NCT05653752

Who might be able to join this trial:

• You are 18 years of age or older.
• You are well enough to carry out light activities and take care of yourself (your doctor can confirm this based on a standard health scale scored 0–2).
• Your blood counts, liver function, kidney function, and other lab results are within acceptable ranges (your doctor will check these — no blood transfusions or certain blood-boosting treatments within 14 days before starting).
• Your kidneys are filtering at an adequate level, measured by a standard calculation (confirm with trial site).
• Your blood clotting results are within an acceptable range (or, if you take blood thinners, within the range your doctor considers safe).
• You are expected to live for at least 3 more months.
• You are able and willing to attend all required visits and follow the study schedule.
• You have signed a consent form agreeing to take part after being fully informed about the trial.
• If you have non-small cell lung cancer (NSCLC): Your cancer has been confirmed by a tissue or cell sample, is advanced or has spread, and cannot be cured by surgery or radiation; you have a specific gene change (EGFR mutation — exon 19 deletion or L858R) confirmed from a tumor or, in some cases, a blood sample; and you have already been treated with a third-generation EGFR-targeted drug (such as osimertinib), at least one platinum-based chemotherapy, and (if treated in the US) an immune checkpoint drug, unless your doctor felt that treatment was not appropriate for you.
• If you have breast cancer (BC): Your cancer has been confirmed by a tissue or cell sample, is advanced or has spread, cannot be surgically removed, and is hormone receptor-positive and HER2-negative (confirmed by standard testing); you have already received at least one hormonal therapy combined with a CDK4/6 inhibitor, and have had no more than four chemotherapy regimens (including antibody-drug treatments) for advanced disease.
• You have at least one measurable tumor that can be tracked on scans, according to standard criteria.
• You are willing to provide a tumor tissue sample (either stored from a previous biopsy or a new one) for testing; if this is not possible, you may still be considered after discussion with the trial team.
• If you could become pregnant: You agree to use a highly effective form of contraception, and not to donate eggs, from the time of screening until at least 6 months after your last dose of the study drug.
• If you are male: You agree to use a highly effective form of contraception, and not to freeze or donate sperm, from the time of screening until at least 6 months after your last dose of the study drug.

Who may not be able to join:

• You have previously been treated with any therapy that specifically targets a protein called HER3 (including antibodies, antibody-drug treatments, or CAR-T therapies).
• You had a severe reaction (such as serious diarrhea) to a type of chemotherapy called a topoisomerase I inhibitor (examples include topotecan, irinotecan, or drugs containing DXd).
• You are currently enrolled in another clinical trial that involves a treatment (observational studies or follow-up-only participation may be acceptable — confirm with trial site).
• You have not waited long enough after your last cancer treatment before starting this trial (the required waiting periods vary depending on the type of treatment — your doctor will check this).
• You have had major surgery within 4 weeks before starting the trial, or are expected to need major surgery during the trial (diagnostic surgery may be acceptable — confirm with trial site).
• You have previously had a bone marrow transplant from a donor or received a transplanted organ.
• You have taken high-dose steroid tablets or other immune-suppressing medicines within 2 weeks before starting the trial (some exceptions apply, such as steroid inhalers, skin creams, or low-dose replacement therapy — confirm with trial site).
• You have received a live vaccine within 4 weeks before starting the trial, or plan to receive one during the trial.
• You have a history of cancer spreading to the lining around the brain and spinal cord (leptomeningeal carcinomatosis).
• You have cancer that has spread to the brain or is pressing on the spinal cord, unless it has been treated and has been