Biomarker Directed Trial of Temozolomide and PARP Inhibition 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 niraparib.
• Pregnant or breastfeeding.
• Subject with known hypersensitivity to niraparib components or excipients including tartrazine 9yellow #5) or any other study products are excluded.
• Subject with known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) are excluded.
• Participants have systolic BP >140 mmHg or diastolic BP >90 mmHg that has not been adequately treated or controlled.
• Any patient with prior history of Posterior Reversible Encephalopathy Syndrome (PRES).