Brief Summary
This study will evaluate the efficacy, safety, and pharmacokinetics of DS-1062a versus docetaxel in participants with previously treated advanced or metastatic non-small cell lung cancer (NSCLC) with or without actionable genomic alterations.
Brief Title
Study of DS-1062a Versus Docetaxel in Previously Treated Advanced or Metastatic Non-small Cell Lung Cancer With or Without Actionable Genomic Alterations (TROPION-LUNG01)
Detailed Description
This study will evaluate DS-1062a 6.0 mg/kg vs docetaxel 75 mg/m\^2 in participants with advanced or metastatic NSCLC with or without actionable genomic alterations (AGAs). Participants without actionable genomic alterations must have been previously treated with platinum-based chemotherapy and α (anti)-programmed cell death 1 (PD-1)/α-programmed cell death ligand 1 (PD-L1) monoclonal antibody, either in combination or sequentially. Participants with AGA must have progressed on or after 1 platinum-containing therapy and 1 to 2 prior lines of approved targeted therapy for the applicable genomic alteration. The study will be divided into 3 periods: Screening Period, Treatment Period, and Follow-up Period.
Completion Date
Completion Date Type
Estimated
Conditions
Non-small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
Participants eligible for inclusion in the study must meet all inclusion criteria within 28 days of randomization into the study.
* Sign and date the inform consent form (ICF) prior to the start of any study specific qualification procedures.
* Adults ≥18 years (if the legal age of consent is \>18 years old, then follow local regulatory requirements)
* Life expectancy ≥3 months
* Has pathologically documented Stage IIIB, IIIC, or stage IV NSCLC disease with or without actionable genomic alterations (AGA) at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition) and meets following criteria for NSCLC:
* Participants without AGA:
1. Must have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK).
2. Must have no known genomic alterations in ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto oncogene B-raf (BRAF), mesenchymal-epithelial transition (MET) exon 14 skipping, or rearranged during transfection (RET).
* Participants with AGA must have one or more documented actionable genomic alteration(s): EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.
* Has documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC.
* Participant without AGA must meet 1 of the following prior therapy requirements for advanced or metastatic NSCLC:
1. Received platinum-based chemotherapy in combination with α-PD-1/α-PD-L1 monoclonal antibody as the only prior line of therapy.
* Includes participants who received prior platinum-based/chemotherapy with or without radiotherapy with maintenance α-PD-1/α-PD-L1 monoclonal antibody for Stage III disease and relapsed/progressed within 6 months from the last dose of platinum-based chemotherapy.
* Includes participants who received prior platinum-based/chemotherapy with or without radiotherapy (with or without maintenance α-PD-1/α-PD-L1 monoclonal antibody) for Stage III disease and subsequently received α-PD-1/α-PD-L1 monoclonal antibody therapy (with or without platinum-based chemotherapy) for recurrent disease.
2. Received platinum-based chemotherapy and α-PD-1/α-PD-L1 monoclonal antibody (in either order) sequentially as the only 2 prior lines of therapy.
* Participants with AGA must meet the following for advanced or metastatic NSCLC:
1. Participants who have been treated with 1 or 2 prior lines of applicable targeted therapy that is locally approved for the participant's genomic alteration at the time of screening;
* Participants who have tumors with EGFR L858R or exon 19 deletion mutations must have received prior Osimertinib.
* Those who received a targeted agent as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of targeted therapy for the same genomic alteration (which may or may not be same agent used in the adjuvant setting) for relapsed/progressive disease.
* Participants who have been treated with a prior tyrosine kinase inhibitor (TKI ) must receive additional approved targeted therapy, if locally available and clinically appropriate, for the applicable genomic alteration, or the participant will not be allowed in the study.
2. Participants who have received platinum-based chemotherapy as the only prior line of cytotoxic therapy:
* One platinum-containing regimen for advanced disease
* Those who received a platinum-containing regimen as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of platinum-containing therapy (which may or may not be same as in the adjuvant setting) for relapsed/progressive disease.
3. May have received up to one α-PD-1/α-PD-L1 monoclonal antibody alone or in combination with a cytotoxic agent.
* Must undergo a pre-treatment tumor biopsy procedure or if available, tumor tissue previously retrieved from a biopsy procedure performed within 2 years prior to the participant signing informed consent and that has a minimum of 10 × 4 micron sections or a tissue block equivalent of 10 × 4 micron sections may be substituted for the pre-treatment biopsy procedure during Screening. If a documented law or regulation prohibits (or does not approve) sample collection, then such samples will not be collected/submitted
* Measurable disease based on local imaging assessment using RECIST v1.1
* Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening
* Within 7 days before randomization, has adequate bone marrow, hepatic, and renal function
* Left ventricular ejection fraction (LVEF) ≥50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization
* Adequate blood clotting function defined as international normalized ratio/prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤1.5 × upper limit of normal (ULN)
* Adequate treatment washout period before randomization
* Females of childbearing potential must have a negative serum pregnancy test at screening and must be willing to use highly effective birth control from the time of enrollment up to 7 months after the last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
* Males must be surgically sterile or must use a condom in addition to highly effective birth control if his partners are of reproductive potential from the time of enrollment and for at least 4 months after last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
* Male participants must not freeze or donate sperm from the time of Screening and throughout the study period and for at least 4 months after the last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
* Female participants must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study period and for at least 7 months after the last dose of DS-1062a and for at least 6 months after the last dose of docetaxel
Exclusion Criteria:
* Mixed small-cell lung cancer (SCLC) and NSCLC histology
* Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases who are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy.
* Has leptomeningeal carcinomatosis or metastasis
* Had prior treatment with:
* Any agent including antibody drug conjugate (ADC) containing a chemotherapeutic agent targeting topoisomerase I
* TROP2-targeted therapy
* Docetaxel
* Had prior treatment with platinum-based chemotherapy and prior immunotherapy for Stage II NSCLC disease (eg, in the neo-adjuvant or adjuvant setting) without subsequently meeting the prior therapy requirements for Stage III or metastatic NSCLC disease
* Has NSCLC disease that is eligible for definitive local therapy alone
* Has uncontrolled or significant cardiac disease, including:
* Mean QT interval corrected for heart rate using Fridericia's formula \>470 msec (based on the average of Screening triplicate 12-lead electrocardiogram \[ECG\] determinations).
* Myocardial infarction or uncontrolled/unstable angina within 6 months before randomization
* Congestive heart failure (CHF) (New York Heart Association Class II to IV) at Screening. Participants with a history of Class II to IV CHF prior to Screening, must have returned to Class I CHF and have LVEF ≥50% (by either an ECHO or MUGA scan within 28 days before randomization) in order to be eligible.
* Uncontrolled or significant cardiac arrhythmia
* LVEF \<50% by ECHO or MUGA scan within 28 days before randomization
* Uncontrolled hypertension (resting systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg) within 28 days before randomization
* Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening
* Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months before randomization, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.), or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.
* Significant third-space fluid retention (for example ascites or pleural effusion) and is not amenable for required repeated drainage
* Clinically significant corneal disease
* Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections
* Has known human immunodeficiency virus (HIV) infection that is not well controlled
* Has an active or uncontrolled hepatitis B and/or hepatitis C infection, is positive for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (hepatitis B surface antigen \[HBsAg\], anti-hepatitis B surface antibody \[anti-HBs\], anti-hepatitis B core antibody \[anti-HBc\], or hepatitis B virus \[HBV\] DNA), and/or hepatitis C infection (as per hepatitis C virus \[HCV\] RNA) within 28 days of randomization.
* Has a history of malignancy, other than NSCLC, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years
* Toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet improved to NCI-CTCAE version 5.0 Grade ≤1 or baseline
* Has a history of severe hypersensitivity reactions to either the drug substances, inactive ingredients (including but not limited to polysorbate 80) of DS-1062a or docetaxel, or monoclonal antibodies
* Pregnant or breastfeeding
* Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions
Participants eligible for inclusion in the study must meet all inclusion criteria within 28 days of randomization into the study.
* Sign and date the inform consent form (ICF) prior to the start of any study specific qualification procedures.
* Adults ≥18 years (if the legal age of consent is \>18 years old, then follow local regulatory requirements)
* Life expectancy ≥3 months
* Has pathologically documented Stage IIIB, IIIC, or stage IV NSCLC disease with or without actionable genomic alterations (AGA) at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition) and meets following criteria for NSCLC:
* Participants without AGA:
1. Must have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK).
2. Must have no known genomic alterations in ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto oncogene B-raf (BRAF), mesenchymal-epithelial transition (MET) exon 14 skipping, or rearranged during transfection (RET).
* Participants with AGA must have one or more documented actionable genomic alteration(s): EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.
* Has documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC.
* Participant without AGA must meet 1 of the following prior therapy requirements for advanced or metastatic NSCLC:
1. Received platinum-based chemotherapy in combination with α-PD-1/α-PD-L1 monoclonal antibody as the only prior line of therapy.
* Includes participants who received prior platinum-based/chemotherapy with or without radiotherapy with maintenance α-PD-1/α-PD-L1 monoclonal antibody for Stage III disease and relapsed/progressed within 6 months from the last dose of platinum-based chemotherapy.
* Includes participants who received prior platinum-based/chemotherapy with or without radiotherapy (with or without maintenance α-PD-1/α-PD-L1 monoclonal antibody) for Stage III disease and subsequently received α-PD-1/α-PD-L1 monoclonal antibody therapy (with or without platinum-based chemotherapy) for recurrent disease.
2. Received platinum-based chemotherapy and α-PD-1/α-PD-L1 monoclonal antibody (in either order) sequentially as the only 2 prior lines of therapy.
* Participants with AGA must meet the following for advanced or metastatic NSCLC:
1. Participants who have been treated with 1 or 2 prior lines of applicable targeted therapy that is locally approved for the participant's genomic alteration at the time of screening;
* Participants who have tumors with EGFR L858R or exon 19 deletion mutations must have received prior Osimertinib.
* Those who received a targeted agent as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of targeted therapy for the same genomic alteration (which may or may not be same agent used in the adjuvant setting) for relapsed/progressive disease.
* Participants who have been treated with a prior tyrosine kinase inhibitor (TKI ) must receive additional approved targeted therapy, if locally available and clinically appropriate, for the applicable genomic alteration, or the participant will not be allowed in the study.
2. Participants who have received platinum-based chemotherapy as the only prior line of cytotoxic therapy:
* One platinum-containing regimen for advanced disease
* Those who received a platinum-containing regimen as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of platinum-containing therapy (which may or may not be same as in the adjuvant setting) for relapsed/progressive disease.
3. May have received up to one α-PD-1/α-PD-L1 monoclonal antibody alone or in combination with a cytotoxic agent.
* Must undergo a pre-treatment tumor biopsy procedure or if available, tumor tissue previously retrieved from a biopsy procedure performed within 2 years prior to the participant signing informed consent and that has a minimum of 10 × 4 micron sections or a tissue block equivalent of 10 × 4 micron sections may be substituted for the pre-treatment biopsy procedure during Screening. If a documented law or regulation prohibits (or does not approve) sample collection, then such samples will not be collected/submitted
* Measurable disease based on local imaging assessment using RECIST v1.1
* Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening
* Within 7 days before randomization, has adequate bone marrow, hepatic, and renal function
* Left ventricular ejection fraction (LVEF) ≥50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization
* Adequate blood clotting function defined as international normalized ratio/prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤1.5 × upper limit of normal (ULN)
* Adequate treatment washout period before randomization
* Females of childbearing potential must have a negative serum pregnancy test at screening and must be willing to use highly effective birth control from the time of enrollment up to 7 months after the last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
* Males must be surgically sterile or must use a condom in addition to highly effective birth control if his partners are of reproductive potential from the time of enrollment and for at least 4 months after last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
* Male participants must not freeze or donate sperm from the time of Screening and throughout the study period and for at least 4 months after the last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
* Female participants must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study period and for at least 7 months after the last dose of DS-1062a and for at least 6 months after the last dose of docetaxel
Exclusion Criteria:
* Mixed small-cell lung cancer (SCLC) and NSCLC histology
* Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases who are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy.
* Has leptomeningeal carcinomatosis or metastasis
* Had prior treatment with:
* Any agent including antibody drug conjugate (ADC) containing a chemotherapeutic agent targeting topoisomerase I
* TROP2-targeted therapy
* Docetaxel
* Had prior treatment with platinum-based chemotherapy and prior immunotherapy for Stage II NSCLC disease (eg, in the neo-adjuvant or adjuvant setting) without subsequently meeting the prior therapy requirements for Stage III or metastatic NSCLC disease
* Has NSCLC disease that is eligible for definitive local therapy alone
* Has uncontrolled or significant cardiac disease, including:
* Mean QT interval corrected for heart rate using Fridericia's formula \>470 msec (based on the average of Screening triplicate 12-lead electrocardiogram \[ECG\] determinations).
* Myocardial infarction or uncontrolled/unstable angina within 6 months before randomization
* Congestive heart failure (CHF) (New York Heart Association Class II to IV) at Screening. Participants with a history of Class II to IV CHF prior to Screening, must have returned to Class I CHF and have LVEF ≥50% (by either an ECHO or MUGA scan within 28 days before randomization) in order to be eligible.
* Uncontrolled or significant cardiac arrhythmia
* LVEF \<50% by ECHO or MUGA scan within 28 days before randomization
* Uncontrolled hypertension (resting systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg) within 28 days before randomization
* Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening
* Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months before randomization, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.), or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.
* Significant third-space fluid retention (for example ascites or pleural effusion) and is not amenable for required repeated drainage
* Clinically significant corneal disease
* Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections
* Has known human immunodeficiency virus (HIV) infection that is not well controlled
* Has an active or uncontrolled hepatitis B and/or hepatitis C infection, is positive for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (hepatitis B surface antigen \[HBsAg\], anti-hepatitis B surface antibody \[anti-HBs\], anti-hepatitis B core antibody \[anti-HBc\], or hepatitis B virus \[HBV\] DNA), and/or hepatitis C infection (as per hepatitis C virus \[HCV\] RNA) within 28 days of randomization.
* Has a history of malignancy, other than NSCLC, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years
* Toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet improved to NCI-CTCAE version 5.0 Grade ≤1 or baseline
* Has a history of severe hypersensitivity reactions to either the drug substances, inactive ingredients (including but not limited to polysorbate 80) of DS-1062a or docetaxel, or monoclonal antibodies
* Pregnant or breastfeeding
* Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions
Inclusion Criteria
Inclusion Criteria:
Participants eligible for inclusion in the study must meet all inclusion criteria within 28 days of randomization into the study.
* Sign and date the inform consent form (ICF) prior to the start of any study specific qualification procedures.
* Adults ≥18 years (if the legal age of consent is \>18 years old, then follow local regulatory requirements)
* Life expectancy ≥3 months
* Has pathologically documented Stage IIIB, IIIC, or stage IV NSCLC disease with or without actionable genomic alterations (AGA) at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition) and meets following criteria for NSCLC:
* Participants without AGA:
1. Must have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK).
2. Must have no known genomic alterations in ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto oncogene B-raf (BRAF), mesenchymal-epithelial transition (MET) exon 14 skipping, or rearranged during transfection (RET).
* Participants with AGA must have one or more documented actionable genomic alteration(s): EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.
* Has documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC.
* Participant without AGA must meet 1 of the following prior therapy requirements for advanced or metastatic NSCLC:
1. Received platinum-based chemotherapy in combination with α-PD-1/α-PD-L1 monoclonal antibody as the only prior line of therapy.
* Includes participants who received prior platinum-based/chemotherapy with or without radiotherapy with maintenance α-PD-1/α-PD-L1 monoclonal antibody for Stage III disease and relapsed/progressed within 6 months from the last dose of platinum-based chemotherapy.
* Includes participants who received prior platinum-based/chemotherapy with or without radiotherapy (with or without maintenance α-PD-1/α-PD-L1 monoclonal antibody) for Stage III disease and subsequently received α-PD-1/α-PD-L1 monoclonal antibody therapy (with or without platinum-based chemotherapy) for recurrent disease.
2. Received platinum-based chemotherapy and α-PD-1/α-PD-L1 monoclonal antibody (in either order) sequentially as the only 2 prior lines of therapy.
* Participants with AGA must meet the following for advanced or metastatic NSCLC:
1. Participants who have been treated with 1 or 2 prior lines of applicable targeted therapy that is locally approved for the participant's genomic alteration at the time of screening;
* Participants who have tumors with EGFR L858R or exon 19 deletion mutations must have received prior Osimertinib.
* Those who received a targeted agent as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of targeted therapy for the same genomic alteration (which may or may not be same agent used in the adjuvant setting) for relapsed/progressive disease.
* Participants who have been treated with a prior tyrosine kinase inhibitor (TKI ) must receive additional approved targeted therapy, if locally available and clinically appropriate, for the applicable genomic alteration, or the participant will not be allowed in the study.
2. Participants who have received platinum-based chemotherapy as the only prior line of cytotoxic therapy:
* One platinum-containing regimen for advanced disease
* Those who received a platinum-containing regimen as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of platinum-containing therapy (which may or may not be same as in the adjuvant setting) for relapsed/progressive disease.
3. May have received up to one α-PD-1/α-PD-L1 monoclonal antibody alone or in combination with a cytotoxic agent.
* Must undergo a pre-treatment tumor biopsy procedure or if available, tumor tissue previously retrieved from a biopsy procedure performed within 2 years prior to the participant signing informed consent and that has a minimum of 10 × 4 micron sections or a tissue block equivalent of 10 × 4 micron sections may be substituted for the pre-treatment biopsy procedure during Screening. If a documented law or regulation prohibits (or does not approve) sample collection, then such samples will not be collected/submitted
* Measurable disease based on local imaging assessment using RECIST v1.1
* Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening
* Within 7 days before randomization, has adequate bone marrow, hepatic, and renal function
* Left ventricular ejection fraction (LVEF) ≥50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization
* Adequate blood clotting function defined as international normalized ratio/prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤1.5 × upper limit of normal (ULN)
* Adequate treatment washout period before randomization
* Females of childbearing potential must have a negative serum pregnancy test at screening and must be willing to use highly effective birth control from the time of enrollment up to 7 months after the last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
* Males must be surgically sterile or must use a condom in addition to highly effective birth control if his partners are of reproductive potential from the time of enrollment and for at least 4 months after last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
* Male participants must not freeze or donate sperm from the time of Screening and throughout the study period and for at least 4 months after the last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
* Female participants must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study period and for at least 7 months after the last dose of DS-1062a and for at least 6 months after the last dose of docetaxel
Participants eligible for inclusion in the study must meet all inclusion criteria within 28 days of randomization into the study.
* Sign and date the inform consent form (ICF) prior to the start of any study specific qualification procedures.
* Adults ≥18 years (if the legal age of consent is \>18 years old, then follow local regulatory requirements)
* Life expectancy ≥3 months
* Has pathologically documented Stage IIIB, IIIC, or stage IV NSCLC disease with or without actionable genomic alterations (AGA) at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition) and meets following criteria for NSCLC:
* Participants without AGA:
1. Must have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK).
2. Must have no known genomic alterations in ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto oncogene B-raf (BRAF), mesenchymal-epithelial transition (MET) exon 14 skipping, or rearranged during transfection (RET).
* Participants with AGA must have one or more documented actionable genomic alteration(s): EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.
* Has documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC.
* Participant without AGA must meet 1 of the following prior therapy requirements for advanced or metastatic NSCLC:
1. Received platinum-based chemotherapy in combination with α-PD-1/α-PD-L1 monoclonal antibody as the only prior line of therapy.
* Includes participants who received prior platinum-based/chemotherapy with or without radiotherapy with maintenance α-PD-1/α-PD-L1 monoclonal antibody for Stage III disease and relapsed/progressed within 6 months from the last dose of platinum-based chemotherapy.
* Includes participants who received prior platinum-based/chemotherapy with or without radiotherapy (with or without maintenance α-PD-1/α-PD-L1 monoclonal antibody) for Stage III disease and subsequently received α-PD-1/α-PD-L1 monoclonal antibody therapy (with or without platinum-based chemotherapy) for recurrent disease.
2. Received platinum-based chemotherapy and α-PD-1/α-PD-L1 monoclonal antibody (in either order) sequentially as the only 2 prior lines of therapy.
* Participants with AGA must meet the following for advanced or metastatic NSCLC:
1. Participants who have been treated with 1 or 2 prior lines of applicable targeted therapy that is locally approved for the participant's genomic alteration at the time of screening;
* Participants who have tumors with EGFR L858R or exon 19 deletion mutations must have received prior Osimertinib.
* Those who received a targeted agent as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of targeted therapy for the same genomic alteration (which may or may not be same agent used in the adjuvant setting) for relapsed/progressive disease.
* Participants who have been treated with a prior tyrosine kinase inhibitor (TKI ) must receive additional approved targeted therapy, if locally available and clinically appropriate, for the applicable genomic alteration, or the participant will not be allowed in the study.
2. Participants who have received platinum-based chemotherapy as the only prior line of cytotoxic therapy:
* One platinum-containing regimen for advanced disease
* Those who received a platinum-containing regimen as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of platinum-containing therapy (which may or may not be same as in the adjuvant setting) for relapsed/progressive disease.
3. May have received up to one α-PD-1/α-PD-L1 monoclonal antibody alone or in combination with a cytotoxic agent.
* Must undergo a pre-treatment tumor biopsy procedure or if available, tumor tissue previously retrieved from a biopsy procedure performed within 2 years prior to the participant signing informed consent and that has a minimum of 10 × 4 micron sections or a tissue block equivalent of 10 × 4 micron sections may be substituted for the pre-treatment biopsy procedure during Screening. If a documented law or regulation prohibits (or does not approve) sample collection, then such samples will not be collected/submitted
* Measurable disease based on local imaging assessment using RECIST v1.1
* Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening
* Within 7 days before randomization, has adequate bone marrow, hepatic, and renal function
* Left ventricular ejection fraction (LVEF) ≥50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization
* Adequate blood clotting function defined as international normalized ratio/prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤1.5 × upper limit of normal (ULN)
* Adequate treatment washout period before randomization
* Females of childbearing potential must have a negative serum pregnancy test at screening and must be willing to use highly effective birth control from the time of enrollment up to 7 months after the last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
* Males must be surgically sterile or must use a condom in addition to highly effective birth control if his partners are of reproductive potential from the time of enrollment and for at least 4 months after last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
* Male participants must not freeze or donate sperm from the time of Screening and throughout the study period and for at least 4 months after the last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
* Female participants must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study period and for at least 7 months after the last dose of DS-1062a and for at least 6 months after the last dose of docetaxel
Gender
All
Gender Based
false
Keywords
Metastatic Non-small Cell Lung Cancer
Advanced Non-small Cell Lung Cancer
Non-small Cell Lung Cancer
DS-1062
Docetaxel
Datopotamab Deruxtecan (Dato-DXd)
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04656652
Org Class
Industry
Org Full Name
Daiichi Sankyo
Org Study Id
DS1062-A-U301
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Phase 3 Randomized Study of DS-1062a Versus Docetaxel in Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-LUNG01)
Primary Outcomes
Outcome Description
PFS is defined as the time from randomization to the earlier of the dates of the first documentation of radiographic progressive disease or death due to any cause.
Outcome Measure
Progression-free Survival (PFS) As Assessed by Blinded Independent Central Review (BICR) Per RECIST v1.1 Following DS-1062a Versus Docetaxel
Outcome Time Frame
From randomization until disease progression or death (whichever occurs first), up to approximately 27 months
Outcome Description
OS is defined as the time from randomization to the date of death due to any cause.
Outcome Measure
Overall Survival (OS) Following DS-1062a Versus Docetaxel
Outcome Time Frame
From randomization until date of death due to any cause, up to to approximately 38 months
Secondary Ids
Secondary Id
2020-004643-80
Secondary Id
2023-509865-19-00
Secondary Outcomes
Outcome Description
PFS is defined as the time from randomization to the earlier of the dates of the first documentation of radiographic progressive disease or death due to any cause.
Outcome Time Frame
From randomization until disease progression or death (whichever occurs first), up to approximately 43 months
Outcome Measure
Progression-free Survival (PFS) As Assessed by Investigator Per RECIST v1.1 Following DS-1062a Versus Docetaxel
Outcome Description
ORR is defined as the proportion of subjects who achieved a best overall response (BOR) of complete response (CR) or partial response (PR), as assessed by BICR and investigator per RECIST v1.1.
Outcome Time Frame
From randomization until disease progression or death (whichever occurs first), up to approximately 43 months
Outcome Measure
Objective Response Rate (ORR) As Assessed by Blinded Independent Central Review (BICR) and Investigator As Per RECIST v1.1 Following DS-1062a Versus Docetaxel
Outcome Description
DOR is defined as the time from the date of the first documentation of objective response (confirmed CR or confirmed PR) to the date of the first documentation of radiographic Progressive Disease or death due to any cause, whichever occurs first.
Outcome Time Frame
From date of first objective response (CR or PR) to date of first radiographic disease progression or death due to any cause (whichever occurs first), up to approximately 43 months
Outcome Measure
Duration of Response (DOR) As Assessed by Blinded Independent Central Review (BICR) and Investigator As Per RECIST v1.1 Following DS-1062a Versus Docetaxel
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
CARCINOMA, NON-SMALL-CELL LUNG
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
LUNG NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
DOCETAXEL
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
ORGANIC CHEMICALS
DITERPENES
TERPENES