BI 894999 First in Human Dose Finding Study in Advanced Malignancies

Inclusion criteria:

For all patients

- Age 18 years or older at the time of signature of the informed consent. For NUT
Midline Carcinoma (NMC) patients, age 15 years or older at the time of signature of
the informed consent (not applicable for Germany where only patients older than 18
years will be included)

- 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 solid tumour, who have failed conventional treatment or
for whom no therapy of proven efficacy exists, or who are not amenable to standard
therapies

- Eastern Cooperative Oncology Group performance score 0 or 1 at the time of screening

- Recovery of therapy-related toxicities from previous chemotherapy, tyrosine kinase
inhibitors, hormone therapy, immunotherapy, antibodies, vaccine therapy, or
radiotherapy to CTCAE < or =grade 1 (with the exception of alopecia, peripheral
sensory neuropathy grade 2)

- Written informed consent consistent with ICH-GCP and local legislation. For adolescent
NMC patients aged 15 to < 18 years 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

- optional for those patients until extension of the MTD cohort,

- or 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 (part 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) or NUT-midline carcinoma (NMC) (for which the "midline" origin is not a
prerequisite)

- Have a measurable disease (radiated lesions and lesions used for biopsy do not qualify
as target lesions), according to RECIST 1.1 (R09-0262) (for NMC patients only
non-measurable disease is acceptable); or according to PCWG3 (R17-3377) for the mCRPC
cohort

- have progressive disease within the last 6 months, according to RECIST 1.1 according
to PCWG3 for the mCRPC cohort

- 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 NMC
patients)

- give written informed consent to tumour biopsies, one at screening and one after start
of treatment, between Day 11 and Day 14 of Cycle 1 (when applicable)

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

- Second malignancy currently requiring another anti-cancer therapy

- 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)

- Systemic anti-cancer therapy within four weeks or five times the half-life of the
drug, whichever is shorter (for NMC patients, washout for monoclonal antibodies must
be discussed with the sponsor). 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