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 chemotherapy consisting of at least 4 cycles of platinum-etoposide plus either atezolizumab or durvalumab and have not received any other treatment (except for immunotherapy as maintenance treatment); the 60 day-interval is calculated from the date of the last chemotherapy administration to the date of the first radiologically documented progressive disease.
5. No previous radiotherapy on the only one site disease progression, unless that site had 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 off steroids or on a stable dose of steroids (≤10 mg of prednisone-equivalent) are also eligible. Radiotherapy must have been completed a minimum of 14 days prior to registration, 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 last menstrual period) before the screening visit, or are surgically sterile. If they are of childbearing potential, a negative serum pregnancy test prior to study entry has to be documented; furthermore, they agree to practice 2 effective methods of contraception, 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 true abstinence, when this is in line with the preferred and usual lifestyle of the subject.
9. For Males: even if surgically sterilized (i.e., post-vasectomy status) agree to practice effective barrier contraception during the entire study treatment period and 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 this criterion.
    * Total bilirubin \< 1.5x the institutional upper limit of normal (ULN)
    * Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 2.5x the institutional ULN (\< 5x if liver function test elevations are due to liver metastases)
    * Creatinine \< 1.5x institutional ULN or estimated creatinine clearance using the Cockcroft-Gault formula ≥ 30 mL/minute for patients with creatinine levels above institutional limits
    * For patients not receiving therapeutic anticoagulation: INR and aPTT ≤ 1.5 x ULN
    * Negative HIV test at screening {with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/μL, and have an undetectable viral load}
    * Negative hepatitis B surface antigen (HBsAg) test at screening
    * Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb 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 laboratory definition) hepatitis B virus (HBV) DNA testNegative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening The HCV RNA test must be performed for patients who have a positive HCV antibody test.
11. Stable medical condition, including the absence of acute exacerbations of chronic illnesses, 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 weeks before starting protocol treatment and patients have recovered from AEs related to radiotherapy 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 written informed consent. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical 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 of first-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 is required within 4 weeks prior to randomization)requiring immediate radiotherapy for palliation. 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 or whole brain radiotherapy and initiation of study treatment and recovery from AEs related to radiotherapy to ≤ grade 1 (except alopecia), or at least 28 days between 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., no metastases to the midbrain, pons, medulla or spinal cord);
   * There is no evidence of interim intracranial progression between completion of CNS 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 of second-line chemotherapy.
9. Patient has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines and COVID vaccines that do not contain live virus are permitted. Note: Patients, if enrolled, should not receive live vaccine whilst receiving 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-L1 inhibitor maintenance as part of first-line treatment.
11. Any condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of registration . The following are exceptions to this criterion:

    * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection);
    * Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent;
    * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
12. Diagnosed with or treated for another malignancy within 3 years before the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type may be enrolled in the study if they have undergone complete resection and no evidence of active disease is present.
13. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment other than those in the present study. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
14. Treatment with any other investigational agent within 30 days prior to starting study treatment, or concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an 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 and not fully recovered to baseline or to a stable clinical status. Insertion of a vascular device is allowed.
19. Patients who experienced medically significant or NCI CTCAE Grade 3 or higher toxicities in response to first-line immunotherapy
20. Unwilling or unable to comply with the protocol or cooperate fully with the investigator and site personnel.