A Phase 3, Randomized, Open Label Study of Patritumab Deruxtecan Versus Platinum based Chemotherapy in Metastatic or Locally Advanced Epidermal Growth Factor Receptor-mutated (EGFRm) Non small Cell Lung Cancer (NSCLC) After Failure of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) Therapy (HERTHENA-Lung02)
A Study of Patritumab Deruxtecan Versus Platinum-based Chemotherapy in Metastatic or Locally Advanced EGFRm NSCLC After Failure of EGFR TKI Therapy
Inoguchi Akihiro
DAIICHI SANKYO Co.,Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial@daiichisankyo.co.jp
Contact for Clinical Trial Information
DAIICHI SANKYO Co.,Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial@daiichisankyo.co.jp
Not Recruiting
May. 31, 2022
July. 08, 2022
560
Interventional
randomized controlled trial
open(masking not used)
active control
parallel assignment
treatment purpose
1. Is a male or female subject aged >=18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
2. Has histologically or cytologically documented metastatic or locally advanced non-squamous NSCLC not amenable to curative surgery or radiation.
3. Has documentation of an EGFR-activating mutation detected from tumor tissue or blood sample: exon 19 deletion or L858R at diagnosis or thereafter.
4. Received 1 or 2 prior line(s) of an approved EGFR TKI treatment in the metastatic or locally advanced setting, which must include a third - generation EGFR TKI.
5. May have received either neoadjuvant and/or adjuvant treatment if progression to metastatic or locally advanced disease occurred at least 12 months after the last dose of such therapy and subsequently experienced disease progression on or after third-generation EGFR TKI treatment administered in the metastatic or locally advanced setting.
6. Has not received any other prior systemic therapies in the metastatic or locally advanced setting (including chemotherapy, immunotherapy etc) (even if administered in combination with EGFR TKI).
7. Has documentation of radiographic disease progression while receiving or after receiving a third generation EGFR TKI for metastatic or locally advanced disease.
8. Has at least 1 measurable lesion as per RECIST v1.1 by Investigator assessment.
9. Is willing to have a tumor biopsy or provide recently obtained tumor tissue.
10. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening.
11. Has adequate bone marrow reserve and organ function based on local laboratory evaluation within 14 days prior to randomization:
- Platelet count: >=100,000/mm^3 or >=100 x 10^9/L
- Absolute neutrophil count: >=1500/mm^3 or >=1.5 x 10^9/L
- Hemoglobin (Hgb): >=9.0 g/dL
- Creatine clearance (CrCl): CrCl >=45 mL/min calculated by using the Cockcroft-Gault equation or measured CrCl
- Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT): AST/ALT <=3 x Upper limit of normal (ULN)
- Total bilirubin (TBL): TBL <=1.5 x ULN
- Serum albumin: >=2.5 g/dL
- Prothrombin time (PT) or Prothrombin time-International normalized ratio (PT-INR) and activated partial thromboplastin time (aPTT)/ partial thromboplastin time (PTT): <=1.5 x ULN, except for participants receiving coumarin-derivative anticoagulants or other similar anticoagulant therapy who must have PT-INR within therapeutic range as deemed appropriate by the Investigator
1. Has any previous histologic or cytologic evidence of small cell OR combined small cell/non-small cell disease in the archival tumor tissue or pretreatment tumor biopsy, or squamous NSCLC histology
2. Has any history of interstitial lung disease (ILD) (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during Screening
3. Has clinically severe respiratory compromise (based on the Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to the following:
- Any underlying pulmonary disorder, restrictive lung disease, or pleural effusion
- Any autoimmune, connective tissue, or inflammatory disorders where there is documented, or a suspicion of pulmonary involvement at the time of Screening
- OR prior complete pneumonectomy
4. Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to randomization
5. Has evidence of any leptomeningeal disease
6. Has evidence of clinically active spinal cord compression or brain metastases, defined as being symptomatic and untreated, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
7. Any prior treatment with any agent including an antibody drug conjugate (ADC) containing a chemotherapeutic agent targeting topoisomerase I, human epidermal growth factor receptor 3 (HER3) antibody, and any systemic therapies (other than EGFR TKIs) in the metastatic/locally advanced setting, including chemotherapy or any other systemic therapy in combination with an EGFR TKI
8. Has history of other active malignancy within 3 years prior to randomization, except for adequately resected nonmelanoma skin cancer, adequately treated intraepithelial carcinoma of the cervix, and any other curatively treated in situ disease
9. Has uncontrolled or significant cardiovascular disease prior to randomization
10. Has active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of active viral infection within 28 days of randomization
11. Has a known human immunodeficiency virus (HIV) infection that is not well controlled
12. Has clinically significant corneal disease
18age old over
No limit
Both
Metastatic or locally advanced nonsquamous NSCLC with an EGFR-activating mutation
ARM 1:
- Intravenous, Patritumab deruxtecan 5.6 mg/kg every 3 weeks (q3W)
ARM 2:
- Intravenous, Platinum based chemotherapy for 4 cycles: pemetrexed plus either cisplatin or carboplatin (target area under the curve 5 [AUC5] by using the Calvert formula) q3W. Participants without disease progression after 4 cycles of platinum plus pemetrexed therapy may continue treatment with maintenance pemetrexed with no restriction on the number of cycles.
Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review Based on RECIST v1.1
Progression-free survival (PFS) is defined as the time from the date of randomization to the earlier of the dates of the first documentation of objective progression of disease or death due to any cause.
[Time Frame: Baseline up to approximately 49 months]
1. Overall Survival (OS)
Overall survival (OS) is defined as the time from the date of randomization to the date of death due to any cause.
[Time Frame: Baseline up to approximately 49 months]
2. Progression-free Survival (PFS) as Assessed by Investigator Review Based on RECIST v1.1
Progression-free survival (PFS) is defined as the time from the date of randomization to the earlier of the dates of the first documentation of objective progression of disease or death due to any cause.
[Time Frame: Baseline up to approximately 49 months]
3. Progression-free Survival on the next line of therapy (PFS2) as Assessed by Local Standard Clinical Practice Progression-free survival on the next line of therapy (PFS2)by local standard clinical practice is defined as the time from date of randomization to the documented progression on the first new anticancer therapy (if administered) or death due to any cause, whichever occurred first.
[Time Frame: Baseline up to approximately 49 months]
4. Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review and Investigator Review Based on RECIST v1.1
Objective response rate (ORR) is defined as the proportion of participants who have a confirmed best overall response (BOR) of complete response (CR) or partial response (PR).
[Time Frame: Baseline up to approximately 49 months]
5. Duration of Response (DoR) as Assessed by Blinded Independent Central Review and Investigator Review Based on RECIST v1.1
Duration of response (DoR) is defined as the time from the first documentation of objective response (CR or PR) to the earlier of the dates of the first documentation of objective progression of disease or death due to any cause.
[Time Frame: Baseline up to approximately 49 months]
6. Clinical Benefit Rate (CBR) as Assessed by Blinded Independent Central Review and Investigator Review Based on RECIST v1.1
Clinical benefit rate (CBR) will be assessed by blinded independent central review and Investigator based on RECIST v1.1. CBR is defined as the proportion of participants who have a confirmed BOR of CR, PR, or stable disease (SD)
that lasts for at least 180 days.
[Time Frame: Baseline up to approximately 49 months]
7. Disease Control Rate (DCR) as Assessed by Blinded Independent Central Review and Investigator Review Based on RECIST v1.1
Disease control rate (DCR) is defined as the proportion of participants who have a confirmed BOR of CR, PR, or SD.
[Time Frame: Baseline up to approximately 49 months]
8. Time to Response (TTR) as Assessed by Blinded Independent Central Review and Investigator Review Based on RECIST v1.1
Time to response (TTR) is defined as the time from the date of randomization to the date of the first documentation of response (CR or PR) that is subsequently confirmed.
[Time Frame: Baseline up to approximately 49 months]
9. Mean Change from Baseline in Non-small Cell Lung Cancer - Symptom Assessment Questionnaire
The NSCLC-SAQ will assess disease-related symptom change in patients with NSCLC.
[Time Frame: Baseline up to approximately 49 months]
10. Mean Change from Baseline in Patient's Global Impression of Change
The PGI-C is a 7-point scale depicting a participant's rating of overall improvement.
[Time Frame: Baseline up to approximately 49 months]
11. Mean Change from Baseline in Patient's Global Impression of Severity
The PGI-S is a one-item questionnaire that contains six response options.
[Time Frame: Baseline up to approximately 49 months]
12. Mean Change from Baseline in Patient's Global Impression of Treatment Tolerability
The PGI-TT will capture the patient's overall impression of treatment tolerability.
[Time Frame: Baseline up to approximately 49 months]
13. Mean Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
The EORTC-QLQ-C30 will assess the patient's overall quality of life (QoL).
[Time Frame: Baseline up to approximately 49 months]
14. Mean Change from Baseline in EuroQol Questionnaire-5 dimensions-5 levels (EQ-5D-5L)
The EQ-5D-5L is a standardized instrument that will be used for measuring generic health status required for health technology assessments.
[Time Frame: Baseline up to approximately 49 months]
15. Number of Participants With Treatment-emergent Adverse Events
Treatment-emergent adverse events (TEAEs) will be graded by using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.
[Time Frame: Baseline up to approximately 49 months]
16. Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)
The immunogenicity of patritumab deruxtecan will be confirmed by assessing the anti-drug antibodies.
[Time Frame: Baseline up to approximately 49 months]
17. Percentage of Participants Who Have Treatment-emergent ADA
The immunogenicity of patritumab deruxtecan will be confirmed by assessing the anti-drug antibodies.
[Time Frame: Baseline up to approximately 49 months]
De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Information:
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/
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