Informations générales (source: ClinicalTrials.gov)
Beamion LUNG-1: An Open Label, Phase I Dose Escalation Trial, With Dose Confirmation and Expansion, of Zongertinib (BI 1810631) as Monotherapy in Patients With Advanced or Metastatic Solid Tumors With HER2 Aberrations
Interventional
Phase 1
Boehringer Ingelheim (Voir sur ClinicalTrials)
juillet 2021
août 2028
29 juillet 2025
The study has 2 parts. The first part is open to adults with different types of advanced
cancer (solid tumours with changes in the HER2 gene) for whom previous treatment was not
successful.
The second part is open to people with non-small cell lung cancer with a specific
mutation in the HER2 gene.
The purpose of the first study part is to find the highest dose of a medicine called
zongertinib the participants can tolerate. Once this dose is found, it will be used in
the second study part to test whether zongertinib can make tumours shrink.
In this study, zongertinib is given to people for the first time. Participants take
zongertinib as tablets once a day or twice a day.
The participants are in the study for as long as they benefit from and can tolerate
treatment.
Study doctors regularly check the participants' health and monitor the tumours. The
doctors also take note of any unwanted effects that could have been caused by
zongertinib.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 10/04/2025 13:12:10 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | David PLANCHARD | 29/05/2024 15:44:23 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CTR Leon Berard - 69373 - Lyon - France | Contact (sur clinicalTrials) | ||||
| HOP Louis Pradel - 69677 - Bron - France | Contact (sur clinicalTrials) | ||||
| HOP Pontchaillou - 35000 - Rennes - France | Contact (sur clinicalTrials) | ||||
| HOP Timone - 13385 - Marseille - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of an advanced, unresectable
and/or metastatic non-haematologic malignancy. Patient must show presence of at
least one measurable lesion according to Response Evaluation Criteria In Solid
Tumors (RECIST) 1.1.
- Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 (ECOG=2 only for
Cohorts 6 and 7) .
- Availability and patient willingness to provide a sample of tumour for confirmation
of the patient´s Human epidermal growth factor receptor 2 (HER2) status. This sample
can be archival material obtained at any time prior to study enrollment.
- Patient willing and able to comply with the protocol requirements for tumour
biopsies (biopsies from brain metastases are not allowed).
- Adequate organ function defined as all of the following:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (≥ 1.5 x 10^3/μL) (≥ 1500/mm^3);
haemoglobin ≥ 9.0 g/dL (≥ 90 g/L) (≥ 5.6 mmol/L); platelets ≥ 100 x 10^9/L (100
x 10^3/μL) (100 x 10^3/mm3) without the use of hematopoietic growth factors
within 4 weeks of start of trial medication.
- Total bilirubin ≤ 1.5 times the upper limit of normal (ULN), except for
patients with Gilbert's syndrome: total bilirubin ≤ 3 x ULN or direct bilirubin
≤ 1.5 x ULN.
- Estimated Glomerular Filtration Rate (eGFR) ≥ 50 mL/min - calculated using
Chronic Kidney Disease Epidemiology (CKD-EPI) formula.
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN if no
demonstrable liver metastases, or otherwise ≤ 5 x ULN if transaminase elevation
is attributable to liver metastases.
- Alkaline Phosphatase < 5 x ULN.
- Recovered from any previous therapy-related toxicity to ≤ Common Terminology
Criteria for Adverse Events (CTCAE) Grade 1 at start of treatment (except for
alopecia, stable sensory neuropathy and hypothyroidism (patients on thyroid
replacement therapy) which must be ≤ CTCAE Grade 2)
- Life expectancy of at least 12 weeks at the start of treatment in the opinion of the
investigator.
- At least 18 years of age at the time of consent or over the legal age of consent in
countries where that is greater than 18 years.
- Signed and dated written informed consent in accordance with International Council
on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to
admission to the trial.
- Male or female patients. Women of childbearing potential (WOCBP) and men who are
able to father a child must be ready and able to use highly effective methods of
birth control per International Council on Harmonisation (ICH) M3 (R2) that result
in a low failure rate of less than 1% per year when used consistently and correctly.
Additional inclusion criteria for Phase Ia
- Patients with a documented diagnosis of HER2 aberration: overexpression OR gene
amplification OR non-synonymous somatic mutation OR gene rearrangement involving
HER2 or Neuregulin 1 (NRG1)
- 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
Additional inclusion criteria for Phase Ib - Cohort 1 only
- Non-squamous non-small cell lung cancer (NSCLC) patients with documented human
epidermal growth factor receptor 2 (HER2) mutation in the tyrosine kinase domain
(TKD) as per local lab results.
- Patient who had received, in the advanced/metastatic setting, at least one line of
systemic therapy. Patients with non-squamous NSCLC harboring additionally genomic
aberrations for which approved targeted therapy is available as standard of care.
Additional inclusion criteria for Phase Ib - Cohort 2 only
- Non-squamous NSCLC patient with a documented HER2 mutation in the tyrosine kinase
domain (TKD) as per local lab results.
- Treatment naïve for non-squamous NSCLC.
Additional inclusion criteria for Phase Ib - Cohort 3 only
- NSCLC Patient with a documented HER2 mutation outside of the tyrosine kinase domain
(TKD) as per local lab results or squamous NSCLC patient with mutation in the TKD as
per local lab results.
- Patient who had received, in the advanced/metastatic setting, at least one line of
systemic therapy. Patients with NSCLC harboring additionally genomic aberrations for
which approved targeted therapy is available as standard of care.
Additional inclusion criteria for Phase Ib - Cohort 4 only
- NSCLC patients with documented HER2 mutation in the TKD as per local lab results.
- NSCLC patients who are either treatment naïve or who had received any prior line of
treatment, in the advanced/metastatic setting. Patients with NSCLC harboring
additional genomic aberrations for which approved targeted therapy is available as
standard of care.
- Patient with active brain metastases who are not eligible for immediate local
therapy, as per investigator evaluation.
Additional inclusion criteria for Phase Ib - Cohort 5 only
- Non-squamous NSCLC patients with documented HER2 mutation in the TKD as per local
lab results.
- Patient should have received, in the advanced/metastatic setting, at least one line
of systemic therapy that includes a platinum-based combination chemotherapy and
should have been treated with previous HER2 directed antibody-drug conjugates (ADC)
in the same advanced/metastatic setting and developed disease progression recurrence
during or after completing this therapy. Patients with NSCLC harboring additional
genomic aberrations for which approved targeted therapy is available as standard of
care.
Additional inclusion criteria for Phase Ib - Cohort 6 only
- Non-squamous NSCLC Patient with documented HER2 mutation in the TKD as per local lab
results.
- Patient who had received, in the advanced/metastatic setting, at least one line of
systemic therapy.
- Patient without active brain metastases or patient with active brain metastases who
are not eligible for immediate local therapy, as per investigator evaluation.
- Patient who is not eligible for any other recruiting cohort.
Additional inclusion criteria for Phase Ib - Cohort 7 only
- Non-squamous NSCLC patient with documented HER2 mutation in the TKD as per local lab
results.
- Patient who had received, in the advanced/metastatic setting, at least one line of
systemic therapy.
- Patient without active brain metastases or patient with active brain metastases who
are not eligible for immediate local therapy, as per investigator evaluation.
- Patient who is not eligible for any other recruiting cohort.
Additional inclusion criteria for Phase Ib - Cohort 8 only
- Treatment naïve for NSCLC
- NSCLC (adenocarcinoma or squamous) patient with documented HER2 mutation in the
tyrosine kinase domain (TKD) or non-squamous NSCLC with a documented HER2 mutation
in the non tyrosine kinase domain (non TKD) as per local lab results
Further inclusion criteria apply.
- Histologically or cytologically confirmed diagnosis of an advanced, unresectable
and/or metastatic non-haematologic malignancy. Patient must show presence of at
least one measurable lesion according to Response Evaluation Criteria In Solid
Tumors (RECIST) 1.1.
- Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 (ECOG=2 only for
Cohorts 6 and 7) .
- Availability and patient willingness to provide a sample of tumour for confirmation
of the patient´s Human epidermal growth factor receptor 2 (HER2) status. This sample
can be archival material obtained at any time prior to study enrollment.
- Patient willing and able to comply with the protocol requirements for tumour
biopsies (biopsies from brain metastases are not allowed).
- Adequate organ function defined as all of the following:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (≥ 1.5 x 10^3/μL) (≥ 1500/mm^3);
haemoglobin ≥ 9.0 g/dL (≥ 90 g/L) (≥ 5.6 mmol/L); platelets ≥ 100 x 10^9/L (100
x 10^3/μL) (100 x 10^3/mm3) without the use of hematopoietic growth factors
within 4 weeks of start of trial medication.
- Total bilirubin ≤ 1.5 times the upper limit of normal (ULN), except for
patients with Gilbert's syndrome: total bilirubin ≤ 3 x ULN or direct bilirubin
≤ 1.5 x ULN.
- Estimated Glomerular Filtration Rate (eGFR) ≥ 50 mL/min - calculated using
Chronic Kidney Disease Epidemiology (CKD-EPI) formula.
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN if no
demonstrable liver metastases, or otherwise ≤ 5 x ULN if transaminase elevation
is attributable to liver metastases.
- Alkaline Phosphatase < 5 x ULN.
- Recovered from any previous therapy-related toxicity to ≤ Common Terminology
Criteria for Adverse Events (CTCAE) Grade 1 at start of treatment (except for
alopecia, stable sensory neuropathy and hypothyroidism (patients on thyroid
replacement therapy) which must be ≤ CTCAE Grade 2)
- Life expectancy of at least 12 weeks at the start of treatment in the opinion of the
investigator.
- At least 18 years of age at the time of consent or over the legal age of consent in
countries where that is greater than 18 years.
- Signed and dated written informed consent in accordance with International Council
on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to
admission to the trial.
- Male or female patients. Women of childbearing potential (WOCBP) and men who are
able to father a child must be ready and able to use highly effective methods of
birth control per International Council on Harmonisation (ICH) M3 (R2) that result
in a low failure rate of less than 1% per year when used consistently and correctly.
Additional inclusion criteria for Phase Ia
- Patients with a documented diagnosis of HER2 aberration: overexpression OR gene
amplification OR non-synonymous somatic mutation OR gene rearrangement involving
HER2 or Neuregulin 1 (NRG1)
- 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
Additional inclusion criteria for Phase Ib - Cohort 1 only
- Non-squamous non-small cell lung cancer (NSCLC) patients with documented human
epidermal growth factor receptor 2 (HER2) mutation in the tyrosine kinase domain
(TKD) as per local lab results.
- Patient who had received, in the advanced/metastatic setting, at least one line of
systemic therapy. Patients with non-squamous NSCLC harboring additionally genomic
aberrations for which approved targeted therapy is available as standard of care.
Additional inclusion criteria for Phase Ib - Cohort 2 only
- Non-squamous NSCLC patient with a documented HER2 mutation in the tyrosine kinase
domain (TKD) as per local lab results.
- Treatment naïve for non-squamous NSCLC.
Additional inclusion criteria for Phase Ib - Cohort 3 only
- NSCLC Patient with a documented HER2 mutation outside of the tyrosine kinase domain
(TKD) as per local lab results or squamous NSCLC patient with mutation in the TKD as
per local lab results.
- Patient who had received, in the advanced/metastatic setting, at least one line of
systemic therapy. Patients with NSCLC harboring additionally genomic aberrations for
which approved targeted therapy is available as standard of care.
Additional inclusion criteria for Phase Ib - Cohort 4 only
- NSCLC patients with documented HER2 mutation in the TKD as per local lab results.
- NSCLC patients who are either treatment naïve or who had received any prior line of
treatment, in the advanced/metastatic setting. Patients with NSCLC harboring
additional genomic aberrations for which approved targeted therapy is available as
standard of care.
- Patient with active brain metastases who are not eligible for immediate local
therapy, as per investigator evaluation.
Additional inclusion criteria for Phase Ib - Cohort 5 only
- Non-squamous NSCLC patients with documented HER2 mutation in the TKD as per local
lab results.
- Patient should have received, in the advanced/metastatic setting, at least one line
of systemic therapy that includes a platinum-based combination chemotherapy and
should have been treated with previous HER2 directed antibody-drug conjugates (ADC)
in the same advanced/metastatic setting and developed disease progression recurrence
during or after completing this therapy. Patients with NSCLC harboring additional
genomic aberrations for which approved targeted therapy is available as standard of
care.
Additional inclusion criteria for Phase Ib - Cohort 6 only
- Non-squamous NSCLC Patient with documented HER2 mutation in the TKD as per local lab
results.
- Patient who had received, in the advanced/metastatic setting, at least one line of
systemic therapy.
- Patient without active brain metastases or patient with active brain metastases who
are not eligible for immediate local therapy, as per investigator evaluation.
- Patient who is not eligible for any other recruiting cohort.
Additional inclusion criteria for Phase Ib - Cohort 7 only
- Non-squamous NSCLC patient with documented HER2 mutation in the TKD as per local lab
results.
- Patient who had received, in the advanced/metastatic setting, at least one line of
systemic therapy.
- Patient without active brain metastases or patient with active brain metastases who
are not eligible for immediate local therapy, as per investigator evaluation.
- Patient who is not eligible for any other recruiting cohort.
Additional inclusion criteria for Phase Ib - Cohort 8 only
- Treatment naïve for NSCLC
- NSCLC (adenocarcinoma or squamous) patient with documented HER2 mutation in the
tyrosine kinase domain (TKD) or non-squamous NSCLC with a documented HER2 mutation
in the non tyrosine kinase domain (non TKD) as per local lab results
Further inclusion criteria apply.
- Major surgery (major according to the investigator's assessment) performed within 4
weeks prior to first trial treatment or planned within 6 months after screening
- Previous or concomitant malignancies other than the one treated in this trial within
the last 2 years, except:
- effectively treated non-melanoma skin cancers
- effectively treated carcinoma in situ of the cervix
- effectively treated ductal carcinoma in situ
- other effectively treated malignancy that is considered cured by local
treatment.
- Treatment with a systemic anti-cancer therapy or investigational drug within 21 days
or 5 half-lives (whichever is shorter) of the first treatment with the study
medication
- Patients who must or wish to continue the intake of restricted medication or any
drug considered likely to interfere with the safe conduct of the trial
- Previous treatment with zongertinib.
- Radiotherapy within 2 weeks prior to first study treatment, except palliative
radiotherapy to regions other than the chest, which is allowed up to 1 week prior to
first study treatment.
Further exclusion criteria apply