SEVABERTINIB for Non-small cell lung cancer with HER2 (ERBB2) activating mutation

Inclusion criteria

• {"criterion_text":"- Participant must be ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signing the informed consent"}
• {"criterion_text":"- Documented histologically or cytologically confirmed locally advanced non-squamous NSCLC, not suitable for definitive therapy or metastatic non-squamous NSCLC at screening (small cell or mixed histologies are excluded) (Stage III-IV NSCLC)."}
• {"criterion_text":"- Documented activating HER2 mutation in the tyrosine kinase domain (TKD) assessed by tissue molecular test in a CLIA-certified (US sites) or an equally accredited (outside of the US) local laboratory. However, participants may be included at the discretion of the investigator if the laboratory performing the assay is not CLIA or similar certified but the laboratory is locally accredited."}
• {"criterion_text":"- No prior systemic therapy for locally advanced or metastatic disease.No prior treatment with a HER2 ex20ins-targeted therapy (e.g. poziotinib, trastuzumab deruxtecan). Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the start of screening"}
• {"criterion_text":"- Eligible to receive treatment with the selected platinum-based doublet-chemotherapy (i.e. cisplatin/pemetrexed or carboplatin/pemetrexed) and pembrolizumab in accordance with the SmPC/Product Information."}

Exclusion criteria

• {"criterion_text":"- Known history of prior malignancy other than the one treated in this study except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for five years since initiation of that therapy. Exception: the following cancer types are acceptable within five years if curatively treated or under surveillance: a. in situ cancers of cervix, breast, or skin, b. superficial bladder cancer (Ta, Tis and T1), c. limited-stage prostate cancer, d. basal or squamous cancers of the skin."}
• {"criterion_text":"- Tumors with targetable alterations with approved available therapy, with the exception of HER2 mutation in the TKD"}
• {"criterion_text":"- Inability to discontinue treatment with chronic systemic corticosteroids. Participants who require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. Replacement therapy (e.g., physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is acceptable, provided that the dose is stable for >4 weeks prior to planned start of study intervention."}
• {"criterion_text":"- Pre-existing peripheral neuropathy that is Grade ≥2 by CTCAE (v5.0)"}
• {"criterion_text":"- History of severe hypersensitivity reaction to treatment with a monoclonal antibody"}
• {"criterion_text":"- Prior radiotherapy outside of the brain within 21 days before the planned start of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids."}
• {"criterion_text":"- Participants with active brain metastases (i.e., new brain metastases or progressive brain metastases that have not been treated with CNS-directed therapy since documented progression) and/or leptomeningeal disease (i.e., positive cerebrospinal fluid cytology or unequivocal radiologic or clinical evidence of leptomeningeal involvement) are excluded. Participants with treated brain metastases who are asymptomatic at screening are eligible if all protocol criteria are met."}
• {"criterion_text":"- Lung-specific intercurrent clinically significant severe illness based on investigators assessment. Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management. Lymphangitic spread of the NSCLC is not exclusionary. Past medical history of Grade ≥2 ILD, any grade drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment within the last 12 months, or any Grade active pneumonitis/interstitial lung disease."}
• {"criterion_text":"- Refractory nausea and vomiting, chronic gastrointestinal disorders or diseases, clinically active diverticulitis, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis, malabsorption syndrome, inability to swallow the drug, or previous significant gastric/bowel resection that would preclude adequate absorption of sevabertinib."}

Primary endpoints

• {"endpoint_text":"- Progression free survival (PFS) per RECIST 1.1 as assessed by blinded independent central review (BICR)","definition_or_measurement_approach":"Per RECIST 1.1, assessed by Blinded Independent Central Review (BICR)"}

Secondary endpoints

• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":"Overall survival measured from randomisation to death (no further definition in record)"}
• {"endpoint_text":"- Objective response rate (ORR) per RECIST 1.1 as assessed by BICR","definition_or_measurement_approach":"ORR per RECIST 1.1, assessed by Blinded Independent Central Review (BICR)"}
• {"endpoint_text":"- PFS per RECIST 1.1 as assessed by the investigator","definition_or_measurement_approach":"Progression-free survival per RECIST 1.1 as assessed by investigator"}
• {"endpoint_text":"- ORR per RECIST 1.1 as assessed by the investigator","definition_or_measurement_approach":"Objective response rate per RECIST 1.1 assessed by investigator"}
• {"endpoint_text":"- Disease control rate (DCR) per RECIST 1.1 as assessed by BICR","definition_or_measurement_approach":"Disease control rate per RECIST 1.1, assessed by BICR"}
• {"endpoint_text":"- DCR per RECIST 1.1 as assessed by the investigator","definition_or_measurement_approach":"Disease control rate per RECIST 1.1 assessed by investigator"}
• {"endpoint_text":"- Duration of response (DOR) as assessed by BICR","definition_or_measurement_approach":"Duration of response per RECIST 1.1, assessed by BICR"}
• {"endpoint_text":"- DOR as assessed by the investigator","definition_or_measurement_approach":"Duration of response as assessed by investigator"}
• {"endpoint_text":"- Adverse events per CTCAE v 5.0 (eg. TEAEs, TESAEs) categorized by severity","definition_or_measurement_approach":"Adverse events graded and categorised using CTCAE v5.0 (treatment-emergent AEs, serious AEs etc.)"}
• {"endpoint_text":"- Change from baseline in Non-small cell lung cancer Symptom Assessment Questionnaire (NSCLC-SAQ) total score","definition_or_measurement_approach":"Patient-reported outcome measure: NSCLC-SAQ total score change from baseline"}
• {"endpoint_text":"- Change from baseline in NSCLC-SAQ individual domain scores (cough, pain, dyspnea, fatigue, appetite)","definition_or_measurement_approach":"NSCLC-SAQ domain scores for cough, pain, dyspnea, fatigue, appetite; change from baseline"}
• {"endpoint_text":"- Time to deterioration in NSCLC-SAQ total score","definition_or_measurement_approach":"Time-to-event analysis for deterioration in NSCLC-SAQ total score"}
• {"endpoint_text":"- Time to deterioration in NSCLC-SAQ individual domain scores (cough, pain, dyspnea, fatigue, appetite)","definition_or_measurement_approach":"Time-to-event analyses for deterioration in each NSCLC-SAQ domain"}
• {"endpoint_text":"- Time to deterioration in EORTC QLQ-C30 physical functioning domain score","definition_or_measurement_approach":"Time to deterioration on EORTC QLQ-C30 physical functioning domain"}
• {"endpoint_text":"- Change from baseline in EORTC QLQ-C30 physical functioning domain score","definition_or_measurement_approach":"Change from baseline on EORTC QLQ-C30 physical functioning domain"}
• {"endpoint_text":"- Change from baseine in EORTC QLQ-C30 global health status/QoL","definition_or_measurement_approach":"Change from baseline in EORTC QLQ-C30 global health status / quality of life"}

Methods

• Recruitment vendor: Massive Bio Inc. (listed as 'Recruitment Vendor' in sponsor third parties) — vendor contact recorded in sponsor thirdParties (skurnaz@massivebio.com).
• Online patient recruitment platform: Probando GmbH — listed duty 'Facilitate patient recruitment through online platform'.
• Digital/social media campaigns and site-specific recruitment materials: multiple K2_Recruitment_material and K1_Recruitment_arrangements documents listed (country-specific recruitment dossiers and social media campaign materials referenced for AT, DE, FI, PL, etc.).
• Site-based recruitment through participating hospitals/clinical sites (multiple hospital sites listed per country).

Slovakia

Earliest CTIS Part Ii Submission Date

12-09-2024

Latest Decision Or Authorization Date

04-10-2024

Processing Time Days

22

Number Of Participants

2

Poland

Earliest CTIS Part Ii Submission Date

13-09-2024

Latest Decision Or Authorization Date

07-10-2024

Processing Time Days

24

Number Of Participants

4

Austria

Earliest CTIS Part Ii Submission Date

16-09-2024

Latest Decision Or Authorization Date

07-10-2024

Processing Time Days

21

Number Of Participants

4

Finland

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

01-10-2024

Processing Time Days

28

Number Of Participants

2

Germany

Earliest CTIS Part Ii Submission Date

12-09-2024

Latest Decision Or Authorization Date

04-10-2024

Processing Time Days

22

Number Of Participants

14

Hungary

Earliest CTIS Part Ii Submission Date

04-09-2024

Latest Decision Or Authorization Date

04-10-2024

Processing Time Days

30

Number Of Participants

1

Sweden

Earliest CTIS Part Ii Submission Date

02-09-2024

Latest Decision Or Authorization Date

04-10-2024

Processing Time Days

32

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

01-10-2024

Processing Time Days

28

Number Of Participants

48

Spain

Earliest CTIS Part Ii Submission Date

11-09-2024

Latest Decision Or Authorization Date

01-10-2024

Processing Time Days

20

Number Of Participants

12

Belgium

Earliest CTIS Part Ii Submission Date

02-09-2024

Latest Decision Or Authorization Date

07-10-2024

Processing Time Days

35

Number Of Participants

3

Denmark

Earliest CTIS Part Ii Submission Date

17-09-2024

Latest Decision Or Authorization Date

30-09-2024

Processing Time Days

13

Number Of Participants

4

Bulgaria

Earliest CTIS Part Ii Submission Date

04-09-2024

Latest Decision Or Authorization Date

03-10-2024

Processing Time Days

29

Number Of Participants

7

Netherlands

Earliest CTIS Part Ii Submission Date

12-09-2024

Latest Decision Or Authorization Date

07-10-2024

Processing Time Days

25

Number Of Participants

6

Portugal

Earliest CTIS Part Ii Submission Date

04-09-2024

Latest Decision Or Authorization Date

02-10-2024

Processing Time Days

28

Number Of Participants

12

Czechia

Earliest CTIS Part Ii Submission Date

02-09-2024

Latest Decision Or Authorization Date

02-10-2024

Processing Time Days

30

Number Of Participants

4

Greece

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

01-10-2024

Processing Time Days

28

Number Of Participants

7

France

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

30-09-2024

Processing Time Days

25

Number Of Participants

32

Romania

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

07-10-2024

Processing Time Days

34

Number Of Participants

10

Primary sponsor

Full Name

Bayer AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

4g Clinical LLC

Name

Cytel Inc.

Name

Eresearchtechnology Inc.

Third parties

• {"country":"United States","full_name":"Massive Bio Inc.","duties_or_roles":"Recruitment Vendor","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Nuvisan GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Burning Rock Dx LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Predicine Inc.","duties_or_roles":"Analysis of biomarker plasma samples","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Laboratory Corporation Of America Holdings","duties_or_roles":"Analysis of histology samples","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Austria","full_name":"Probando GmbH","duties_or_roles":"Facilitate patient recruitment through online platform","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Diagnostic Services Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"China","full_name":"Q Squared Solutions (Beijing) Co. Ltd.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Life Technologies Clinical Services Lab Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Canada","full_name":"Altis Labs Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"Biosample storage","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"China","full_name":"Guangzhou Burning Rock Dx Co. Ltd.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Diagnostic Services LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}