Study to Evaluate GSK3052230 in Combination With Paclitaxel and Carboplatin, or Docetaxel or as Single Agent in Subjects With Solid Malignancies and Deregulated Fibroblast Growth Factor (FGF) Pathway Signaling

Inclusion Criteria

- Signed written informed consent

- Histologically or cytologically confirmed diagnosis: Arm A and B- stage IV recurrent
metastatic squamous NSCLC with Fibroblast growth factor receptor 1 (FGFR1) gene
amplification by central laboratory testing. Arm C- recurrent after local therapy or
unresectable MPM with measurable lesions.

For specific arms the following requirements:

Arm A: Subjects who have received no prior therapy for Stage IIIB or Stage IV or recurrent
metastatic disease. Note, to avoid any undue delay of initiating systemic chemotherapy for
these subjects with newly diagnosed metastatic disease, it is allowed to initiate the first
cycle of chemotherapy while eligibility for the study is still being determined, as long as
the first dose of GSK3052230 is given no later than Cycle 2 Day 1 of chemotherapy. In
addition, subjects with Stage IIIB or Stage IV disease and recurrence after previous NSCLC
that has been treated with surgery and adjuvant chemotherapy or a radio- chemotherapy
regimen with curative intent are eligible, provided 6 months has passed since this
treatment ended.

Arm B: Subjects who have documented tumor progression (based on radiological imaging) or
intolerability after receiving at least one prior line of platinum containing combination
chemotherapy for Stage IIIB or Stage IV or recurrent metastatic disease. Note: Prior
treatment should not include docetaxel but may have included paclitaxel.

Arm C: Subjects who have received no prior systemic therapy for MPM.

- Availability of archival tumor tissue required for assessment of deregulated FGF pathway
signalling, but not limited to, FGFR1 amplification or FGF2 or FGFR1 expression. If
archival tissue is not available, a fresh biopsy is required. In Arms A and B, subjects
will be prospectively screened for FGFR1 gene amplification using a Fluorescence in situ
hybridization (FISH) assay for the dose expansion and the MTD/MFD cohorts only. For
inclusion in this study, based on the central laboratory testing, FGFR1 gene amplification
must meet one of the following criteria: a ratio of FGFR1/CEN 8 of >=2; or average number
of FGFR1 signals per tumor nucleus of >=6; or the percentage of tumor nuclei containing >=5
FGFR1 signals is >=50%.

In Arm C, FGF2 expression by IHC will be evaluated retrospectively in tissue samples by a
central laboratory and is not a requirement for study entry.

- Measurable disease per RECIST version 1.1 (Arm A and B) and modified RECIST for Arm C.

- Male or female >=18 years of age.

- Women of childbearing potential must have a negative serum pregnancy test within 7
days of first dose of study treatment and agree to use effective contraception, from
14 days prior to the first dose of study treatment, throughout the study, and for 6
months following the last dose of chemotherapy or 4 weeks after the last dose of
GSK3052230, whichever is latest. .

- Men with a female partner of childbearing potential must have either had a prior
vasectomy or agree to use effective contraception for at least 2 weeks prior to
administration of the first dose of study treatment and for at least 6 months after
the last dose of chemotherapy to allow for clearance of any altered sperm.

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 for Arm A and C
subjects and 0-2 for Arm B.

- French subjects: In France, a subject will be eligible for inclusion in this study
only if either affiliated to or a beneficiary of a social security category

- Must have adequate organ function as defined by the following baseline values:
Absolute neutrophil count >=1.5 x 10^9/Liter, Hemoglobin >=9 gram (g)/decilitre(dL),
Platelets >=100 x 10^9/L, Partial thromboplastin time (PTT) <=1.25 x upper limit of
normal (ULN), Albumin >=2.5 g/dL, Serum total bilirubin <=1.25 times ULN (for Arm B:
<=ULN ), Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) <=2.5
times ULN (for Arm B: <=1.5 times ULN), Serum Creatinine <=1.5 x ULN, Or Measured or
Calculated Creatinine Clearance >=45 mL/min (Arm A or B), >=65 mL/min (Arm C), Left
ventricular ejection fraction >=50% by ECHO.

Exclusion Criteria

- For Arms A and C: Treatment with any FGFR inhibitor. For Arm B: Treatment with any
anti-cancer therapy (for biological anti-cancer therapies see criteria below) during
the preceding 4 weeks or within 4 half-lives of the therapy, whichever is longer.

- Receipt of any biological therapy within 6 weeks of the first dose of GSK3052230

- Unresolved toxicity of National Cancer Institute Common Terminology Criteria for
Adverse Events, version 4.03 (NCI CTCAE version 4.03) Grade 2 or higher from previous
anti-cancer therapy, except alopecia.

- Active malignancy other than the cancer under study. Subjects with a history of
completely resected non-melanomatous skin carcinoma or successfully treated in situ
carcinoma are eligible.

- Presence of uncontrolled infection

- Prior major surgery or trauma within 28 days before first dose of study drug

- Presence of any non-healing wound, fracture, or ulcer

- Any prohibited medication(s) as described in protocol

- Conditions likely to increase the potential for abdominal perforation or fistula
formation, including but not limited to:

Luminal intestinal cancers or bulky abdominal disease. Presence or history of abdominal
fistula, gastrointestinal perforation, peptic ulcer disease or intra-abdominal abscess
within the six months prior to the first dose of GSK3052230.

Other risk factors for perforation, such as acute diverticulitis, obstruction or previous
abdominal or pelvic radiation.

- Symptomatic leptomeningeal or brain metastases or spinal cord compression Note:
Subjects previously treated for these conditions are eligible if they meet both of the
criteria below: (1) have had stable CNS disease for at least 4 weeks after local
therapy as assessed by imaging (contrast enhanced magnetic resonance imaging [MRI] or
computed tomography [CT]) prior to Day 1, and (2) are asymptomatic and off
corticosteroids, or are on stable dose of corticosteroids for at least 4 weeks prior
to Day 1.

- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to study drugs (GSK3052230, docetaxel, paclitaxel, carboplatin,
pemetrexed, cisplatin) and or their excipients that contraindicate their
participation.

- Known human immunodeficiency virus-positive serology, acquired immunodeficiency
syndrome (AIDS), or an AIDS-related illness.

- Prior organ or allogeneic stem cell transplant

- The following cardiac abnormalities:

Corrected QT (QTc) interval >=480 millisecond. History of acute coronary syndromes
(including unstable angina) within the past 24 weeks Coronary angioplasty or stenting
within the past 24 weeks. Class II, III, or IV heart failure as defined by the New York
Heart Association (NYHA) functional classification system.

Abnormal cardiac valve morphology (>= Grade 2) documented by echocardiogram (subjects with
Grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study).

History of known arrhythmias (except sinus arrhythmia and atrial fibrillation that is
controlled) within the past 24 weeks.

- Presence or history of hemoptysis (>1/2 teaspoon of red blood) 2 weeks prior to the
first dose of GSK3052230

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

- Current active liver or biliary disease (with the exception of Gilbert's syndrome or
asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease
per investigator's assessment).

- Pregnant, lactating or actively breast feeding females.

- French subjects: The French subject has participated in any study using an
investigational study treatment(s) during the previous 30 days.