Atezolizumab and Rechallenge Chemotherapy in Relapsed Patients With Extensive-stage Small Cell Lung Cancer (ES-SCLC).

Inclusion Criteria:

1. Diagnosis of small-cell lung cancer (SCLC) (according to WHO classification 2015)confirmed at pathology (histology or cytology).

2. Male or female and ≥ 18 years of age.

3. Life expectancy ≥ 12 weeks.

4. Disease progression at least 60 days after the completion of first-line chemotherapyconsisting of at least 4 cycles of platinum-etoposide plus either atezolizumab ordurvalumab and have not received any other treatment (except for immunotherapy asmaintenance treatment); the 60 day-interval is calculated from the date of the lastchemotherapy administration to the date of the first radiologically documentedprogressive disease.

5. No previous radiotherapy on the only one site disease progression, unless that sitehad subsequent evidence of progressive disease.

6. Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2.

7. Patients with treated brain metastases (or untreated but asymptomatic) and offsteroids or on a stable dose of steroids (≤10 mg of prednisone-equivalent) are alsoeligible. Radiotherapy must have been completed a minimum of 14 days prior toregistration, and patients must have recovered from AEs related to radiotherapy to <grade 1 (except alopecia)

8. For Females: must be postmenopausal (defined as occurring 12 months after lastmenstrual period) before the screening visit, or are surgically sterile. If they areof childbearing potential, a negative serum pregnancy test prior to study entry hasto be documented; furthermore, they agree to practice 2 effective methods ofcontraception, at the same time, from the time of signing the informed consent form (ICF) through 5 months after the last dose of study drug,or agree to practice trueabstinence, when this is in line with the preferred and usual lifestyle of thesubject.

9. For Males: even if surgically sterilized (i.e., post-vasectomy status) agree topractice effective barrier contraception during the entire study treatment periodand through 6 months after the last dose of study drug, or practice true abstinence,when this is in line with the preferred and usual lifestyle of the subject.

10. Normal baseline laboratory values as specified below:

• Absolute neutrophil count (ANC) ≥1500/mm3

• Platelet count ≥ 100 x 109/L (≥100,000/μL) without transfusion

• Hemoglobin ≥ 90 g/L (≥ 9 g/dL); patients may be transfused to meet thiscriterion.

• Total bilirubin < 1.5x the institutional upper limit of normal (ULN)

• Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5xthe institutional ULN (< 5x if liver function test elevations are due to livermetastases)

• Creatinine < 1.5x institutional ULN or estimated creatinine clearance using theCockcroft-Gault formula ≥ 30 mL/minute for patients with creatinine levelsabove institutional limits

• For patients not receiving therapeutic anticoagulation: INR and aPTT ≤ 1.5 xULN

• Negative HIV test at screening {with the following exception: patients with apositive HIV test at screening are eligible provided they are stable onanti-retroviral therapy, have a CD4 count ≥ 200/μL, and have an undetectableviral load}

• Negative hepatitis B surface antigen (HBsAg) test at screening

• Positive hepatitis B surface antibody (HBsAb) test at screening, or negativeHBsAb at screening accompanied by either of the following:

• Negative total hepatitis B core antibody (HBcAb)

• Positive total HBcAb test followed by a negative (per local laboratorydefinition) hepatitis B virus (HBV) DNA testNegative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followedby a negative HCV RNA test at screening The HCV RNA test must be performedfor patients who have a positive HCV antibody test.

11. Stable medical condition, including the absence of acute exacerbations of chronicillnesses, serious infections, or major surgery within 4 weeks before registration,and otherwise noted in other inclusion/exclusion criteria.

12. Recovered (i.e., ≤ grade 1 toxicity) from effects of prior anticancer therapy,except alopecia.

13. Prior radiotherapy is allowed provided that it has been completed more than 2 weeksbefore starting protocol treatment and patients have recovered from AEs related toradiotherapy to < grade 1

14. Ability to comply with protocol requirements.

15. The patient or the patient's legal representative has to be able to provide writteninformed consent. Voluntary written consent must be given before performance of anystudy-related procedure not part of standard medical care, with the understandingthat consent may be withdrawn by the patient at any time without prejudice to futuremedical care.

Exclusion Criteria:

1. More than 1 line of prior treatment for ES-SCLC.

2. First-line treatment without either atezolizumab or durvalumab.

3. First-line chemotherapy other than platinum-etoposide.

4. Less than 4 cycles of first-line platinum-etoposide.

5. Presence of resistant relapse (progressive disease within 60 days from the end offirst-line chemotherapy) or refractory disease (progressive disease during the first 4 cycles of first-line chemoimmunotherapy).

6. Symptomatic brain metastases or spinal cord compression (CT or MRI of the head isrequired within 4 weeks prior to randomization)requiring immediate radiotherapy forpalliation. Patients with treated brain metastases (or untreated but asymptomatic)and off steroids or on a stable dose of steroids (≤10 mg of prednisone-equivalent)are also eligible provided that all of the following criteria are met:

• If treated, at least 14 days between the end of stereotactic radiotherapy orwhole brain radiotherapy and initiation of study treatment and recovery fromAEs related to radiotherapy to ≤ grade 1 (except alopecia), or at least 28 daysbetween neurosurgical resection and initiation of study treatment;

• Anticonvulsant therapy at a stable dose is permitted;

• Metastases are limited to the cerebellum or the supratentorial region (i.e., nometastases to the midbrain, pons, medulla or spinal cord);

• There is no evidence of interim intracranial progression between completion ofCNS directed therapy (if administered) and initiation of study treatment.

7. Evidence of leptomeningeal disease.

8. Any comorbid condition or unresolved toxicity that would preclude administration ofsecond-line chemotherapy.

9. Patient has received a live-virus vaccination within 30 days of planned treatmentstart. Seasonal flu vaccines and COVID vaccines that do not contain live virus arepermitted. Note: Patients, if enrolled, should not receive live vaccine whilstreceiving IP and up to 30 days after the last dose of IP.

10. Treatment with systemic immunostimulatory agents (including, but not limited to,interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment except for PD-L1inhibitor maintenance as part of first-line treatment.

11. Any condition requiring systemic treatment with either corticosteroids or otherimmunosuppressive medications within 14 days of registration . The following areexceptions to this criterion:

• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intraarticular injection);

• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day ofprednisone or its equivalent;

• Steroids as premedication for hypersensitivity reactions (e.g., CT scanpremedication).

12. Diagnosed with or treated for another malignancy within 3 years before the firstdose of study drug, or previously diagnosed with another malignancy and have anyevidence of residual disease. Patients with non-melanoma skin cancer or carcinoma insitu of any type may be enrolled in the study if they have undergone completeresection and no evidence of active disease is present.

13. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatmentother than those in the present study. Concurrent use of hormonal therapy fornon-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.

14. Treatment with any other investigational agent within 30 days prior to startingstudy treatment, or concurrent enrolment in another clinical study, unless it is anobservational (non-interventional) clinical study or during the follow-up period ofan interventional study.

15. Infection requiring intravenous antibiotic therapy or other serious infection within 14 days before the first dose of study drug.

16. Prior allogeneic stem cell or solid organ transplantation.

17. For female subjects: positive serum pregnancy test, pregnancy, or breastfeeding.

18. Surgery within 4 weeks (or 2 weeks for a minor surgery) before study enrolment andnot fully recovered to baseline or to a stable clinical status. Insertion of avascular device is allowed.

19. Patients who experienced medically significant or NCI CTCAE Grade 3 or highertoxicities in response to first-line immunotherapy

20. Unwilling or unable to comply with the protocol or cooperate fully with theinvestigator and site personnel.