BI 894999 First in Human Dose Finding Study in Advanced M... | NCT02516553

NCT02516553

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2015-001111-12	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

No data available

No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase Ia - Schedule A: 0.2 mg BI 894999	Experimental	Once daily continuous oral intake in 3-week cycles.	Drug: BI 894999
Phase Ia - Schedule A: 0.5 mg BI 894999	Experimental	Once daily continuous oral intake in 3-week cycles.	Drug: BI 894999
Phase Ia - Schedule A: 1 mg BI 894999	Experimental	Once daily continuous oral intake in 3-week cycles.	Drug: BI 894999
Phase Ia - Schedule A: 1.5 mg BI 894999	Experimental	Once daily continuous oral intake in 3-week cycles.	Drug: BI 894999
Phase Ia - Schedule A: 2 mg BI 894999	Experimental	Once daily continuous oral intake in 3-week cycles.	Drug: BI 894999
Phase Ia - Schedule A: 5 mg BI 894999	Experimental	Once daily continuous oral intake in 3-week cycles.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
BI 894999	Drug	film-coated tablets	Phase Ia - Schedule A: 0.2 mg BI 894999 Phase Ia - Schedule A: 0.5 mg BI 894999 Phase Ia - Schedule A: 1 mg BI 894999

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Phase Ia: Number of Patients With DLTs Observed in the First Cycle	Number of patients with Dose Limiting Toxicities (DLTs) observed in the first treatment cycle of Phase Ia is reported. The following drug related adverse events (AEs) qualified as DLT: any Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 non haematological toxicity considered related to trial medication with the following exceptions: inadequately treated nausea, vomiting or diarrhoea. For fatigue, if present at baseline, there had to be an increase of ≥2 grades electrolytes abnormalities that were corrected within 72 hours with treatment any haematologic AE related to the trial medication defined as follows: CTCAE grade ≥4 neutropenia lasting ≥ 7 days and/or complicated by infection, or CTCAE grade ≥4 thrombocytopenia, or CTCAE grade≥ 3 thrombocytopenia coupled with grade ≥ 2 of bleeding, or febrile neutropenia CTCAE grade 3 or higher. any other drug-related AE preventing the patient from taking his treatment according to the given schedule.	First treatment cycle (the first 21 days for Schedules A and B, the first 28 days for Schedule C).
Phase Ib: Number of Patients With DLTs Observed During the On-treatment Period	Number of patients with Dose Limiting Toxicities (DLTs) observed during the on-treatment period of Phase Ib is reported. The following drug related adverse events (AEs) qualified as DLT: any Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 non haematological toxicity considered related to trial medication with the following exceptions: inadequately treated nausea, vomiting or diarrhoea. For fatigue, if present at baseline, there had to be an increase of ≥2 grades electrolytes abnormalities that were corrected within 72 hours with treatment any haematologic AE related to the trial medication defined as follows: CTCAE grade ≥4 neutropenia lasting ≥ 7 days and/or complicated by infection, or CTCAE grade ≥4 thrombocytopenia, or CTCAE grade≥ 3 thrombocytopenia coupled with grade ≥ 2 of bleeding, or febrile neutropenia CTCAE grade 3 or higher. any other drug-related AE preventing the patient from taking his treatment according to the given schedule.	Date of the first administration of study treatment until date of the last administration of study treatment + 30 days residual effect period, up to 883 days.

Secondary Outcomes

Measure	Description	Time Frame
Phase Ia: Number of Patients With DLTs Observed During the On-treatment Period	Number of patients with DLTs observed during the on-treatment period of Phase Ia is reported. The following drug related adverse events (AEs) qualified as DLT: any Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 non haematological toxicity considered related to trial medication with the following exceptions: inadequately treated nausea, vomiting or diarrhoea. For fatigue, if present at baseline, there had to be an increase of ≥2 grades electrolytes abnormalities that were corrected within 72 hours with treatment any haematologic AE related to the trial medication defined as follows: CTCAE grade ≥4 neutropenia lasting ≥ 7 days and/or complicated by infection, or CTCAE grade ≥4 thrombocytopenia, or CTCAE grade≥ 3 thrombocytopenia coupled with grade ≥ 2 of bleeding, or febrile neutropenia CTCAE grade 3 or higher. any other drug-related AE preventing the patient from taking his treatment according to the given schedule.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

For all patients

Age 18 years or older at the time of signature of the informed consent.
Life expectancy of at least 12 weeks after the start of the treatment according to the investigator's judgement
Male or female patients. Women of childbearing potential* must be ready and able to use highly effective methods of birth control per ICH M3(R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information. For women of childbearing potential using a contraceptive pill, an additional barrier method is necessary due to the potential CYP3A4 inducing effect of BI894999. Male patients having a partner of childbearing potential must use condoms and ensure their partner is using a highly effective method of birth control as described above, during the trial and for at least three months after the end of the trial * Any female who has experienced menarche and does not meet the criteria for "women not of childbearing potential" as described below.

Women not of childbearing potential are defined as: women who are postmenopausal (12 months with no menses without an alternative medical cause) or who are permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy).

- Written informed consent consistent with ICH-GCP and local legislation

For patients with solid tumours

Patients with a histologically or cytologically confirmed diagnosis of an advanced unresectable and/or metastatic, malignant solid tumour, who have failed conventional treatment or for whom no therapy of proven efficacy exists, or who are not amenable to standard therapies
Age ≥ legal age to be adult for the given country at the time of signature of the informed consent. For NC patients, age 15 years or older at the time of signature of the informed consent ( in Germany and South Korea, only legally adult patients may be included
Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0 or 1 at the time of screening. A score of 2 is allowed for NUT carcinoma patients
Recovery of therapy-related toxicities from previous chemotherapy, tyrosine kinase inhibitors, hormone therapy, immunotherapy, antibodies, vaccine therapy, or radiotherapy to CTCAE ≤ grade 1 (with the exception of alopecia, peripheral sensory neuropathy grade 2)
Life expectancy of at least 12 weeks after the start of the treatment according to the investigator's judgement
Male or female patients. Women of childbearing potential* must be ready and able to use highly effective methods of birth control per ICH M3(R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information. For women of childbearing potential using a contraceptive pill, an additional barrier method is necessary due to the potential CYP3A4 inducing effect of BI894999. Male patients having a partner of childbearing potential must use condoms and ensure their partner is using a highly effective method of birth control as described above, during the trial and for at least three months after the end of the trial treatment
Written informed consent consistent with ICH-GCP and local legislation. For adolescent NC patients aged 15 years to < legal adult age, written assent of the patient and written informed consent of the parents (both or one according to national regulation) or legal guardian of the adolescent
Written informed consent for tumour biopsies in the escalation phase Ia
- Optional for those patients until extension of the MTD cohort,
- Optional for the patients in the extension of MTD cohort at the same time points as described below for the expansion phase. For these patients in the extension of the MTD cohort, if they have an accessible lesion for biopsy, they will be offered optional consent for tumour biopsies
In addition, all patients included in the expansion Phase Ib must:
Have been diagnosed with one of the four types of tumours selected:
- small cell lung cancer (SCLC)
- metastatic castrate resistant prostate cancer (mCRPC)
- colorectal cancer (CRC)
- NUT carcinoma (NC) (for which the "midline" origin is not a prerequisite)
Have failed conventional treatments or who are not amenable to standard therapies (per criterion 1) that specifically include for:
- SCLC: a platinum-based therapy (previous treatment with topotecan is not mandatory)
- mCRPC: a hormonal agent (abiraterone, enzalutamide, or apalutamide) and a taxane (docetaxel or cabazitaxel)
- CRC: fluoropyrimidine, oxaliplatin and irinotecan, bevacizumab for patients eligible to this treatment and an anti-epidermal growth factor receptor (EGFR) in RAS (Rat Sarcoma Virus) wild type metastatic CRC.
Have measurable disease (radiated lesions and lesions used for biopsy do not qualify as target lesions), according to RECIST 1.1 (R09-0262) (for NC patients only nonmeasurable disease is acceptable); or according to PCWG3 (R17-3377) for the mCRPC cohort (see point 5 of inclusion criteria below, specific to mCRPC patients)
Have progressive disease within the last 6 months, according to RECIST 1.1 (R09-0262) or according to PCWG3 (R17-3377) for the mCRPC cohort (see point 5 of inclusion criteria below, specific to mCRPC patients). NC patients do not need to show progression per RECIST 1.1 (for example, if newly diagnosed).
Have a tumour lesion accessible for biopsies (pre- and at steady state under treatment in Cycle 1, ideally from the same anatomic lesion) (except for mCRPC patients having only bone metastases or for patients with therapeutic INR because of treatment with a vitamin K antagonist or a novel oral anticoagulant. Biopsies are optional for NC patients
Give written informed consent for two tumour biopsies, one at screening and one after start of treatment, between Day 8 and Day 11 of Cycle 1 (or between day 3 and day 8 if the day of biopsy in Cycle 1 needs to be moved as explained in Section 3.1) (when applicable)
In addition, all patients in the mCRPC expansion cohort of Phase Ib must have:
Histologically or cytologically confirmed adenocarcinoma of the prostate
Radiographic evidence of metastatic prostate cancer (stage M1 or D2). Distant metastases evaluable by bone scan, CT scan, or MRI within 28 days before the start of study treatment.
PSA ≥ 5 ng/mL (if no measurable disease by RECIST 1.1)
Prior surgical or chemical castration with a serum testosterone of <50 ng/dL (< 1.7 nmol/L) by luteinizing hormone releasing level hormone (LHRH) agonist or antagonist, or by abiraterone or by enzalutamide or apalutamide. If the actual method of castration is LHRH agonist or antagonist, the patient must be willing to continue the use of LHRH agonist or antagonist during protocol treatment.
Progressive disease defined as at least one of the following:
- Progressive measurable disease: using conventional solid tumour criteria RECIST 1.1
- Bone scan progression: at least two new lesions on bone scan plus a rising PSA as described in point c below
- Increasing PSA level: at least two consecutive rising PSA values over a reference value (PSA no.1) taken at least 1 week apart. A third PSA (PSA no. 3) is required to be > than PSA no. 2; if not, a fourth PSA (PSA no. 4) is required to be > to PSA no. 2

In patients with DLBCL

Patients with histologically confirmed DLBCL who have failed 2 or more lines of systemic therapy including an anti-CD-20 therapy and an anthracycline or who are not amenable to standard therapies but have an indication for therapy as per investigator's judgement. Standard therapies may also include but are not limited to CAR-T cells therapy, depending on approved therapies in the country where the patient is treated
ECOG Performance Status 0, 1 or 2 at the time of screening
Measurable disease (radiated lesions do not qualify as target lesions) according to according to RECIL 2017 on the CT scan part of the FDG/PET-CT scan
Recovery of therapy-related toxicities from previous anti-lymphoma therapy to CTCAE <= grade 1 (with the exception of alopecia, peripheral sensory neuropathy grade 2)
written informed consent for tumour biopsies (optional)
Further inclusion criteria apply

Exclusion criteria:

For all patients:

Inability to swallow tablets
Additional other serious illness, concomitant non-oncological disease (e.g. active infectious disease including an active infection with SARS-CoV-2 confirmed by a PCR test or had one in the prior 6 weeks or active hepatitis (Hep) B infection as defined by positive Hep B DNA test, active Hep C infection as defined by positive Hep C RNA test and human immunodeficiency virus (HIV) infection (positive result in established HIV diagnostic assay), or ongoing toxicity from prior therapies considered by the investigator to potentially compromise patient's safety in this trial
Serum creatinine greater than 1.5 mg/dL (>132 µmol/L, SI unit equivalent)
Women who are pregnant, nursing, or who plan to become pregnant while in the trial
Treatment with other investigational drugs or participation in another clinical interventional trial within the past four weeks or within five times the half-life of the previous investigational drug, whichever is shorter, before start of therapy or concomitant with this trial
Patients unable to comply with the protocol
Patients who are actively abusing alcohol or drugs. Since no alcohol or drug testing is required per protocol, it is at the investigator's discretion to determine abuse.

For patients with solid tumours:

Additional other serious illness , concomitant non-oncological disease (e.g. active infectious disease or known chronic Hepatitis B/Hepatitis C infection and HIV), or ongoing toxicity from prior therapies considered by the investigator to potentially compromise patient's safety in this trial
History or presence of cardiovascular abnormalities deemed clinically relevant by the investigator such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to study entry.Left Ventricular Ejection Fraction (LVEF) less than 50% at baseline
Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the last 28 days before the start of treatment with BI 894999
Absolute neutrophil count less than 1500/mm^3
Platelet count less than 100 000/mm^3
Bilirubin greater than 1.5 mg/dL (>26 µmol/L, SI unit equivalent) (except known Gilbert's syndrome, accepted up to 2 mg/dL or up to 34.2 µmol/L in this case)
Aspartate amino transferase (AST) and/or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (if related to liver metastases, greater than five times the upper limit of normal)
Treatment with other investigational drugs or participation in another clinical interventional trial within the past four weeks (past two weeks for NC patients) or within five times the half-life of the previous investigational drug, whichever is the shorter, before start of therapy or concomitant with this trial
Systemic anti-cancer therapy within four weeks (past two weeks for NC patients) or five times the half-life of the drug, whichever is shorter. Radiotherapy given for curative intent or other than palliative radiotherapy within the past four weeks before start of therapy or concomitantly with this trial. This These restrictions does not apply to LHRH agonists or antagonists, steroids (given at a stable dose in the last four weeks) used for palliative intent, bisphosphonates, and denosumab and to palliative radiotherapy (no wash out required)

For patients with DLBCL:

Patient is eligible for curative salvage high dose therapy followed by stem cell transplant.
Primary central nervous system (CNS) lymphoma or known CNS involvement
Prior allogeneic bone marrow or stem cell transplant
High-dose therapy with stem cell support <3 months prior to visit 1
AST or ALT >2.5 x upper limit of normal (CTCAE grade 2 or higher)
Total bilirubin >1.5 x upper limit of normal (CTCAE grade 2 or higher)
Absolute neutrophil count <1.0 x 10^9/L(without growth factor support)
Platelets <100 x 10^9/L (without transfusions)
Significant concurrent medical disease or condition which according to the investigator's judgement would either compromise patient safety or interfere with the evaluation of the safety of the test drug, e.g. symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within 6 months prior to study entry, cardiac arrhythmia requiring therapy with the exception of extra systoles or minor conduction abnormalities
Chronic or ongoing infection requiring treatment at the time of enrolment or within the previous two weeks, e.g. active infectious disease or known Hepatitis B/Hepatitis C infection, HIV
Systemic anti-DLBCL therapy within the past two weeks or five times the half-life of the drug, whichever is shorter (palliative radiotherapy and agents used for palliative reasons for example steroids and bisphosphonates, are allowed)
Further exclusion criteria apply

Contacts/Locations Module

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Dana-Farber Cancer Institute		Boston	Massachusetts	02215	United States
Memorial Sloan-Kettering Cancer Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37556913	Derived	Schoffski P, Machiels JP, Rottey S, Sadrolhefazi B, Musa H, Marzin K, Awada A. Phase Ia dose-escalation trial with the BET protein inhibitor BI 894999 in patients with advanced or metastatic solid tumours. Eur J Cancer. 2023 Sep;191:112987. doi: 10.1016/j.ejca.2023.112987. Epub 2023 Jul 11.

Label	URL
Related Info	View source

IPD Sharing Statement Module

For Phase Ib - Schedule B SCLC, Phase Ib - Schedule B mCRPC, DMC decided on 28Nov2018 to lower the dose of SCLC and mCRPC due to safety concern, thus patients treated prior the decision received 2.5mg BI 894999 and patients treated after the decision received 2mg . For Phase Ib - Schedule C NC, the dose was lowered since DMC reclaimed the MTD as 6/3mg on 08Jul2020 after 1 patient already treated with 7/3.5mg, so the first patient in NC and all the following patients were treated with 6/3mg.

Arm/Group Information

ID	Title	Description
FG000	Phase Ia - Schedule A: 0.2 mg BI 894999	Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 0.2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule A was a continuous daily intake in cycles of 21 days.
FG001	Phase Ia - Schedule A: 0.5 mg BI 894999	Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 0.5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule A was a continuous daily intake in cycles of 21 days.
FG002	Phase Ia - Schedule A: 1 mg BI 894999	Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 1 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule A was a continuous daily intake in cycles of 21 days.
FG003	Phase Ia - Schedule A: 1.5 mg BI 894999	Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 1.5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule A was a continuous daily intake in cycles of 21 days.
FG004	Phase Ia - Schedule A: 2 mg BI 894999	Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule A was a continuous daily intake in cycles of 21 days.
FG005	Phase Ia - Schedule A: 5 mg BI 894999	Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule A was a continuous daily intake in cycles of 21 days.
FG006	Phase Ia - Schedule B: 1.5 mg BI 894999	Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 1.5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.
FG007	Phase Ia - Schedule B: 2 mg BI 894999	Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.
FG008	Phase Ia - Schedule B: 2.5 mg BI 894999	Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 2.5 mg of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.
FG009	Phase Ia - Schedule C: 5/2.5 mg BI 894999	Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 5 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 2.5 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.
FG010	Phase Ia - Schedule C: 6/3 mg BI 894999	Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 6 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 3 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.
FG011	Phase Ia - Schedule C: 7/3.5 mg BI 894999	Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 7 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 3.5 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.
FG012	Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL Patients)	Adult patients with histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) were administered orally 1.5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.
FG013	Phase Ia - Schedule B: 2 mg BI 894999 (DLBCL Patients)	Adult patients with histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) were administered orally 2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.
FG014	Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL Patients)	Adult patients with histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) were administered orally 2.5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.
FG015	Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL Patients)	Adult patients with histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 4 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 2 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.
FG016	Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL Patients)	Adult patients with histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 5 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 2.5 mg of BI 894999, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.
FG017	Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (SCLC Patients)	This arm included adult patients diagnosed with small cell lung cancer (SCLC). SCLC patients were initialy administered 2.5 mg of BI 894999. BI 894999 administration was performed in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water according to Schedule B (continuous intake for 14 days followed by one week off treatment in cycles of 21 days). The Data Monitoring Committee decided on 28 November 2018 to lower the 2.5 mg BI 894999 dose due to safety concerns to 2mg, therefore patients treated before the decision were administered 2.5mg, and patients treated after the decision were administered 2mg.
FG018	Phase Ib - Schedule B: 2.5 mg BI 894999 (CRC Patients)	Adult patients diagnosed with colorectal cancer (CRC) were administered orally 2.5 milligram (mg) of BI 894999. BI 894999 administration was performed in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water according to Schedule B (continuous intake for 14 days followed by one week off treatment in cycles of 21 days).
FG019	Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (mCRPC Patients)	This arm included adult patients diagnosed with metastatic castrate resistant prostate cancer (mCRPC). MCRPC patients were initialy administered 2.5 mg of BI 894999. BI 894999 administration was performed in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water according to Schedule B (continuous intake for 14 days followed by one week off treatment in cycles of 21 days). The Data Monitoring Committee decided on 28 November 2018 to lower the 2.5 mg BI 894999 dose due to safety concerns to 2mg, therefore patients treated before the decision were administered 2.5mg, and patients treated after the decision were administered 2mg.
FG020	Phase Ib - Schedule B: 2.5 mg BI 894999 (NC Patients)	Adult patients diagnosed with NUT carcinoma (NC) were administered orally 2.5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days. The 2.5 mg dose could be reduced to 2 mg in case of adverse events.
FG021	Phase Ib - Schedule C: 6/3 or 7/3.5 mg BI 894999 (NC Patients)	This arm included adult patients diagnosed with NUT carcinoma (NC). The DMC reclaimed the maximum tolerated dose (MTD) as 6/3mg on 08 July 2020 after 1 patient was already treated with 7/3.5mg, so the first patient in NC and all the following patients were treated with 6/3mg. Patients in were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 6 milligram (mg) of BI 894999, followed by six days intake of the maintenance dose of 3 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C).

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0002 subjects FG0012 subjects FG0023 subjects FG0036 subjects FG0046 subjects FG0052 subjects FG0066 subjects FG0076 subjects FG00813 subjects FG0094 subjects FG01015 subjects FG01112 subjects FG0128 subjects FG0134 subjects FG0142 subjects FG0152 subjects FG0162 subjects FG01712 subjects FG01814 subjects FG01911 subjects FG02020 subjects FG02122 subjects
COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
NOT COMPLETED		FG0002 subjects FG0012 subjects FG0023 subjects FG0036 subjects FG004

Type	Comment	Reasons
Progressive disease		FG0002 subjects FG0012 subjects FG0023 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Phase Ia - Schedule A: 0.2 mg BI 894999	Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 0.2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule A was a continuous daily intake in cycles of 21 days.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	Phase Ia: Number of Patients With DLTs Observed in the First Cycle	Number of patients with Dose Limiting Toxicities (DLTs) observed in the first treatment cycle of Phase Ia is reported. The following drug related adverse events (AEs) qualified as DLT: any Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 non haematological toxicity considered related to trial medication with the following exceptions: inadequately treated nausea, vomiting or diarrhoea. For fatigue, if present at baseline, there had to be an increase of ≥2 grades electrolytes abnormalities that were corrected within 72 hours with treatment any haematologic AE related to the trial medication defined as follows: CTCAE grade ≥4 neutropenia lasting ≥ 7 days and/or complicated by infection, or CTCAE grade ≥4 thrombocytopenia, or CTCAE grade≥ 3 thrombocytopenia coupled with grade ≥ 2 of bleeding, or febrile neutropenia CTCAE grade 3 or higher. any other drug-related AE preventing the patient from taking his treatment according to the given schedule.	Maximum Tolerated Dose (MTD) Evaluation Set (MTDS): Included all patients in the treated set (TS) of Phase 1a who were not replaced for the MTD determination.	Posted		Count of Participants		Participants		First treatment cycle (the first 21 days for Schedules A and B, the first 28 days for Schedule C).

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase Ia - Schedule A: 0.2 mg BI 894999	Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 0.2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule A was a continuous daily intake in cycles of 21 days.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Boehringer Ingelheim, Call Center	Boehringer Ingelheim	1-800-243-0127		clintriage.rdg@boehringer-ingelheim.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 24, 2020	Nov 4, 2022	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Jan 19, 2022	Nov 4, 2022	SAP_001.pdf

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D009369	Neoplasms

Intervention Browse Module

ID	Term
C000630920	BI 894999

Masking Info

Phase Ia - Schedule A: 1.5 mg BI 894999

Phase Ia - Schedule A: 2 mg BI 894999

Phase Ia - Schedule A: 5 mg BI 894999

Phase Ia - Schedule B: 1.5 mg BI 894999

Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)

Phase Ia - Schedule B: 2 mg BI 894999

Phase Ia - Schedule B: 2 mg BI 894999 (DLBCL patients)

Phase Ia - Schedule B: 2.5 mg BI 894999

Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)

Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients)

Phase Ia - Schedule C: 5/2.5 mg BI 894999

Phase Ia - Schedule C: 6/3 mg BI 894999

Phase Ia - Schedule C: 7/3.5 mg BI 894999

Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)

Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (SCLC patients)

Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (mCRPC patients)

Phase Ib - Schedule B: 2.5 mg BI 894999 (CRC patients)

Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)

Phase Ib - Schedule C: 6/3 or 7/3.5 mg BI 894999 (NC patients)

EG0000 affected2 at risk

EG0010 affected2 at risk

EG0020 affected3 at risk

EG0030 affected6 at risk

EG0040 affected6 at risk

EG0050 affected2 at risk

EG0060 affected6 at risk

EG0070 affected6 at risk

EG0080 affected13 at risk

EG0090 affected4 at risk

EG0100 affected15 at risk

EG0112 affected12 at risk

EG0121 affected8 at risk

EG0131 affected4 at risk

EG0140 affected2 at risk

EG0150 affected2 at risk

EG0160 affected2 at risk

EG0170 affected3 at risk

EG0180 affected9 at risk

EG0190 affected14 at risk

EG0200 affected10 at risk

EG0210 affected1 at risk

EG0220 affected20 at risk

EG0231 affected21 at risk

EG0240 affected1 at risk

EG0000 affected2 at risk

EG0011 affected2 at risk

EG0020 affected3 at risk

EG0031 affected6 at risk

EG0041 affected6 at risk

EG0050 affected2 at risk

EG0062 affected6 at risk

EG0072 affected6 at risk

EG0084 affected13 at risk

EG0090 affected4 at risk

EG0105 affected15 at risk

EG0116 affected12 at risk

EG0121 affected8 at risk

EG0130 affected4 at risk

EG0141 affected2 at risk

EG0151 affected2 at risk

EG0161 affected2 at risk

EG0171 affected3 at risk

EG0180 affected9 at risk

EG0193 affected14 at risk

EG0209 affected10 at risk

EG0211 affected1 at risk

EG02211 affected20 at risk

EG0236 affected21 at risk

EG0240 affected1 at risk

OG017NA± NAAUC0-24 could not be provided to reduce the risk of patient re-identificaton.

OG016NA± NACmax could not be provided to reduce the risk of patient re-identificaton.

OG017NA± NACmax could not be provided to reduce the risk of patient re-identificaton.

OG005NA± NAAUCτ, ss could not be provided to reduce the risk of patient re-identificaton.

OG014NA± NAAUCτ, ss could not be provided to reduce the risk of patient re-identificaton.

OG015NA± NAAUCτ, ss could not be provided to reduce the risk of patient re-identificaton.

OG016NA± NAAUCτ, ss could not be provided to reduce the risk of patient re-identificaton.

OG018NA± NAAUCτ, ss could not be provided to reduce the risk of patient re-identificaton.

OG005NA± NACmax, ss could not be provided to reduce the risk of patient re-identificaton.

OG014NA± NACmax, ss could not be provided to reduce the risk of patient re-identificaton.

OG015NA± NACmax, ss could not be provided to reduce the risk of patient re-identificaton.

OG016NA± NACmax, ss could not be provided to reduce the risk of patient re-identificaton.

OG018NA± NACmax, ss could not be provided to reduce the risk of patient re-identificaton.

OG0047.8(4.0 to 13.0)