Summary
Eligible participants will be randomly allocated to one of two treatment arms.
In the Experimental Arm, participants will receive a regimen containing the antibody-drug conjugate called Datopotamab Deruxtecan (Dato-DXd) plus durvalumab immunotherapy, with or without chemotherapy.
Participants receive durvalumab (via IV infusion) + Dato-DXd (via IV infusion) every 3 weeks (Q3W) as neoadjuvant therapy prior to surgery; followed by 9 cycles of durvalumab (Q3W) as adjuvant therapy post-surgery.
Adjuvant chemotherapy may be given in combination with durvalumab only if participants have residual disease. Olaparib may be given for participants with gBRCA-positive tumours and residual disease.
Adjuvant chemotherapy may be one of these:
- Doxorubicin (Q3W) or epirubicin (Q3W) + cyclophosphamide (Q3W) for 4 cycles (12 weeks) followed by paclitaxel (weekly) and carboplatin (weekly or Q3W) for 4 cycles (12 weeks);
- Doxorubicin (Q3W) or epirubicin (Q3W) + cyclophosphamide (Q3W) for 4 cycles (12 weeks) followed by paclitaxel (weekly) for 4 cycles (12 weeks);
- Carboplatin (weekly or Q3W) + paclitaxel (weekly) for 4 cycles (12 weeks);
- Capecitabine (Q3W) for 8 cycles.
In the Active Comparator Arm, participants will receive pembrolizumab immunotherapy plus chemotherapy.
Participants will receive pembrolizumab (via IV Infusion) Q3W + paclitaxel (weekly) + carboplatin (weekly or Q3W) for 4 cycles, followed by pembrolizumab Q3W + (doxorubicin OR epirubicin) + cyclophosphamide Q3W for 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of pembrolizumab Q3W as adjuvant therapy post-surgery.
Adjuvant capecitabine (Q3W) for 8 cycles may be given in combination with pembrolizumab only if participants have residual disease. Olaparib may be given for participants with gBRCA-positive tumours and residual disease.