Beamion PANTUMOR-1: A study to test whether zongertinib helps people with advanced cancers with HER2 alterations

JRCT ID: jRCT2031240349

Registered date:25/09/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Solid Tumours
• Date of first enrollment: 31/10/2024
• Target sample size: 18
• Countries of recruitment: Australia,Japan,Belgium,Japan,Canada,Japan,China,Japan,France,Japan,Germany,Japan,Italy,Japan,Netherlands,Japan,Norway,Japan,South Korea,Japan,Spain,Japan,USA,Japan
• Study type: Interventional
• Intervention(s): Oral dose of zongertinib each day until criteria for stopping medication are met.

Outcome(s)

Primary Outcome

Objective response (OR) is defined as the best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1, as assessed by central independent review, from the date of treatment start until the earliest date of progressive disease (PD), death, or last evaluable tumour assessment
before the start of subsequent anti-cancer therapy, or trial treatment discontinuation.

Secondary Outcome

- Duration of objective response (DOR) is defined as the time from first documented confirmed OR according to RECIST 1.1 until the earliest date of disease progression or death among patients with confirmed objective response, assessed by central independent review.
- Progression-free survival (PFS) is defined as the time from treatment start until the earliest date of tumour progression according to RECIST 1.1 assessed by central independent review, or death from any cause, whichever occurs first.
- Disease control (DC) is defined as best overall response of CR or PR or stable disease (SD) where best overall response is defined according to RECIST 1.1 from first treatment administration until the earliest of disease progression, death, or last evaluable tumour assessment before the start of subsequent anti-cancer therapy, or treatment discontinuation, as assessed by central independent review.
- Occurrence of treatment-emergent AEs.
- Change from baseline to Week 48 or PD, if earlier, in the European Organisation for Research and Treatment of Cancer item list (EORTC IL19) (5 items, physical functioning scale of EORTC quality of life questionnaire (QLQ-C30).

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Main inclusion criteria
1. Patients >=18 years old or over the legal age of consent in countries where that is greater than 18 years at the time of signature of theICF.
2. Documented (previously established by local testing) HER2 status of:
a. Cohorts 1 to 6: HER2 overexpression amplification (with or without HER2 mutations) defined as:
i. HER2 IHC 3+ by gastric algorithm according to ASCO/CAP gastric cancer guidelines, or
ii. HER2 IHC 2+ and HER2 amplification by ISH according to ASCO/CAP gastric cancer guidelines, or
iii. HER2 amplification in archival (enrolment) tissue by next generation sequencing (NGS) assay, or
iv. HER2 amplification in ctDNA by blood based NGS assay and investigator confirmation by IHC ISH according to ASCO CAP gastric cancer guidelines prior to or in parallel with the screening process
b. Cohorts 7 to 10: Known activating HER2 mutations (without overexpression/ amplification) detected in archival (enrolment) tumour tissue or blood by NGS (acceptable mutations are listed in the ISF). Polymerase chain reaction (PCR) is also acceptable, but NGS is preferred.
3. An archival (enrolment) tumour tissue sample must be submitted after inclusion of the patient to retrospectively confirm the HER2 status (enrolment tissue sample). If no archival tissue is available, this may be acceptable in exceptional cases after written agreement with the sponsor. Please note that sample must not be from an area irradiated prior to the biopsy.
4. A tissue sample, either archival sample taken <=6 months prior to enrolment or a fresh biopsy, must be submitted after inclusion of the patient for biomarker analysis (biomarker tumour tissue). If it is not possible to provide tissue, this may be acceptable in exceptional cases after written agreement with the sponsor. Please note that sample must not be from an area irradiated prior to the biopsy and biopsies from brain metastases are not allowed.
5. Patient who has failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options. Patient must have exhausted, or not be a suitable candidate for, available treatment options known to prolong survival for their disease.
6. Recovered from any previous therapy-related toxicity to <= CTCAE Grade 1 at start of treatment (except for alopecia, stable sensory neuropathy, and hypothyroidism [patients on thyroid replacement therapy] which all must be <= CTCAE Grade 2).
7. Presence of at least 1 measurable lesion outside the CNS according to RECIST 1.1, as determined by the local site investigator/radiology assessment.
8. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1

Exclude criteria

Main Exclusion criteria
1. Diagnosis of HER2 overexpressing/amplified (IHC3+ or IHC2+/ISH+) mBC or mGEAC
2. Diagnosis of HER2 mutant NSCLC
3. Previous treatment with any HER2 tyrosine kinase inhibitors (TKIs) including, but not limited to, lapatinib, afatinib, neratinib, or dacomitinib in the advanced or metastatic setting. In the case of use in the adjuvant setting, at least 12 months must have passed prior to the start of trial drug
Note: prior antibody-drug conjugates (ADCs) are allowed.
4. Previous or concomitant malignancies other than the 1 treated in this trial within the previous 3 years except:
5. effectively treated non-melanoma skin cancers
6. effectively treated carcinoma in situ of the cervix
7. effectively treated ductal carcinoma in situ
8. other effectively treated malignancy that is considered cured by local treatment
9. Uncontrolled and/or symptomatic brain metastases or primary brain tumour. Subjects with known CNS lesions will be excluded if any of the following applies:
a. Any untreated brain lesions >2.0 cm in size, unless discussed with the medical monitor and approved for enrolment
b. Ongoing use of systemic corticosteroids for control of symptoms of brain lesions at a total daily dose of >2 mg of dexamethasone (or equivalent). However, subjects on a chronic stable dose of <=2 mg total daily of dexamethasone (or equivalent) may be eligible, following approval of medical monitor
c. Any brain lesion thought to require immediate local therapy, including (but not limited to) a lesion in an anatomic site where increase in size or possible treatment-related edema may pose risk to subject (e.g. brain stem lesions). Subjects who undergo local treatment for such lesions identified by screening brain MRI may still be eligible for the trial if all of the following criteria are met:
i. Time since whole brain radiotherapy is >=21 days prior to first dose of treatment, time since stereotactic radiosurgery is >=7 days prior to first dose of treatment, or time since surgical resection is >=28 days
ii. Other sites of disease assessable by RECIST 1.1 are present
d. Known or suspected leptomeningeal disease as documented by the investigator
e. Have poorly controlled (>1 per week) generalised or complex partial seizures, or manifest neurologic progression due to brain lesions notwithstanding CNS-directed therapy
10. Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial
11. Palliative radiotherapy within 2 weeks prior to start of treatment.
12. Not completely recovered from major surgery (major according to the investigators assessment) performed prior to screening or planned within 6 months after screening, e.g. hip replacement
13. Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patients ability to comply with the trial or interfere with the evaluation of the safety and efficacy of the test drug
14. History or presence of cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of >= III or IV, unstable angina or poorly controlled arrhythmia, which are considered as clinically relevant by the investigator. Myocardial infarction (or troponin levels consistent with myocardial infarction within 28 days of the start of treatment), stroke, or pulmonary embolism within 6 months prior to the start of treatment
15. Any clinically important abnormalities (as assessed by the investigator) in rhythm, conduction, or morphology of resting ECGs, e.g. complete left bundle branch block, third degree heart block
16. Mean resting corrected QT interval (QTcF) >470 msec (females) or >450 msec (males) based on screening 12-lead ECG
17. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication known to prolong the QT interval
18. Ejection fraction <50% or the lower limit of normal of the institutional standard within 28 days prior to the start of treatment

Related Information

• Primary Sponsor: Hagimori Kenta
• Secondary ID(s): NCT06581432