Study of Oraxol and Pembrolizumab in Subjects With Advanced Solid Tumors

This is a two part study. The dose escalation part will enroll subjects with advanced solid
tumors for which pembrolizumab is an FDA-approved therapy, to determine the MTD and identify
the recommended phase 2 dose of paclitaxel administered as Oraxol in combination with
pembrolizumab. Upon determination of the phase 2 dose, the dose expansion part will enroll
subjects with advanced/metastatic urothelial, gastric/gastro-esophageal, or NSCLC into 3
independent cohorts/arms to further evaluate the activity and safety of the study treatment.

Inclusion Criteria:

- Able to understand and sign an informed consent form

- Age ≥18 years

- Dose Escalation: Histologically confirmed metastatic or unresectable solid tumors for
which pembrolizumab is an FDA-approved therapy

- Dose Expansion: Histologically confirmed diagnosis of advanced or metastatic
urothelial carcinoma, gastric/gastro-esophageal adenocarcinoma or NSCLC. NSCLC
patients with EGFR or ALK translocation must have previously progressed on
FDA-approved therapy for these aberrations (accounting for PD-1 expression in each
histologic subtype)

- Dose Expansion: Must have stable disease or progressed on previously failed anti-PD1
or anti-PD-L1 therapy

- Previously progressed on or become intolerant of at least 1 line of systemic
chemotherapy for metastatic or advanced disease

- Must have at least one measurable site of disease as defined as per RECIST v1.1
criteria

- ECOG Performance Status ≤1

- Must have adequate hematology, blood chemistry, liver function and renal function.

- Willing and able to comply with scheduled visits, treatment plan and laboratory tests

- No concurrent malignancy except curatively treated basal or squamous cell carcinoma of
the skin or carcinoma in situ of the cervix, breast, or bladder

- Subjects receiving warfarin who are otherwise eligible and who may be appropriately
managed with low molecular weight heparin, in the opinion of the Investigator, may be
enrolled in the study provided they are switched to low molecular weight heparin at
least 7 days prior to receiving study treatment.

- Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis)
OR agree to use a condom with spermicide and to not donate sperm during the study and
for at least 30 days following last dose of Oraxol

- Female subjects must be postmenopausal (>12 months without menses) or surgically
sterile (ie, by hysterectomy and/or bilateral oophorectomy) or must be using effective
contraception (ie, oral contraceptives, intrauterine device, double barrier method of
condom and spermicide) and agree to continue use of contraception for 30 days after
their last dose of assigned study treatment. Abstinence is also an acceptable form of
contraception.

- Subjects who are of childbearing potential must have a negative serum pregnancy test
at Screening and within 96 hours before Week 1 dosing.

- Willing to return for follow-up

- Willing to provide blood samples for correlative research purposes

- Life expectancy of at least 3 months

Exclusion Criteria:

- Subjects with history of prior treatment with taxanes (eg, paclitaxel, docetaxel,
cabazitaxel) in expansion cohorts only

- History of prior significant toxicity from anti-PD-1 or anti-PDL1 therapy requiring
discontinuation of treatment

- Subjects who have not recovered from recent anti-cancer therapy received.

- Current or prior use of immunosuppressive medication within 14 days before the first
dose of pembrolizumab.

- Vaccinated with live, attenuated vaccines within 28 days of the first dose of the
study drug

- Active or prior documented autoimmune or inflammatory disorders. The following are
exceptions to this criterion:

- Subjects with vitiligo or alopecia

- Subjects with hypothyroidism (eg, following Hashimoto's thyroiditis) stable on
hormone replacement therapy or psoriasis not requiring systemic treatment

- Subject has impairment of GI function or GI disease that may significantly alter the
absorption of study drugs (including gastric bypass surgery and total gastrectomy).
Subjects with partial gastrectomy may be included in the trial.

- Uncontrolled concurrent illness.

- Known or suspected diagnosis of human immunodeficiency virus (HIV) or chronic active
Hepatitis B or C, or cirrhosis.

- Clinically significant pulmonary illness resulting in Grade ≥2 hypoxia.

- Symptomatic or uncontrolled brain metastases requiring current treatment (less than 28
days from last cranial radiation or 28 days from last steroids use).

- Impaired cardiac function or clinically significant cardiac disease.

- Subjects with a healing or open wound

- Lack of recovery of prior AEs to Grade ≤1 severity (NCI CTCAE v4.03) (except alopecia)
due to medications administered prior to the first dose of the trial drugs.

- Any other condition or finding (including social situation) that in the opinion of the
Investigator may render the patient at excessive risk for treatment complications or
may not be able provide evaluable outcome information.

- Pregnant or breast-feeding women

- Known allergy to any of the formulation components of Oraxol (oral paclitaxel or
HM30181A) or