An Open Label, Phase I Dose Escalation Trial, With Dose Confirmation and Expansion, of BI 1810631 as Monotherapy in Patients With Advanced or Metastatic Solid Tumors With HER2 Aberrations
An Open Label, Phase I Dose Escalation Trial, With Dose Confirmation and Expansion, of BI 1810631 as Monotherapy in Patients With Advanced or Metastatic Solid Tumors With HER2 Aberrations
NCT #
NCT04886804
Condition(s)
Non-Small Cell Lung, Solid Tumor
Molecular Target(s)
HER2
Drug Classification(s)
Targeted Therapy
Agents(s)
BI 1810631
Phase(s)
I
Mechanism of Action
BI 1810631 is an EGFR wild type sparing, selective HER2 inhibitor with potent inhibitory activity on all oncogenic HER2 mutations including the HER2 YVMA insertion allele.
Purpose
- How much of the study drug can be given with an acceptable level of side effects
- About the safety, effectiveness and tolerability (side effects) of the study drug
- How much of the study drug is absorbed into the blood and how fast it is removed
- How proteins that indicate the status of your disease are affected with use of the study drug
- If research tests can be used in the future to predict who will benefit from BI 1810631
- If the study drug prevents or delays tumor growth
- Whether giving the study drug 1 or 2 times per day is more effective and which dose and regimen has less side effects in people with solid tumor type cancer
- 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 score of 0 or 1.
- 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 109/L (≥ 1.5 x 103/μL) (≥ 1500/mm3); haemoglobin ≥ 9.0 g/dL (≥ 90 g/L) (≥ 5.6 mmol/L); platelets ≥ 100 x 109/L (100 x 103/μL) (100 x 103/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.
- Male or female patients. Women of childbearing potential (WOCBP)1 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.
- 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
- Use of concomitant medications that are narrow therapeutic index drugs that are substrates of P-Glycoprotein (P-gp) or Breast Cancer Resistance
- Protein (BCRP) (e.g. digoxin, dabigatran etexilate)
- Treatment with strong Cytochrome P450 3A4 (CYP3A4) inhibitors
- Treatment with strong Cytochrome P450 3A (CYP3A) inducers Further exclusion criteria apply
Phase 1A: HER2 abberation Solid tumor, Phase Ib: HER2 Exon20 NSCLC, Pretreated NSCLC only: Previous treatment with any HER2 TKI
Location
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