First-in-Human Dose Escalation Trial in Subjects With Advanced Malignancies

Inclusion Criteria:

- Age greater than or equal to (>=)18 years

- Confirmed diagnosis of advanced malignancies that may be controlled with p70S6K or Akt
inhibition based on already identified molecular alteration known to affect the PAM
pathway, such as:: such as: such as: phosphate and tensin homolog (PTEN),
phosphoinositide 3-Kinase catalytic subunit alpha isoform (PIK3CA), protein kinase B 1
(Akt 1), Akt 3, mammalian target of rapamycin (mTOR), tumor sclerosis complex 1
(TSC1), tumor sclerosis complex 2 (TSC2), in subjects who have received at least all
treatment options considered to be standard therapy, unless some available treatment
are not acceptable to the subject. For the dose escalation portion of the trial,
subjects must have received the standard therapy unless intolerant or contraindicated.

- Part 2, Cohort 1: For subjects with only PAM pathway alterations, subjects must
have only PAM alterations, excluding Akt2 activating mutations or amplifications,
and no other genomic alterations.

- Part 2, Cohort 2: Histologically confirmed local laboratory testing
(immunohistochemistry 3+ staining and/or fluorescence in situ hybridization ratio
>= 2.0) HER2+ metastatic breast cancer subjects who are resistant to
trastuzumab-containing treatment and progressed on trastuzumab, pertuzumab, a
taxane, and/or trastuzumab emtansine. There is no limit regarding the number of
prior lines of therapy. Subjects may be enrolled regardless of whether or not
their tumor harbors a PAM pathway alteration (documentation of PAM pathway
alteration for this cohort is not required).

- Part 2, Cohort 3: Histologically and/or cytologically confirmed diagnosis of
breast cancer with hormone receptor-positive status (ER and/or PgR positive) and
HER2-negative status with prior exposure to tamoxifen and/or an aromatase
inhibitor and/or an aromatase inhibitor plus palbociclib. Prior treatment with
tamoxifen in the neoadjuvant setting is allowed but must have been discontinued
for at least 1 year prior to the first dose.

- Measurable disease using clinically appropriate criteria for the type of malignancy,
RECIST version 1.1 for solid tumors and Cheson 2007 for lymphoma

- A tumor accessible for biopsies and consent to undergo tumor biopsies before and
during MSC2363318A treatment. Subjects who do not have a tumor suitable for biopsy
(such as, but not limited to, high procedural risk, inaccessible site for needle
biopsy, etc.) but are otherwise eligible for this study may be considered for
enrollment on a case-by-case basis after discussion with the Medical Monitor of the
study

- Ability to read and understand the informed consent form and willingness and ability
to give informed consent and demonstrate comprehension of the trial before undergoing
any trial activities

- Negative blood pregnancy test at the screening visit for women of childbearing
potential

- Willingness to avoid pregnancy and breast feeding beginning two weeks before the first
MSC2363318A dose and ending three months after the last trial treatment. Male subjects
with female partners of childbearing potential and female subjects of childbearing
potential must use adequate contraception in the judgment of the Investigator, such as
a two barrier method or a one barrier method with spermicide or intrauterine device
during trial treatment dosing and for 3 months after the last dose of the study.

Exclusion Criteria:

- Eastern Cooperative Oncology Group Performance Status >=2

- Previous therapy with:

- Chemotherapy, immunotherapy, biologic therapy, or any other anticancer therapy
within 2 weeks (or five elimination half lives for noncytotoxics, whichever is
shorter) of Day 1 of trial drug treatment (6 weeks for nitrosureas or mitomycin).
Subjects on therapy with trastuzumab (trastuzumab cohort) may continue with
trastuzumab during the screening phase of the study. Subjects on endocrine
therapy may continue with antihormonal therapy until Day 1 of the study.

- Any investigational agent within 3 weeks of Day 1 of trial drug treatment

- Extensive prior radiotherapy on more than 30 percent of bone marrow reserves, or
prior bone marrow/stem cell transplantation within 5 years from enrolment

- Palliative radiation therapy within 2 weeks of Day 1 of trial drug treatment

- Known tumor EGFR, KRAS, and/or Akt2 mutations or amplification

- Ongoing toxicity due to a prior therapy, unless returned to baseline or Grade 1. Grade
2 toxicities (e.g., alopecia or peripheral neuropathy) that are not likely to increase
the subject's safety risk while receiving trial treatment may be accepted after
Sponsor approval.

- Major surgical intervention or participation in a therapeutic clinical trial within 28
days from Day 1 of the first dose of MSC2363318A

- Bone marrow impairment, renal impairment, liver function abnormality and impaired
cardiac function as defined in the protocol

- History of cerebral vascular accident or stroke within the previous 2 years

- Uncontrolled hypertension

- History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical
or biologic composition as MSC2363318A

- Known symptomatic central nervous system (CNS) metastases

- History of difficulty swallowing, malabsorption or other chronic gastrointestinal
disease or conditions that may hamper compliance and/or absorption of the
investigational product

- Known human immunodeficiency virus, viral hepatitis, or tuberculosis positivity

- Legal incapacity or limited legal capacity

- Any other condition which, in the opinion of the Investigator, might impair the
subject's tolerance of trial treatment, the safety of the individual subject or the
outcome of the trial. (including but not limited to: history of major depressive
episode, bipolar disorder, obsessive-compulsive disorder, schizophrenia, suicidal
attempt or ideation, homicidal ideation, or >= Common Terminology Criteria for Adverse
Events [CTCAE] Grade 3 anxiety)

- Immediate prior therapy with a PAM pathway inhibitor (i.e., the subject is excluded if
the last treatment regimen, prior to MSC2363318A, was a PAM pathway inhibitor, or if
the last PAM pathway inhibitor that the subject was treated with occured less than 2
months prior to Day 1 of trial drug treatment).