Atezolizumab in combinazione con una singola frazione di 8 Gy di radioterapia per il trattamento del carcinoma polmonare non a piccole cellule avanzato e in oligoprogressione dopo chemioterapia e immunoterapia con un agente anti-PD-1: uno studio di fase II, multicentrico, a braccio singolo

Drug: Atezolizumab

Gender: All
Maximum age: N/A
Minimum age: 18 Years

Inclusion Criteria

1. Signed Informed Consent Form

2. Male or female aged = 18 years

3. Ability to comply with the procedures of the study protocol, in the investigator's
judgment

4. Histologically or cytologically confirmed diagnosis of metastatic (Stage IV) NSCLC as
per the American Joint Committee on Cancer (AJCC) 8th edition

5. No sensitizing EGFR mutation (L858R or exon 19 deletions), ALK fusion oncogene or ROS1
rearrangement detected

6. Progressing to one line of chemotherapy defined as follows:a) A platinum-doublet.

b) In case of patients being ineligible for platinum-containing regimens but otherwise
compliant with the other inclusion-exclusion criteria of the present study, at least
one line of mono-chemotherapy is required.

c) As an exception, patients with oligoprogression to anti PD-1 agents alone for whom
the investigator considers local treatment of metastases and continuation of
immunotherapy appropriate (i.e. would not be eligible for 2nd line treatment) may be
enrolled without a previous line of chemotherapy. In this case, approval by the
Project Leader is necessary.

7. Progressing to an anti-PD-1 agent, either associated to chemotherapy or as monotherapy
(e.g., pembrolizumab or nivolumab)

8. Life expectancy = 8 weeks

9. Patients with treated, asymptomatic central nervous system (CNS) metastases are
eligible, provided they meet all of the following criteria:

1. Measurable disease outside CNS.

2. Only supratentorial and cerebellar metastases allowed (i.e., no metastases to
midbrain, pons, medulla or spinal cord).

3. No ongoing requirement for corticosteroids as therapy for CNS disease;
anticonvulsants at a stable dose allowed.

4. No stereotactic radiation within 7 days or whole-brain radiation within 14 days
prior to initiating study treatment.

5. No evidence of interim progression between the completion of CNS-directed therapy
and the screening radiographic study.

6. Patients with new asymptomatic CNS metastases detected at the screening scan must
receive radiation therapy and/or surgery for CNS metastases. Following treatment,
these patients may then be eligible without the need for an additional brain scan
prior to initiating study treatment, if all other criteria are met, including
clinical confirmation of no evidence of interim disease progression

10. Measurable disease by RECIST v1.1. Previously irradiated lesions can only be
considered as measurable disease if disease progression has been unequivocally
documented at that site since radiation and the previously irradiated lesion is not
the only site of disease.

11. Oligoprogressive disease defined as follows:

1. A minimum of 1 and a maximum of 4 progressing lesions (with up to 3 total organs
and 3 lesions per organ, except skeletal lesions) as assessed by a Positron
Emission Tomography-Computed Tomography (PET-CT) scan (contrast enhanced).

2. Definition of progression is made by RECIST 1.1 criteria (new lesions or
increased pre-existing ones).

12. Adequate hematologic and end organ function, defined by the following laboratory
results obtained within 14 days prior to initiating study treatment:

a) Absolute neutrophil count = 1,500 cells/?L without granulocyte colony-stimulating
factor support b) White blood cell (WBC) counts > 2,500/?L c) Lymphocyte count >
500/?L d) Serum albumin > 2.5 g/dL e) Platelet count = 100,000/?L without transfusion
within 2 weeks of laboratory test used to determine eligibility f) Hemoglobin = 9.0
g/dL, patients may be transfused or receive erythropoietic treatment to meet this
criterion g) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and
alkaline phosphatase (ALK) = 2.5 ? ULN with the following exceptions: patients with
documented liver metastases: AST and/or ALT = 5 ? ULN; patients with documented liver
or bone metastases: ALK = 5 ? ULN.

h) Serum bilirubin = 1.5 ? ULN. Patients with known Gilbert's syndrome who have serum
bilirubin level = 3 ? ULN may be enrolled i) Serum creatinine = 1.5 ? ULN

13. For female patients of childbearing potential agreement to remain abstinent (refrain
from heterosexual intercourse) or to use highly effective form(s) of contraceptive
methods that result in a failure rate of < 1% per year when used consistently and
correctly during the treatment period and for at least 5 months after the last dose of
atezolizumab.

1. A woman is considered to be of childbearing potential if she is postmenarcheal,
has not reached a postmenopausal state (= 12 continuous months of amenorrhea with
no identified cause other than menopause), and has not undergone surgical
sterilization (removal of ovaries and/or uterus)

2. Examples of contraceptive methods with a failure rate of < 1% per year include
bilateral tubal ligation, male sterilization, and established, proper use of
hormonal contraceptives that inhibit ovulation (combined estrogen and progestogen
containing hormonal contraception, or progestogen-only hormonal contraception
associated with inhibition of ovulation together with another additional barrier
method always containing a spermicide), hormone-releasing intrauterine devices,
and copper intrauterine devices

3. The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not acceptable methods of
contraception.

4. Oral contraception should always be combined with an additional contraceptive
method because of a potential interaction with the study drug.

5. Women who are not postmenopausal (= 12 months of non-therapy-induced amenorrhea)
or surgically sterile must have a negative serum pregnancy test result within 14
days prior to initiation of study drug.

Exclusion criteria

Cancer-specific exclusion criteria

1. Patients with an ECOG Performance status >2

2. Active or untreated CNS metastases as determined by Computed Tomography (CT) or
magnetic resonance imaging (MRI) evaluation of the brain during screening and prior
radiographic assessments

3. Spinal cord compression not definitively treate