Comparing 3 approaches for breast cancer

Inclusion

• +Participants with a known severe hypersensitivity to PD-1/PD-L1 inhibitors or Dato-DXd.
• +PD-L1 positive TNBC based on results from an appropriately validated investigational PD-L1 (22C3) assay (CPS ≥ 10) from a sponsorSponsorThe organisation responsible for the study overall.Read more → designated central laboratory.
• +Participants with a history of previously treated neoplastic spinal cord compression or treated, clinically inactive brain metastases that are no longer symptomatic, who require no treatment with corticosteroids or anticonvulsants, may be included in the study if they have recovered from acute toxic effects of radiotherapy.
• +\- Participants with treated clinically inactive brain metastases that are no longer symptomatic, who require no treatment with corticosteroids or anticonvulsants, may be included in the study if they have recovered from acute toxic effects of radiotherapy.
• +Active or uncontrolled hepatitis B or C virus infection.
• +Known HIV infection that is not well controlled.
• +Histologically or cytologically documented locally recurrent inoperable, which cannot be treated with curative intent, or metastatic TNBC, as defined by the ASCO-CAP guidelines.
• +ECOG PS 0 or 1.
• +Participants are expected to provide an FFPE tumour sample collected from a locally recurrent inoperable or metastatic tumour. Alternatively, an archival FFPE tumour sample can be submitted; it must have been collected ≤ 3 years prior to the participant signing informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more → (screeningScreeningThe checks done before joining, to see whether a study fits.Read more → start).
• +\- Patients with recurrent disease will be eligible if they have completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months have elapsed between completion of treatment with curative intent and the first documented recurrence.
• +Measurable disease as per RECIST 1.1.
• +Adequate bone marrow reserve and organ function.
• +Key Exclusion CriteriaExclusion criteriaThe things that would prevent someone from taking part.Read more →
• +As judged by investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →, any evidence of diseases (such as severe or uncontrolled medical conditions including systemic diseases, uncontrolled hypertension, serious gastrointestinal conditions associated with diarrhoea, chronic diverticulitis or previous complicated diverticulitis, history of allogeneic organ transplant, and active bleeding diseases, ongoing and active infection, significant cardiac conditions, substance abuse, psychiatric illness/social situation or psychological conditions) which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocolProtocolThe detailed plan a study must follow.Read more →.
• +History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before Cycle 1 Day 1 and of low potential risk for recurrence.
• +Uncontrolled infection requiring IV antibiotics, antivirals or antifungals.
• +Uncontrolled or significant cardiac disease.
• +Clinically severe pulmonary function compromise.
• +Clinically significant corneal disease.
• +Active or prior documented autoimmune or inflammatory disorders.
• +Any concurrent anti-cancer treatment.
• +Male and female participants of childbearing potential must agree to use protocol-specified method(s) of contraception.
• +Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning to become pregnant.
• +No prior chemotherapy or other systemic anti-cancer therapy for metastatic or locally recurrent inoperable breast cancer.
• +Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin).
• +History of non-infectious ILD/pneumonitis (including radiation pneumonitis) that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
• +Prior exposure to any treatment including ADC containing a chemotherapeutic agent targeting topoisomerase I and TROP2-targeted therapy.