancer treated appropriately and without evidence of disease.
c) Carcinoma in situ treated appropriately and without evidence of disease.
M-9. Evidence of the following infections:
a) Known active or uncontrolled hepatitis B or C infection at the time of screening – see Section 8.3.4 and Figure 3 for screening tests.
Patients with positive hepatitis C virus (HCV) antibodies are eligible only if their HCV RNA polymerase chain reaction (PCR) test result is negative.
Patients with hepatitis B are eligible if they meet the following criteria:
• Have been vaccinated against HBV, are anti-HBs positive only, and have no clinical signs of hepatitis.
• Are HBsAg negative and anti-HBc positive (i.e., have cleared HBV after infection), and meet the following criteria i-iii:
• Are HBsAg positive and have chronic HBV infection (lasting 6 months or longer), and meet the following criteria i-iii:
i. HBV DNA viral load < 100 IU/mL.
ii. Normal transaminase levels, or, if liver metastases are present, abnormal transaminase levels (AST/ALT < 3 × ULN and not caused by HBV infection).
iii. Antiviral therapy to be initiated or maintained as clinically necessary, as determined by the trial administrator.
Or
b) Active hepatitis A.
Or
c) Known poorly controlled HIV infection.
Goodly controlled HIV infection is defined as meeting all of the following criteria: undetectable viral RNA for 6 months, CD4+ count > 500 cells/μL, no history of acquired immunodeficiency syndrome (AIDS) (defined as CD4+ T cell count < 200 cells/μL, and/or opportunistic infection as defined by AIDS), and stable for at least 6 months using the same antiHIV medication.
Or
d) Open tuberculosis infection (clinical evaluation may include clinical history, physical examination, and radiographic abnormalities, or tuberculosis testing consistent with local practice).
M-10. Uncontrolled infection requiring treatment with intravenous (iv) antibiotics, antiviral drugs, or antifungal drugs.
M-11. History of primary active immunodeficiency.
M-12. Active or previously documented autoimmune or inflammatory disease, including inflammatory bowel disease (such as colitis or Crohn's disease), diverticulitis (excluding diverticulosis), systemic lupus erythematosus, sarcoidosis syndrome, Wegener's syndrome (granulomatous polyangiitis), Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, pneumonia (previous history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD), etc. Exceptions to this condition include:
a) Vitiligo or alopecia.
b) Patients with hypothyroidism (e.g., occurring after Hashimoto's syndrome) and stable on hormone replacement therapy.
c) Any chronic skin condition that does not require systemic treatment.
d) Patients without active disease in the 5 years prior to enrollment may be included in this trial.
M-13. History of steroid-induced (non-infectious) ILD/pneumonia (including radiation pneumonitis), current ILD/pneumonia, or suspected ILD/pneumonia that cannot be ruled out by imaging at screening.
M-14. Patients meeting one or more of the following criteria:
− Mean statically corrected QT interval prolongation > 470 ms on three repeated ECGs at screening.
− History of QT interval prolongation related to other medications requiring discontinuation of those medications.
− Congenital long QT syndrome, family history of long QT syndrome, or a first-degree relative who died suddenly under the age of 40 from an unexplained cause.
- A history of symptomatic or treatment-required (CTCAE grade 3) arrhythmias (multiple-discharge point extraventricular contractions, bigeminy, trigeminy, ventricular tachycardia); symptomatic or poorly controlled atrial fibrillation after treatment, or asymptomatic persistent ventricular tachycardia. Patients with pharmacologically controlled atrial fibrillation or pacemaker-controlled arrhythmias may be admitted to the trial based on the trial administrator's assessment (and a recommendation for consultation with a cardiologist).
M-15. Medical contraindications for platinum-based doublet chemotherapy (CTx): Previous/combination therapy
M-16. Prior systemic therapy (including but not limited to CTx, targeted therapy, anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT, or any other experimental immunotherapy) for advanced/metastatic non-squamous NSCLC.
Note: Eligibility is granted if the patient has previously received any adjuvant or lead adjuvant therapy other than chemotherapy drugs targeting topoisomerase I or HER2-targeted antibody anticancer therapies (including antibody-drug complexes [ADCs]), including immune checkpoint inhibitors [CPIs] [anti-PD-1/PD L1] or platinum-based regimens;
a) The last dose of adjuvant/lead adjuvant therapy was given at least 6 months prior to the date of the first dose of the investigational drug, and the disease has not relapsed or worsened on the date of the last dose of the investigational drug or within 12 months thereafter, and
b) The subject must not have experienced any toxicity that would have led to permanent discontinuation of previous immunotherapy.
M-18. Concurrently receiving any CTx, radiotherapy, experimental, biological, or hormonal therapy as cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy [HRT]) is permitted.
M-19. Previously received radiotherapy for locally advanced stage III unresectable NSCLC. M-20. Underwent major surgery (excluding vascular access placement) or major trauma within 4 weeks prior to the first dose of trial treatment, or is expected to undergo major surgery during the trial.
Note: Local surgery for a single lesion for palliative purposes is acceptable.
M-21. Has persistent toxicity (CTCAE grade ≥ 2) due to previous anticancer therapy, excluding hair loss. Inclusion may be granted if the trial administrator determines that irreversible toxicity (e.g., hearing loss) is reasonably expected not to worsen with trial treatment.
M-22. Received a live attenuated vaccine within 30 days prior to randomization (mRNA and replication-defective adenovirus vaccines are not considered live attenuated vaccines).
Note: Patients enrolled in the trial should not receive a live vaccine during the course of treatment with the investigational drug (IMP) until 30 days after the last dose of trial treatment.
M-23. Patients currently using or who have used immunosuppressive drugs within 14 days prior to randomization will be excluded. The following are exceptions to this condition:
a) Intranasal, inhaled, topical, or local steroid injections (e.g., intra-articular injections).
b) Steroids used as a precursor to an allergic reaction (e.g., a precursor to a CT scan, a precursor to CTx) or as a single-dose medication for palliative purposes (e.g., pain control).
M-24. Any concomitant medications known to be associated with torsades de pointes.
M-25. Herbal or natural products used for the treatment or prevention of any type of cancer that may interfere with the activity of the experimental treatment will be excluded.
1.5 Sub-trials 1 Exclusion Criteria
Please refer to Section 5.2 of the main trial plan.
The Estimated Number of Participants
-
Taiwan
40 participants
-
Global
900 participants
