Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT07205822 | A Study of Dato-DXd in Inoperable or Metastatic Hormone Receptor-positive, HER2 IHC 0 Breast Cancer | PHASE3 | RECRUITING | 100 | — | — | Oct 30, 2025 | Feb 2, 2028 | May 12, 2026 | 40 | United States, China +4 |
| NCT06103864 | A Phase III Study of Dato-DXd With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer | PHASE3 | RECRUITING | 625 | — | — | Nov 23, 2023 | Sep 30, 2030 | Apr 30, 2026 | 316 | United States, Argentina +22 |
| NCT06112379 | A Phase III Randomised Study to Evaluate Dato-DXd and Durvalumab for Neoadjuvant/Adjuvant Treatment of Triple-Negative or Hormone Receptor-low/HER2-negative Breast Cancer | PHASE3 | ACTIVE NOT_RECRUITING | 1,902 | — | — | Nov 14, 2023 | Sep 23, 2032 | Apr 2, 2026 | 283 | United States, Australia +24 |
| NCT05629585 | A Study of Dato-DXd With or Without Durvalumab Versus Investigator's Choice of Therapy in Patients With Stage I-III Triple-negative Breast Cancer Without Pathological Complete Response Following Neoadjuvant Therapy (TROPION-Breast03) | PHASE3 | ACTIVE NOT_RECRUITING | 1,174 | — | — | Nov 28, 2022 | Jan 30, 2030 | Mar 18, 2026 | 276 | United States, Belgium +15 |
| NCT05374512 | A Study of Dato-DXd Versus Investigator's Choice Chemotherapy in Patients With Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy (TROPION-Breast02) | PHASE3 | ACTIVE NOT_RECRUITING | 644 | — | — | May 16, 2022 | Dec 31, 2026 | May 15, 2026 | 228 | United States, Argentina +21 |
| NCT05104866 | A Phase-3, Open-Label, Randomized Study of Dato-DXd Versus Investigator's Choice of Chemotherapy (ICC) in Participants With Inoperable or Metastatic HR-Positive, HER2-Negative Breast Cancer Who Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy (TROPION-Breast01) | PHASE3 | ACTIVE NOT_RECRUITING | 732 | — | — | Oct 18, 2021 | Jul 31, 2026 | May 5, 2026 | 167 | United States, Argentina +18 |
PFS is defined as time from date of first dose of study intervention until progression per RECIST 1.1 as assessed by the investigator or death due to any cause.
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. The comparison will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anticancer therapy or clinically progresses prior to RECIST 1.1 progression. However, if the participant progresses or dies immediately after 2 or more consecutive missed visits, the participant will be censored at the time of the latest evaluable assessment prior to the 2 missed visits. The measure of interest is the HR of PFS.
EFS is defined as the time from the date of randomisation until the date of the first occurrence of any of the following events: disease progression precluding surgery, disease recurrence (local, regional, distant, or contralateral), second primary invasive cancer (other than squamous or basal cell skin cancer), or relapse from prior malignancy, or death by any cause (in the absence of recurrence). Non-invasive breast cancers and positive margins in the surgical sample do not count as an event for EFS. EFS will be determined by the investigator based on all available clinical assessments. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy. The measure of interest will be the Hazard Ratio of EFS.
iDFS is defined as time from randomisation until date of first occurrence of one of the following events: ipsilateral invasive breast tumour (local) recurrence, regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and skin of ipsilateral breast), or distant recurrence (metastatic breast cancer that has either been biopsy-confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; second primary non-breast invasive cancer (other than squamous or basal cell skin cancer); or death from any cause. iDFS will be determined based on disease recurrence per investigator assessment based on all available clinical assessments. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anticancer therapy. The measure of interest will be the HR (hazard ratio) of iDFS for Dato-DXd + durvalumab vs ICT.
OS is defined as the time from randomisation until the date of death due to any cause. The analysis will include all randomised participants, by treatment group as randomised. The measure of interest is the hazard ratio \[HR\] of OS.
PFS is defined as time from randomization until progression per RECIST 1.1, as assessed by BICR, or death due to any cause. The analysis will include all randomized participants as randomized regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy, or clinically progresses prior to RECIST 1.1.
OS is defined as time from randomization until the date of death due to any cause. The comparison will include all randomized participants as randomized, regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy. The measure of interest is the hazard ratio of OS.
| Arm | Type | Description |
|---|---|---|
| single arm group | EXPERIMENTAL | All participants will receive Dato-DXd (6 mg/kg IV on Day 1, Q3W; up to a maximum of 540 mg Q3W for participants ≥ 90 kg) until investigator-defined disease progression according to RECIST 1.1 or until unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met. |
| Dato-DXd + durvalumab | EXPERIMENTAL | Arm 1: Dato-DXd + durvalumab |
| Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab | ACTIVE_COMPARATOR | Arm 2: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin) |
| Dato-DXd | EXPERIMENTAL | Arm 3: Dato-DXd |
| Dato-DXd plus durvalumab | EXPERIMENTAL | Participants receive durvalumab every 3 weeks (Q3W) + Dato-DXd Q3W as neoadjuvant therapy prior to surgery; followed by 9 cycles of durvaluamb 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: 1. 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); 2. Doxorubicin (Q3W) or epirubicin (Q3W) + cyclophosphamide (Q3W) for 4 cycles (12 weeks) followed by paclitaxel (weekly) for 4 cycles (12 weeks); 3. Carboplatin (weekly or Q3W) + paclitaxel (weekly) for 4 cycles (12 weeks); 4. Capecitabine (Q3W) for 8 cycles. |
| Pembrolizumab plus chemotherapy | ACTIVE_COMPARATOR | Participants receive pembrolizumab every 3 weeks (Q3W) + paclitaxel weekly + carboplatin (weekly or Q3W) x 4 cycles, followed by pembrolizumab Q3W + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 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. |
| Dato-DXd in combination with Durvalumab | EXPERIMENTAL | Arm 1: Dato-DXd 6 mg/kg IV Q3W x 8 cycles + Durvalumab 1120 mg IV Q3W x 9 cycles |
| Investigators Choice Therapy | ACTIVE_COMPARATOR | Arm 3: Capecitabine (1000 or 1250 mg/m2 oral BID on Days 1 to 14, Q3W) for 8 cycles Pembrolizumab\* (200 mg IV on Day 1, Q3W) for 9 cycles Capecitabine (1000 or 1250 mg/m2 oral BID on Days 1 to 14, Q3W) for 8 cycles + pembrolizumab\* (200 mg IV on Day 1, Q3W) for 9 cycles \* Only participants who have received prior pembrolizumab in the neoadjuvant setting should receive pembrolizumab as part of their adjuvant therapy on Arm 3. |
| Investigator's Choice of Chemotherapy (ICC) | ACTIVE_COMPARATOR | Arm 2: If no prior taxane, or prior taxane in the (neo)adjuvant setting and DFI \> 12 months, paclitaxel or nab-paclitaxel If prior taxane and DFI ≤ 12 months: capecitabine, carboplatin, or eribulin. |
| Investigators Choice of Chemotherapy (ICC) | ACTIVE_COMPARATOR | Arm 2: ICC Capecitabine Gemcitabine Eribulin mesylate Vinorelbine |
| Name | Type | Description |
|---|---|---|
| Dato-DXd | DRUG | All participants will receive Dato-DXd (6 mg/kg IV on Day 1, Q3W; up to a maximum of 540 mg Q3W for participants ≥ 90 kg) until investigator-defined disease progression according to RECIST 1.1 or until unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met. Continued treatment with the same study drug post-progression may be allowed, based on prior discussion with sponsor/sponsor representative/study physician on a case-by-case basis following written investigator's confirmation of continuing clinical benefit to the patient post progression. The study is anticipated to enrol for an 18-month period, and DCO is expected to occur approximately 6 months after the last participant has been dosed. |
| Durvalumab | DRUG | Provided in 500mg vials. IV infusion. Experimental drug. |
| Paclitaxel | DRUG | IV infusion. Active comparator. |
| Nab-paclitaxel | DRUG | IV infusion. Active comparator. |
| Gemcitabine | DRUG | IV infusion. Active comparator. |
| Carboplatin | DRUG | IV infusion. Active comparator. |
| Pembrolizumab | DRUG | IV infusion. Active comparator. |
| Doxorubicin | DRUG | IV infusion Experimental/Active Comparator |
| Epirubicin | DRUG | IV Infusion Experimental/Active Comparator |
| Cyclophosphamide | DRUG | IV infusion Experimental/Active Comparator |
| Capecitabine | DRUG | Tablet Oral route of administration Experimental/Active Comparator |
| Olaparib | DRUG | Tablet Oral route of administration Experimental/Active Comparator |
| Eribulin mesylate | DRUG | IV infusion. Active comparator |
| Eribulin | DRUG | IV Infusion. Active comparator |
| Vinorelbine | DRUG | IV Infusion. Active comparator |
Inclusion Criteria: 1. Participant must be ≥ 18 years (and above legal age) at the time of screening. 2. Inoperable or metastatic HR-positive, HER2 IHC 0 breast cancer (per ASCO/CAP guidelines, on local laboratory results); ie, is documented as HR-positive (either ER and/or PgR positive \[ER or PgR...