Phase III study of Patritumab-Deruxtecan compared to platinum-based chemotherapy in metastatic or locally advanced EGFRm-NSCLC after failure of EGFR-TKI therapy EGFRm: Mutation of the epidermal growth factor receptor NSCLC: non-small cell lung cancer TKI: Tyrosine kinase inhibitor

Australia, Austria, Belgium, Canada, China, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Netherlands, Norway, Poland, Portugal, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States (ICTRP)

ICTRP Trial ID
NCT05338970 (ICTRP)

Official title (approved by ethics committee)
HERTHENA–Lung02: 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 (BASEC)

Academic title
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) (ICTRP)

Public title
HERTHENA-Lung02: A Study of Patritumab Deruxtecan Versus Platinum-based Chemotherapy in Metastatic or Locally Advanced EGFRm NSCLC After Failure of EGFR TKI Therapy (ICTRP)

Disease under investigation
Nonsquamous Non-small Cell Lung Cancer;EGFR L858R;EGFR Exon 19 Deletion (ICTRP)

Intervention under investigation
Drug: Patritumab Deruxtecan;Drug: Platinum-based chemotherapy (ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Inclusion/Exclusion criteria
Gender: All
Maximum age: N/A
Minimum age: 18 Years
Inclusion Criteria:

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 ? 10^9/L within 14 days prior to the
assessment of platelet count during the Screening Period

- Absolute neutrophil count: =1500/mm^3 or =1.5 ? 10^9/L within 14 days prior to
the assessment of absolute neutrophil count during the Screening Period

- Hemoglobin (Hgb): =9.0 g/dL within 14 days prior to the assessment of
hemoglobin during the Screening Period

- 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?
Upper limit of normal (ULN)

- Total bilirubin (TBL): TBL =1.5 ? 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 ? 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

Exclusion Criteria:

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 any history of or evidence of current 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 (ICTRP)

not available

Primary and secondary end points
Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) Based on RECIST v1.1 (ICTRP)

Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline);Overall Survival (OS);Progression-free Survival (PFS) as Assessed by Investigator Review Based on RECIST v1.1;Progression-free Survival (PFS) as Assessed by Local Standard Clinical Practice;Objective Response Rate (ORR) as Assessed by BICR and Investigator Review Based on RECIST v1.1;Duration of Response (DoR) as Assessed by BICR and Investigator Review Based on RECIST v1.1;Clinical Benefit Rate (CBR) as Assessed by BICR and Investigator Review Based on RECIST v1.1;Disease Control Rate (DCR) as Assessed by BICR and Investigator Review Based on RECIST v1.1;Time to Response (TTR) as Assessed by BICR and Investigator Review Based on RECIST v1.1;Intracranial PFS as Assessed by BICR;Mean Change from Baseline in Non-small Cell Lung Cancer - Symptom Assessment Questionnaire;Mean Change from Baseline in Patient's Global Impression of Change;Mean Change from Baseline in Patient's Global Impression of Severity;Mean Change from Baseline in Patient's Global Impression of Treatment Tolerability;Mean Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30);Mean Change from Baseline in EuroQol Questionnaire-5 dimensions-5 levels (EQ-5D-5L);Number of Participants With Treatment-emergent Adverse Events (TEAEs);Percentage of Participants Who Have Treatment-emergent ADA (ICTRP)

Registration date
not available

Incorporation of the first participant
not available

Secondary sponsors
Merck Sharp & Dohme LLC (ICTRP)

Additional contacts
Global Clinical Leader;Clinical Scientist, Daiichi Sankyo,Daiichi Sankyo (ICTRP)

Secondary trial IDs
2021-005879-40, jRCT 2021220002, U31402-A-U301 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT05338970 (ICTRP)