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)
Study Details
Study Description
Brief Summary
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 BI 1810631 the participants can tolerate. Once this dose is found, it will be used in the second study part to tests whether BI 1810631 can make tumours shrink.
In this study, BI 1810631 is given to people for the first time. Participants take BI 1810631 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 BI 1810631.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase Ia - Dose escalation part Consecutive cohorts of patients treated with escalating doses of BI 1810631 monotherapy. |
Drug: BI 1810631
BI 1810631
|
| Experimental: Phase Ib - Dose expansion part
|
Drug: BI 1810631
BI 1810631
|
Outcome Measures
Primary Outcome Measures
- Phase Ia: Maximum Tolerated Dose (MTD) [At the end of Cycle 1 (each cycle is 21 days)]
Maximum tolerated dose is defined as the highest dose with less than 25% risk of the true Dose Limiting Toxicity (DLT) rate being equal to or above 33% during the MTD evaluation period in any studied regimen.
- Phase Ia: Number of patients with Dose Limiting Toxicities (DLTs) in the MTD evaluation period [At the end of Cycle 1 (each cycle is 21 days)]
- Phase Ib: Objective response (OR) [From the start of the trial treatment until end of month 12, up to 12 months]
OR is defined as best overall response of complete response (CR) or partial response (PR), where best overall response is determined according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 as assessed by the investigator, from the first treatment administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anticancer therapy, loss to follow-up or withdrawal of consent.
Secondary Outcome Measures
- Phase Ia: Number of patients experiencing DLTs during the entire treatment period [From the start of the trial treatment until end of month 8, up to 8 months]
- Phase Ia: Maximum measured concentration of BI 1810631 in plasma (Cmax) [On day 1 and on day 15 of Cycle 1 (each cycle is 21 days)]
- Phase Ia: Area under the concentration-time curve of BI 1810631 in plasma (AUC0-t2) [On day 1 and on day 15 of Cycle 1 (each cycle is 21 days)]
- Phase Ib: Duration of objective response (DoR) [From the start of the trial treatment until end of month 12, up to 12 months]
DoR is defined as the time from first documented complete response (CR) or partial response (PR) until the earliest of disease progression or death among patients with objective response.
- Phase Ib: Disease control (DC) [From the start of the trial treatment until end of month 12, up to 12 months]
DC is defined as best overall response of complete response (CR) or partial response (PR) or stable disease (SD) where best overall response is defined according to RECIST version 1.1 as assessed by the investigator, from until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow-up or withdrawal of consent.
- Phase Ib: Duration of disease control (DoDC) [From the start of the trial treatment until end of month 12, up to 12 months]
DoDC is defined as the time from first treatment administration until the earliest of disease progression or death, among patients with disease control.
- Phase Ib: Progression-free survival (PFS) [From the start of the trial treatment until end of month 12, up to 12 months]
PFS is defined as the time from first treatment administration until tumor progression according to RECIST version 1.1 as assessed by the investigator, or death from any cause, whichever occurs earlier.
- Phase Ib: Number of patients experiencing DLTs during the entire treatment period [From the start of the trial treatment until end of month 12, up to 12 months]
- Phase Ib: Maximum measured concentration of BI 1810631 in plasma (Cmax ) [On day 1 and on day 15 of Cycle 1 (each cycle is 21 days)]
- Phase Ib: Area under the concentration-time curve of BI 1810631 in plasma (AUC0-t2) [On day 1 and on day 15 of Cycle 1 (each cycle is 21 days)]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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 (RECIST) 1.1).
-
Eastern Cooperative Oncology Group score of 0 or 1
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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
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Patient willing to undergo a fresh tumour biopsy prior to first treatment and also 5-7 hours (h) after any treatment with BI 1810631 during cycle 1 (except biopsies of brain metastases) for pharmacodynamic assessments
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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
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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
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Creatinine ≤ 1.5 x ULN. If creatinine is > 1.5 x ULN, patient is eligible if concurrent creatinine clearance ≥ 50 ml/min (measured or calculated by Chronic Kidney Disease Epidemiology (CKD-EPI) formula or Japanese version of CKD-EPI formula for Japanese patients)
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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
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Alkaline Phosphatase < 5 x ULN
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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)
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Life expectancy of at least 12 weeks at the start of treatment in the opinion of the investigator
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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
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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
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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)
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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 Exon20 insertion-mutation positive non-small cell lung cancer (NSCLC) as per central lab results
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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 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
Exclusion Criteria:
-
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
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Previous or concomitant malignancies other than the one treated in this trial within the last 2 years, except;
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effectively treated non-melanoma skin cancers
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effectively treated carcinoma in situ of the cervix
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effectively treated ductal carcinoma in situ
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other effectively treated malignancy that is considered cured by local treatment.
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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
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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
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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)
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Treatment with strong Cytochrome P450 3A4 (CYP3A4) inhibitors
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Treatment with strong Cytochrome P450 3A (CYP3A) inducers Further exclusion criteria apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mary Crowley Cancer Research Center | Dallas | Texas | United States | 75230 |
| 2 | The University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 3 | Guangdong Provincial People's Hospital | Guangzhou | China | 510080 | |
| 4 | National Cancer Center Hospital East | Chiba, Kashiwa | Japan | 277-8577 | |
| 5 | National Cancer Center Hospital | Tokyo, Chuo-ku | Japan | 104-0045 | |
| 6 | Nederlands Kanker Instituut | Amsterdam | Netherlands | 1066 CX |
Sponsors and Collaborators
- Boehringer Ingelheim
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 1479-0001
- 2020-004563-47