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Biomarker-directed temozolomide plus stenoparib versus lurbinectedin for relapsed small cell lung cancer

Biomarker Directed Trial of Temozolomide and Stenoparib in Relapsed SCLC

Phase1; Phase2 Interventional VA Office of Research and Development · NCT06681220

This trial tests whether adding the oral drug stenoparib to temozolomide works better than standard lurbinectedin for people with relapsed small cell lung cancer and whether a blood biomarker can help pick who will benefit.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment166 (estimated)
Ages18 Years and up
SexAll
SponsorVA Office of Research and Development Federal
Drugs / interventionsTarlatamab, chemotherapy, immunotherapy
Locations11 sites (Palo Alto, California and 10 other locations)
Trial IDNCT06681220 on ClinicalTrials.gov

What this trial studies

This is a randomized phase 2, multicenter trial with a safety lead-in that compares an oral combination of stenoparib plus temozolomide to standard lurbinectedin given in 21-day cycles for patients with relapsed small cell lung cancer. The safety lead-in uses three dose cohorts (3 participants each) to find the maximum tolerated dose of stenoparib, starting at 200 mg once daily, followed by a randomized phase 2 portion stratified by biomarker status. Investigators will test two unvalidated blood-based biomarkers to see if they predict sensitivity to the stenoparib plus temozolomide combination. The trial includes small initial safety cohorts (9 participants for the combination arm and 5 for the lurbinectedin safety arm) before enrolling larger numbers in the phase 2 comparisons.

Who should consider this trial

Good fit: Adults (18+) with extensive-stage relapsed or recurrent small cell lung cancer who received one prior systemic regimen (including first-line carboplatin plus etoposide), have ECOG 0–2, and measurable disease are eligible.

Not a fit: Patients with ECOG performance status greater than 2, those who have received multiple prior lines of therapy beyond the allowed prior treatments, or patients who lack the predictive blood biomarker may be unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could give some patients a more effective oral combination and allow doctors to use a blood test to select the best treatment.

How similar studies have performed: Early-phase work combining PARP-targeting approaches with temozolomide has shown signals of activity in small cell lung cancer, but using blood biomarkers to direct stenoparib therapy is largely untested.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Palo Alto, California and 10 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Relapsed Small Cell Lung CancerRecurrent Small Cell Lung CancerPhase 2Small Cell Lung CancerBiomarker
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.