Biomarker Directed Trial of Temozolomide and Stenoparib in Relapsed SCLC

Inclusion Criteria:

* Age 18 years or older at the time of consent.
* Histological or cytological diagnosis of extensive-stage small cell lung cancer.
* Patients must have received one prior line of systemic therapy.

  * Patients must have received first-line therapy with Carboplatin and Etoposide.

    * If patient is re-treated with Carboplatin and Etoposide at least 6 months or more after first regimen, this will still be considered one line of
    * treatment and they will qualify for this trial.
  * Patients could have received immunotherapy in combination with the chemotherapy regimen.
  * Patients who have received Tarlatamab as second line treatment are allowed.
* ECOG Performance status 0-2.
* Measurable disease as per RECIST v1.1 (NOTE: Previously irradiated lesions are eligible as a target lesion only if there is documented progression of the lesion after irradiation).
* Adequate bone marrow, liver, and renal function, as assessed by the following laboratory requirements:

  * ANC 1.5
  * Platelets 100 × 109/L
  * Hemoglobin 9 g/dL or 5.6 mmol/L
  * Aspartate transaminase and alanine transaminase 2.5 × upper limit of normal (ULN), \<5× in patients with known liver metastases
  * Serum total bilirubin 1.5 × ULN, 1.5-3.0 × ULN may be included appropriate starting dose adjustment to 200 mg daily.
  * Creatinine \<1.5 × ULN or estimated glomerular filtration rate (GFR) 50 ml/min by Cockcroft-Gault. Depending on scenario, GFR 30-49 can be --permissible.
* Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test within 72 hours of cycle 1 Day 1.
* Male and female subjects of child-bearing potential must agree to use a double-barrier method of birth control from the screening visit through 180 days after the last dose of study drug.
* Male subjects of child-bearing potential must agree to use a double-barrier method of birth control including use a male condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak) and must agree to refrain from donating sperm from screening visit through at least 90 days after the last dose of study drug.
* Previously treated or asymptomatic brain metastases are allowed.

Exclusion Criteria:

* Unstable or clinically significant concurrent medical condition, psychiatric illness or social situation that would, in the opinion of the investigator, jeopardize the safety of a subject and/or their compliance with the protocol.
* Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy. (Suppressive therapy for chronic infections allowed, for example: Subjects with HIV/AIDS with adequate antiviral therapy to control viral load would be allowed. Subjects with viral hepatitis with controlled viral load would be allowed while on suppressive antiviral therapy.)
* Prior exposure to lurbinectedin, TMZ or stenoparib.
* Pregnant or breastfeeding.
* Clinical significant cardiovascular disease (ie active)
* Subject with known hypersensitivity to Stenoparib components
* Subject with known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) are excluded.
* Subject with QTc interval 470 for females, or 450 for males per electrocardiogram (EKG) at screening.