Inclusion Criteria:

- Subjects must provide signed, written informed consent.

- Subjects must be ≥18 years of age.

- Subjects must have Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or
1.

- Subjects must have histologically or cytologically confirmed diagnosis of cancer.

- Subjects must have advanced solid malignancies without an established standard of
care therapy option OR progression following the most recent therapy.

- Subjects may have measurable lesion(s) according to RECIST criteria.

- Subjects with stable CNS metastases or leptomeningeal involvement are eligible only
if they are not taking oral steroids or CYP450 enzyme-inducing anticonvulsants.

- Subjects must have a LVEF ≥ 50% or ≥ lower limit of normal for the institution based
on MUGA scan or ECHO. The same method of cardiac evaluation must be used
consistently throughout the study.

- Subjects in the expanded cohort phase must have archived tumor tissue samples
available for biomarker analysis. It is preferable that a paraffin-embedded tissue
block from archived tumor tissue from the primary tumor be submitted.

- Subjects must provide informed consent and blood samples to the pharmacogenetics
research.

- Subjects must be able to swallow and retain oral medications.

- Subjects must have adequate hematological, hepatic, and renal function as defined:
Hematologic: absolute neutrophil count (ANC) ≥1.5 X 10^9/L, hemoglobin ≥10 g/dL,
platelets ≥100 X 10^9/L; Hepatic: serum bilirubin≤ upper limit of normal (ULN), AST
and ALT ≤ 5 x ULN if documented liver metastases, AST and ALT ≤ 3 X ULN without liver
metastases; Renal: calculated creatinine clearance ≥50 mL/min.

- A female is eligible to enter and participate in this study if she is of:

- Non-childbearing potential (i.e., women with functioning ovaries who have a current
documented hysterectomy, or bilateral tubal ligation, or women who are
post-menopausal defined as documented absence of menses for > 12 months or women with
a documented bilateral oophorectomy);

- Childbearing potential (i.e. women with functioning ovaries and no documented
impairment of oviductal or uterine function that would cause sterility.) This
category includes women with oligomenorrhoea (severe), women who are perimenopausal,
and young women who have begun to menstruate. These subjects must have a negative
serum pregnancy test at Screening (≤7 days prior to administration of first dose of
investigational product), and agree to use adequate contraception beginning at least
2 weeks prior to the first does of investigational product and for 28 days after the
final dose of investigational product. GSK acceptable contraceptive methods, when
used consistently and in accordance with both the product label and the instructions
of the physician, are as follows:

- An intrauterine device with a documented failure rate of less than 1% per year.

- Vasectomized partner who is sterile prior to the female subject's entry and is the
sole sexual partner for that female.

- Complete abstinence from sexual intercourse for 14 days before exposure to
investigation product, through the clinical trial, and for at least 28 days after the
last dose of investigational product.

- Double-barrier contraception (condom with spermicidal jelly, foam suppository, or
film; diaphragm with spermicide; or male condom and diaphragm with spermicide).

- Oral contraceptives are not reliable due to potential drug-drug interaction.

- Male subjects with a female partner of childbearing potential are eligible to enter
and participate in the study if they practice adequate barrier methods of
contraception (see above) or abstinence during the study from the first dose of
investigational product until 3 months after the final dose of investigational
product.

Exclusion Criteria:

- Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to the first dose of investigational product or
who have unresolved or unstable, serious toxicity from prior administration of
another investigational drug and/or of prior cancer treatment.

- Subjects who have received an investigational drug within 30 days or 5 half-lives
(whichever is longer) preceding the first dose of investigational product.

- Subjects taking prohibited medications listed in the protocol.

- Subjects with a known immediate or delayed hypersensitivity or untoward reaction to
topotecan or other related compounds, or to drugs chemically related to lapatinib.
These include other anilinoquinazolines, such as gefitinib, erlotinib, or other
chemically-related compounds.

- Subjects with presence of uncontrolled infection.

- Subjects with malabsorption syndrome, disease significantly affecting
gastrointestinal function, or resection of the stomach or small bowel.

- Subjects with uncontrolled or symptomatic angina, arrhythmias.

- Subjects with Class II to IV heart failure as defined by the New York Heart
Association (NYHA) functional classification system.

- Women who are pregnant or lactating.

- Subjects who have received an allogeneic bone marrow transplant.

- Subjects with any serious and/or unstable pre-existing medical, psychiatric, or other
conditions that could interfere with subject's safety, obtaining informed consent or
compliance to the study.

- Subjects with psychological, familial, sociological, or geographical conditions that
do not permit compliance with the protocol.

- Subjects with clinical history, current alcohol or illicit drug use which, in the
judgment of the investigator, would interfere with the subject's ability to comply
with the dosing schedule and protocol-specified evaluations.

- Subjects with current active hepatic or biliary disease (with exception of patients
with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic
liver disease per investigator assessment).