Could targeting HER2 help us treat advanced cancer?
Despite considerable progress in cancer care, there remains a critical unmet need for strategies that improve outcomes for patients with advanced, unresectable solid tumors.1 One potentially transformative strategy could be the development of pan-tumor treatments that target specific biomarkers. HER2 is a particularly promising target because it drives oncogenesis in various tumor types and is associated with an aggressive tumor phenotype, poor prognosis, and limited benefits from chemotherapy.2–5
To date, HER2-directed treatments have improved outcomes for breast and gastric cancers, but there are limited options for other HER2-expressing solid tumors outside of these settings.6,7 Which is why we are conducting Beamion PANTUMOR-1 – a clinical study to see if an investigational drug called zongertinib could help patients with HER2-mutated or overexpressed/amplified solid tumors.
Key eligibility criteria
We are looking for approximately 200 adults to join Beamion PANTUMOR-1 who, among other criteria, have:
Locally advanced, unresectable, or metastatic solid tumors
A mutation or overexpression/amplification of HER2 (confirmed prior to screening)
Failed conventional treatments or have no other treatment options for their cancer
Patients are NOT eligible if they have:
Been diagnosed with HER2 overexpression/ amplified metastatic breast cancer or metastatic gastric, gastroesophageal junction, and esophageal adenocarcinoma
Been diagnosed with HER2 mutant non-small cell lung cancer
Been previously treated with a HER2 TKI in the advanced or metastatic setting
Have uncontrolled and/or symptomatic brain metastases or primary brain tumor
Known or suspected leptomeningeal disease
History or presence of uncontrolled gastrointestinal disorders that could affect the intake and/or absorption of zongertinib
Could any of your patients be eligible for this study?
If you think any of your patients could be eligible for this study, please consider screening their archival tumor biopsies for HER2, particularly in tumor types not yet commonly associated with HER2.
About zongertinib
- Beamion PANTUMOR-1 will investigate the safety and efficacy of zongertinib, a highly selective HER2 tyrosine kinase inhibitor (TKI) with a manageable safety profile.
- TKIs target and block the activity of tyrosine kinases, which play a key role in the cell signaling pathways that control the growth and spread of cancer cells.8
Study design
Beamion PANTUMOR-1 is a Phase II, open-label, clinical study to evaluate the efficacy and safety of zongertinib for the treatment of selected HER2-mutated or overexpressed/amplified solid tumors. It is a multi-cohort study, consisting of 10 cohorts: 8 are tumor-specific and 2 are tumor-agnostic. This study is split into three key periods:
Screening period
Eligibility for screening requires prior confirmation of a patient’s HER2 status by histological or cytological examination of an archival tumor biopsy. Once confirmed, patient eligibility will be assessed during a 28-day screening period by the study team.
Treatment period
Zongertinib will be dispensed to patients at a dose of 120 mg to be taken orally, once daily, until disease progression, unacceptable toxicity, death, withdrawal of consent, or discontinuation for any other reason.
Follow-up period
If zongertinib treatment is permanently discontinued, patients must attend an end-of-treatment visit and at least one follow-up visit.
Patients will be asked to visit the study clinic regularly (about once a week for approximately 2 months, and then every 3 weeks thereafter) for health assessments, which will include safety laboratory tests, physical examinations, and tumor assessments.
All patients will be given a study diary and asked to record their medication and food intake for 3 days prior to some of their clinic visits.
Study objectives and endpoints
- To assess the anti-tumor activity of zongertinib monotherapy in a variety of solid tumors.
- Evaluate efficacy, safety, tolerability, and the risk-benefit profile of zongertinib.
- Evaluate patient reported outcomes.
- Overall response (OR) – defined as the best overall response of confirmed complete response (CR) or confirmed partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, from the date of treatment start until the earliest date of disease progression (PD), death, last evaluable tumor assessment before the start of subsequent anti-cancer therapy, or study treatment discontinuation as assessed by central independent review.
- Duration of objective response (DOR) – defined as the time from first documented confirmed OR, according to RECIST 1.1, until the earliest date of PD or death among patients with confirmed OR, assessed by central independent review.
- Progression-free survival (PFS) – defined as the time from treatment start until the earliest date of tumor progression according to RECIST 1.1, assessed by central independent review, or death from any cause, whichever occurs first.
- Disease control (DC) – defined as best overall response (BOR) of CR, PR or stable disease (SD), where BOR is defined according to RECIST 1.1, from first treatment administration until the earliest of PD, death, last evaluable tumor assessment before the start of subsequent anti-cancer therapy, or treatment discontinuation, as assessed by central independent review.
- Occurrence of treatment-emergent adverse events.
- Change from baseline to Week 48, or PD if earlier, in the European Organisation for Research and Treatment of Cancer Item List 19 (EORTC IL 19; five-item physical functioning scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30]).
Next steps
If you know of any patients who may qualify, please consider confirming their HER2 status and referring them to this study. If you have any questions, or would like any further information, please do not hesitate to contact your nearest site. We will be happy to help. We would also be grateful if you could share this website with patients and colleagues in your oncology network.
References
- Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48.
- Oh DY, Bang YJ. HER2-targeted therapies - a role beyond breast cancer. Nat Rev Clin Oncol. 2020;17(1):33–48.
- Najjar MK, Manore SG, Regua AT, et al. Antibody-drug conjugates for the treatment of HER2-positive breast cancer. Genes (Basel). 2022;13(11):2065.
- Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82.
- Xing F, Gao H, Chen G, et al. CMTM6 overexpression confers trastuzumab resistance in HER2-positive breast cancer. Mol Cancer. 2023;22(1):6.
- Li Z, Chen S, Feng W, et al. A pan-cancer analysis of HER2 index revealed transcriptional pattern for precise selection of HER2-targeted therapy. EBioMedicine. 2020;62:103074.
- Meric-Bernstam F, Johnson AM, Dumbrava EEI, et al. Advances in HER2-targeted therapy: novel agents and opportunities beyond breast and gastric cancer. Clin Cancer Res. 2019;25(7):2033–41.
- Mongre RK, Mishra CB, Shukla AK, et al. Emerging importance of tyrosine kinase inhibitors against cancer: quo vadis to cure? Int J Mol Sci. 2021;22(21):11659.
- Heymach J, Opdam F, Barve M, et al. A Phase I, open-label, dose confirmation, escalation, and expansion trial of BI 1810631 as monotherapy in patients with advanced or metastatic solid tumors with HER2 aberrations. Clin Lung Cancer. 2023;24(2):e65–e68.