Biomarker Directed Trial of Temozolomide and Stenoparib in Relapsed SCLC

Prior treatment

• 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.
• Prior exposure to lurbinectedin, TMZ or stenoparib.

Other illness

• 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.)
• 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.

Lab values

• Subject with QTc interval 470 for females, or 450 for males per electrocardiogram (EKG) at screening.

Other

• Pregnant or breastfeeding.

• 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.