A Phase II, Multi-Center, Open-Label Study of Tremelimumab Monotherapy in Patients with Advanced Solid Tumors

Programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated
antigen 4 (CTLA-4) proteins are involved in tumore escape.
Treatment with agents targeting CTLA-4 or PD-1/PD-L1 has shown activity in
several tumor types, with a subset of patients deriving
meaningful and durable benefit.

There remains a significant unmet medical need for additional treatment options
for patients with urothelial bladder cancer, pancreatic cancer and
triple-negative breast cancer who have failed first-line chemotherapy. To date,
no standard therapy has been established for patients who recur or are
refractory to first-line therapy.

The objective of this clinical trial is to determine the efficacy of
tremelimumab (anti-CTLA-4) as monotherapy in patients with these tumors and to
determine the efficacy and safety of sequenced MEDI4736 (anti-PD-L1)
monotherapy or MEDI4736 + tremelimumab combination
therapy after confirmed progression on tremelimumab monotherapy or during
follow-up.

Determine the efficacy and safety (using objective response rate) of
tremelimumab in patients with advanced solid tumors (UBC, PDAC, TNBC).

This is an open-label, multi-center study to determine the efficacy and safety
of tremelimumab monotherapy in the treatment of different cohorts of patients
with selected advanced solid tumors. If eligible and at the discretion of the
Investigator, after confirmed disease progression on tremelimumab monotherapy
or during follow-up, patients will have the option of being sequenced to
MEDI4736 monotherapy or MEDI4736 + tremelimumab combination therapy, for up to
12 months or until disease progression.

* Tremelimumab monotherapy:
Tremelimumab 750 mg via intravenous (IV) infusion every 4 weeks (q4w) for 7
doses (cycles), then q12w for 2 additional doses (cycles), for up to a total of
12 months (9 doses [cycles] total)

*MEDI4736 monotherapy:
MEDI4736 1.5 g via IV infusion q4w for up to a total of 12 months (13 doses
[cycles])

* MEDI4736 + tremelimumab combination therapy
- Tremelimumab 75 mg via IV infusion q4w starting on Week 0, for up to 4 cycles
- MEDI4736 1.5 g via IV infusion q4w, starting on Week 0, for up to a total of
4 cycles, followed by MEDI4736 1.5 g via IV infusion q4w, starting on Week 16,
for up to a total of 8 months (9 additional doses [cycles])

On several days during the study patients will undergo the following
assessments: - anamnesis (at screening also medical history) - physical
examination - WHO performance status - vital signs (blood pressure, pulse,
respiratory rate, temperature) - length - weight - CT or MRI scan - ECG - blood
and urine assessments - tumor biopsy (if applicable) - pregnancy test

Related side effects reported in subjects receiving tremelimumab alone are:
diarrhea, itching, rash, fatigue, vomiting, nausea, decreased appetite,
headache, stomach pain, fever, inflammation of the large intestine.
Related and serious side effects reported in subjects receiving tremelimumab
alone are: diarrhea, vomiting, dehydration, inflammation of the large
intestine, nausea

The types of side effects seen with the 2 drugs given together and when
MEDI4736 is given alone are very similar. However, the chances of developing
any of the side effects, and the severity of the effect appears to be greater
when the 2 drugs are given together compared to when MEDI4736 is given on its
own.

Side effects reported in subjects receiving MEDI4736 and tremelimumab are:
diarrhea, rash, elevated levels of ALT and AST, hepatitis, feeling tired,
nausea, shortness of breath, decreased appetite, fever, cough, pain in muscles
and joints, vomiting, colitis, pneumonitis, hypothyroidism, hyperthyroidism,
renal function problems, problemen met het zenuwstelsel, pancreatitis,
hypophysitis, adrenal gland insufficiency, allergic reaction