NCT04938817

Who might be able to join this trial:

• You have been confirmed (through a tissue or cell sample test) to have extensive-stage small cell lung cancer (a type of lung cancer that has spread) and need a second round of treatment.
• Your cancer got worse during or after your first treatment, which included a type of immunotherapy drug (one that targets PD-1 or PD-L1) combined with platinum-based chemotherapy.
• Your cancer is classified as Stage IV (the most advanced stage, meaning it has spread to other parts of the body).
• You have only had one previous course of treatment for your small cell lung cancer.
• If you are a woman who could become pregnant, you must have a negative pregnancy test taken within 24 hours (urine test) or 72 hours (blood test) before starting the study treatment.
• Your cancer can be measured on scans (such as CT scans), confirmed by two separate assessments.
• You are able to provide either a stored tumor tissue sample or a newly taken biopsy from a tumor that has not been previously treated with radiation.
• Your general health and ability to carry out daily activities is rated as good (a score of 0 or 1 on a standard medical scale), checked within 7 days before being assigned to the trial.
• If you have hepatitis B, you must have been on antiviral treatment for at least 4 weeks and have no detectable virus in your blood before joining.
• If you have a history of hepatitis C, the virus must be undetectable in your blood at screening.
• Your doctors expect you to live for more than 3 months.
• Your blood pressure is well controlled (at or below 150/90 mmHg), with no changes to blood pressure medication in the week before joining, with or without medication.
• (For Arms A–D only) Male participants must either avoid sexual intercourse with women who could become pregnant or use contraception during treatment and for at least 7 days after the last dose of lenvatinib (one of the study drugs).
• (For Arms A–D only) Female participants who could become pregnant must not be pregnant or breastfeeding and must use effective contraception during treatment and for a set period after the last dose of the study drugs (up to 120 days depending on which drug was taken last).
• (For Arm E only) If you could produce sperm, you must agree not to donate sperm and to use contraception (or abstain from relevant sexual activity) during treatment and for 150 days after the last dose.
• (For Arm E only) If you could become pregnant, you must use highly effective contraception during treatment and for 210 days after the last dose, and agree not to donate or store eggs during this time.

Who may not be able to join:

• You have had any other cancer treatment (including experimental treatments) within the past 4 weeks.
• You have had radiation therapy within the past 2 weeks, or radiation to the lungs above a certain dose within the past 6 months.
• You have received a live vaccine (such as some flu or travel vaccines) within the past 30 days.
• You have another cancer (besides small cell lung cancer) that is still active or has needed treatment within the past 3 years.
• You have active cancer that has spread to the brain and is causing symptoms or is growing — though people with small, stable, treated brain metastases may still be considered (confirm with trial site).
• You have had a severe allergic reaction (grade 3 or higher) to any of the study drugs or their ingredients.
• You have an active autoimmune disease (where your immune system attacks your own body) that has needed treatment with medication in the past 2 years, other than simple hormone or steroid replacement therapy.
• You have an active infection that is being treated with medication.
• (For Arms A–D only) You have had major surgery within the past 3 weeks.
• (For Arms A–D only) You have a pre-existing severe fistula (an abnormal connection between organs or tissues, grade 3 or higher).
• (For Arms A–D only) You have had a serious heart or major blood vessel problem in the past 12 months, such as heart failure, unstable chest pain, heart attack, stroke, or a dangerous irregular heartbeat.
• *(For Arms A–