A study to learn more about how well sevabertinib works and how safe it is compared with standard treatment, in participants who have advanced non-small cell lung cancer (NSCLC) with mutations of the human epidermal growth factor receptor 2 (HER2)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bayer AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Oct 2024 → ongoing

Decision date (initial)

2024-10-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bayer AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic, Pharmacogenetic, Efficacy

To evaluate the effect of sevabertinib compared with SoC in progression free survival (PFS)

Secondary objectives 6

1. To evaluate the efficacy of sevabertinib compared with SoC in overall survival (OS)
2. To evaluate the efficacy of sevabertinib compared with SoC in objective response rate (ORR)
3. To evaluate the effect of sevabertinib compared with SoC in PFS
4. To further characterize the efficacy of sevabertinib compared with SoC
5. To assess the safety and tolerability of sevabertinib compared with SoC
6. To evaluate patient-reported outcomes (PROs) of sevabertinib compared with SoC

Conditions and MedDRA coding

Advanced non-small cell lung cancer with HER2 (ERBB2) mutation

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

IPD plan description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 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
2. 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).
3. 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.
4. 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
5. 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 9

1. 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.
2. Tumors with targetable alterations with approved available therapy, with the exception of HER2 mutation in the TKD
3. 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.
4. Pre-existing peripheral neuropathy that is Grade ≥2 by CTCAE (v5.0)
5. History of severe hypersensitivity reaction to treatment with a monoclonal antibody
6. 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.
7. Οι συμμετέχοντες με ενεργές εγκεφαλικές μεταστάσεις (δηλαδή, νέες εγκεφαλικές μεταστάσεις ή εγκεφαλικές μεταστάσεις με πρόοδο νόσου που δεν έχουν υποβληθεί σε στοχευμένη θεραπεία ΚΝΣ μετά την τεκμηριωμένη πρόοδο νόσου) και/ή λεπτομηνιγγική νόσο (δηλ. θετική κυτταρολογία εγκεφαλονωτιαίου υγρού ή αναμφισβήτητες ακτινολογικές ή κλινικές ενδείξεις λεπτομηνιγγικής συμμετοχής) εξαιρούνται. Οι συμμετέχοντες με εγκεφαλικές μεταστάσεις που έχουν υποβληθεί σε θεραπεία και είναι ασυμπτωματικές κατά τον προκαταρκτικό έλεγχο είναι επιλέξιμοι εάν πληρούνται όλα τα κριτήρια του πρωτοκόλλου.
8. 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.
9. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression free survival (PFS) per RECIST 1.1 as assessed by blinded independent central review (BICR)

Secondary endpoints 16

1. Overall survival (OS)
2. Objective response rate (ORR) per RECIST 1.1 as assessed by BICR
3. PFS per RECIST 1.1 as assessed by the investigator
4. ORR per RECIST 1.1 as assessed by the investigator
5. Disease control rate (DCR) per RECIST 1.1 as assessed by BICR
6. DCR per RECIST 1.1 as assessed by the investigator
7. Duration of response (DOR) as assessed by BICR
8. DOR as assessed by the investigator
9. Adverse events per CTCAE v 5.0 (eg. TEAEs, TESAEs) categorized by severity
10. Change from baseline in Non-small cell lung cancer Symptom Assessment Questionnaire (NSCLC-SAQ) total score
11. Change from baseline in NSCLC-SAQ individual domain scores (cough, pain, dyspnea, fatigue, appetite)
12. Time to deterioration in NSCLC-SAQ total score
13. Time to deterioration in NSCLC-SAQ individual domain scores (cough, pain, dyspnea, fatigue, appetite)
14. Time to deterioration in EORTC QLQ-C30 physical functioning domain score
15. Change from baseline in EORTC QLQ-C30 physical functioning domain score
16. Change from baseine in EORTC QLQ-C30 global health status/QoL

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bayer AG

Sponsor organisation

Bayer AG

Address

-

City

Leverkusen

Postcode

51368

Country

Germany

Scientific contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Public contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Third parties 17

Locations

18 EU/EEA countries · 112 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 190 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications