Beamion LUNG-1: An open label, Phase I dose escalation trial, with dose confirmation and expansion, of zongertinib (BI1810631) as monotherapy in patients with advanced or metastatic solid tumors with HER2 aberrations
A study to test different doses of BI 1810631 in people with different types of advanced cancer (solid tumours with changes in the HER2 gene).
Ogawa Shintaro
Boehringer Ingelheim
2-1-1, Osaki, Shinagawa-ku, Tokyo
+81-120-189-779
medchiken.jp@boehringer-ingelheim.com
Yamagami Tomohiro
Boehringer Ingelheim
2-1-1, Osaki, Shinagawa-ku, Tokyo
+81-120-189-779
medchiken.jp@boehringer-ingelheim.com
Not Recruiting
June. 22, 2021
July. 02, 2021
96
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
1.Histologically or cytologically confirmed diagnosis of an advanced, unresectable and or metastatic non haematologic malignancy. Patient must have measurable or evaluable lesions (according to Response Evaluation Criteria In Solid Tumors RECIST1.1).
2.Eastern Cooperative Oncology Group score of 0 to 2
3.Availability and patient willingness to provide a sample of tumour for confirmation of the patients Human epidermal growth factor receptor 2 (HER2) status. This sample can be archival material obtained at any time prior to study enrollment.
4.Patient willing to undergo a fresh tumour biopsy prior to first treatment and also 5 to 7 hours (h) after any treatment with BI 1810631 during cycle 1 (except biopsies of brain metastases) for pharmacodynamic assessments
5.Adequate organ function defined as all of the following: Absolute neutrophil count (ANC) greater than or equal to 1.5 times 109 perL (greater than or equal to1.5 times 103 per micro L) (greater than or equal to 1500 per mm3);haemoglobin greater than or equal to 9.0 g per dL (greater than or equal to 90 g per L) (greater than or equal to 5.6 mmol per L); platelets greater than or equal to 100 times 109 per L (100 times 103 per micro L) (100 times 103 per mm3) without the use of hematopoietic growth factors within 4 weeks of start of trial medication Total bilirubin less than or equal to 1.5 times the upper limit of normal (ULN), except for patients with Gilbert's syndrome: total bilirubin less than or equal to 3 times ULN or direct bilirubin less than or equal to 1.5 times ULN Creatinine less than or equal to 1.5 times ULN. If creatinine is more than 1.5 times ULN, patient is eligible if concurrent creatinine clearance greater than or equal to 50 ml per min (measured or calculated by Chronic Kidney Disease Epidemiology (CKD EPI) formula or Japanese version of CKD EPI formula for Japanese patients) Aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 3 times ULN if no demonstrable liver metastases, or otherwise less than or equal to 5 times ULN if transaminase elevation is attributable to liver metastases Alkaline Phosphatase less than 5 times ULN
6.Recovered from any previous therapy related toxicity to less than or equal 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 less than or equal to CTCAE Grade 2)
7.Life expectancy of at least 12 weeks at the start of treatment in the opinion of the investigator
8.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.
9.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.
10.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 percent 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;
Patient with documented HER2 tyrosine kinase domain mutation positive non small cell lung cancer (NSCLC) as per central lab results Patient who had received, in the advanced or metastatic setting, at least one line of systemic therapy. Patients with NSCLC harboring additionally genomic aberrations for which approved targeted therapy is available such as but not limited to non resistant epidermal growth factor receptor (EGFR) mutations, EGFR T790M mutation, Anaplastic lymphoma kinase (ALK) rearrangement, reactive oxygen species (ROS) re arrangement, and v raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutation, must have received prior treatment with an approved targeted therapy.
1.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
2.Previous or concomitant malignancies other than the one treated in this trial within the last 2 years, except; a)effectively treated non-melanoma skin cancers b)effectively treated carcinoma in situ of the cervix c)effectively treated ductal carcinoma in situ d)other effectively treated malignancy that is considered cured by local treatment.
3.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
4.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.
5.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)
6.Treatment with strong Cytochrome P450 3A4 (CYP3A4) inhibitors
7.Treatment with strong Cytochrome P450 3A (CYP3A) inducers
20age old over
No limit
Both
NSCLC
The Phase Ia dose escalation starting dose will be
BID Schedule: 15 mg twice daily
QD Schedule: 60 mg once daily (if not proposed otherwise by the DEC)
Dose-escalation steps will be determined by the Dose Escalation Committee (DEC)
The dose for the Phase Ib Dose Expansion part will be determined during the Dose Escalation part
Phase Ia part of the trial:
-MTD, based on number of dose-limiting toxicities (DLTs) during the MTD evaluation period.
-Number of patients with DLTs in the MTD evaluation period.
Phase Ib part of the trial:
-Objective response (OR), according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
Phase Ia part of the trial:
-Number of patients experiencing DLTs during the entire treatment period.
-PK parameters of BI 1810631: Cmax and AUC0-t2
Phase Ib part of the trial:
-Duration of objective response (DoR)
-Disease control (DC)
-Duration of disease control (DoDC)
-Progression-free survival (PFS)
-Number of patients experiencing DLTs during the entire treatment period
-PK parameters of BI 1810631: Cmax and AUC0-t2
