Eine klinische Studie zur Beurteilung von Durvalumab und Tremelimumab bei soliden Tumoren im fortgeschrittenen Stadium (STRONG)

Biological: MEDI4736 (Durvalumab);Biological: MEDI4736 (Durvalumab) + Tremelimumab

Inclusion criteria:

1. Must have a life expectancy of at least 12 weeks.

2. Age =18 years at the time of screening. For patients aged <20 years and enrolled in
Japan, a written informed consent should be obtained from the patient and his or her
legally acceptable representative

3. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol. Written informed consent and any locally required authorization (eg, Health
Insurance Portability and Accountability Act in the US, European Union [EU] Data
Privacy Directive in the EU) obtained from the patient/legal representative prior to
performing any protocol-related procedures, including screening evaluations. For
patients aged <20 years and enrolling in Japan, a written informed consent should be
obtained from the patient and his or her legally acceptable representative.

4. Disease not amenable to curative surgery

5. Eastern Cooperative Oncology Group (ECOG) performance status as defined in the
specific module.

6. Body weight >30 kg.

7. No prior exposure to anti-PD-1 or anti-PD-L1, including on another AstraZeneca study.
Exposure to other investigational agents may be permitted after discussion with the
Sponsor.

8. Adequate organ and marrow function as defined below

- Hemoglobin =9.0 g/dL

- Absolute neutrophil count =1.0 × 109 /L

- Platelet count =75 × 109/L

- Serum bilirubin =1.5 × the upper limit of normal (ULN). This will not apply to
patients with confirmed Gilbert's syndrome, who will be allowed in consultation
with their physician.

- ALT and AST =2.5 × ULN; for patients with hepatic metastases, ALT and AST =5 ×
ULN

- Measured creatinine clearance (CL) >40 mL/min or calculated creatinine clearance
(CL) >40 mL/min as determined by Cockcroft-Gault (using actual body weight)

Males:

Creatinine CL = Weight (kg) × (140 - Age) (mL/min) 72 × serum creatinine (mg/dL)

Females:

Creatinine CL = Weight (kg) × (140 - Age) x 0.85 (mL/min) 72 × serum creatinine
(mg/dL)

9. Female patients of childbearing potential (ie, not surgically sterile or post
menopausal) who are sexually active with a non sterilized male partner must use at
least one highly effective method of contraception from the time of screening and must
agree to continue using such precautions for 180 days after the last dose of
durvalumab + tremelimumab combination therapy or 90 days after the last dose of
durvalumab monotherapy (see Section 3.8 and specifically Table 1).

10. Evidence of post-menopausal status or negative urinary or serum pregnancy test (per
Section 4) for female pre-menopausal patients. Women will be considered
post-menopausal if they have been amenorrheic for 12 months without an alternative
medical cause. The following age-specific requirements apply:

11. Women <50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal treatments
and if they have luteinizing hormone and follicle- stimulating hormone levels in the
post-menopausal range for the institution or underwent surgical sterilization
(bilateral oophorectomy or hysterectomy).

Women =50 years of age would be considered post-menopausal if they have been amenorrheic
for 12 months or more following cessation of all exogenous hormonal treatments, had
radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced
menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral
oophorectomy, bilateral salpingectomy or hysterectomy).

Non sterilized male patients who are sexually active with a female partner of childbearing
potential must use a male condom plus spermicide from screening through 180 days after
receipt of the final dose of durvalumab + tremelimumab combination therapy or 90 days after
receipt of the final dose of durvalumab monotherapy.

Exclusion criteria:

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site).

2. Previous IP assignment in the present study.

3. Concurrent enrollment in another clinical study, or another sub-study of this
protocol, unless it is an observational (non-interventional) clinical study or during
the follow up period of an interventional study.

4. Participation in another clinical study with an investigational product during the
last 28 days or 5 half-lives, whichever is longer, prior to the first dose of study
treatment.

5. Any concurrent chemotherapy, investigational agent, biologic, or hormonal therapy for
cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions
(eg, hormone replacement therapy) is acceptable.

6. Local treatment of isolated lesions for palliative intent is acceptable (eg, local
surgery or radiotherapy).

7. Receipt of any investigational anticancer therapy within 28 days or 5 half-lives,
whichever is longer, prior to the first dose of study treatment.

8. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
radiation within 4 weeks of the first dose of study drug. Note: Local treatment of
isolated lesions, excluding target lesions, for palliative intent is acceptable.

9. Major surgical procedure (as defined by the Investigator) within 28 days prior to the
first dose of IP. Note: Local surgery of isolated lesions for palliative intent is
acceptable.

10. History of allogenic organ transplantation.

11. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, ILD, serious chronic GI conditions associated
with diarrhea, or psychiatric illness/social situations that would limit compliance
with study requirement, substantially increase risk of incurring AEs or compromise the
ability of the patient to give written informed consent

12. History of another primary malignancy except for

- Malignancy treated with curative intent and with no known active disease =5 years
before the first dose of investigational product (durvalumab + tremelimumab) and
of low potential risk for recurrence

- Adequately treated non-melanoma skin cancer or l