Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Datopotamab Deruxtecan, IMP administration, DS-1062a, DATROWAY®
Dato-DXd · 20 trials · 24 indications
DFS is defined as the time from randomisation until disease recurrence (local urothelial tract, local non urothelial tract or distant) per RECIST 1.1 as assessed by Investigator, or death due to any cause. The analysis will include all randomised participants as randomised. All events will be included, regardless of whether the participant discontinues study treatment or receives another anti-cancer therapy. The measure of interest is the HR of DFS.
PFS is defined as the time from randomization until radiological progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR), or death due to any cause.
OS is defined as the time from randomization until the date of death due to any cause.
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.
The analysis will include all randomised participants as randomised. All events will be included, regardless of whether the participant withdraws from randomised therapy or receives another anti-cancer therapy. The measure of interest is the HR of DFS. Descriptive analyses of Dato-DXd in combination with rilvegostomig versus rilvegostomig monotherapy and rilvegostomig monotherapy versus SoC will be performed to assess contribution of components.
PFS is defined as the time from randomization to Blinded Independent Central Review (BICR)-assessed progression using RECIST v1.1 or death due to any cause, regardless of whether the participant withdraws from study therapy, receives other anti-cancer therapy, or clinical progression.
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression, in the following population: • TROP2 biomarker positive population The measure of interest is the HR of PFS. PFS by investigator will be reported as a sensitivity analysis.
OS is defined as the time from randomisation until the date of death due to any cause. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anti-cancer therapy, in the following population: • TROP2 biomarker positive population The measure of interest is the HR of OS.
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.
PFS is defined as time from randomisation until progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) as assessed by BICR, or death due to any cause.
OS is defined as the time from randomisation until the date of 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.
OS is defined as the time from randomisation until the date of death due to any cause.
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.
Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.
Overall Survival (OS) is defined as the time from randomization to death due to any cause.
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.
The intracranial objective response rate (iORR) is defined as the proportion of patients achieving a complete response (CR) or partial response (PR) according to the RANO-BM (Response Assessment in Neuro-Oncology Brain Metastases) criteria, as assessed by central review. The best overall CNS (central nervous system) response is determined based on a composite assessment of radiographical CNS target and non-target lesion responses, corticosteroid use, and clinical status.
Overall Response Rate (ORR) is defined as the proportion of participants with a Best Overall Response (BOR) of confirmed Complete Response (CR) or confirmed Partial Response (PR). As assessed by investigator per RECIST v1.1
Progression Free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first. As assessed by BICR per RECIST v1.1
Overall Survival (OS) is defined as the time from randomization to death due to any cause.
The number of participants with triple negative breast cancer (TNBC) with molecular residual disease (MRD) only recurrence, which is defined as ctDNA positivity without radiographically measurable recurrence, during post-surgery surveillance.
Proportion of participants who have a confirmed CR or confirmed PR, as determined by the investigator at local site per RECIST 1.1.
Number of patients with adverse events and with serious adverse events including abnormal clinical observations, abnormal Electrocardiogram (ECG) parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline.
Proportion of participants achieving a ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later.
PFS is defined as time from start of treatment until progression per RECIST 1.1 as assessed by the investigator or death due to any cause.
ORR is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Confirmed ORR is defined as the proportion of participants in each cohort who have a confirmed CR or confirmed PR, as assessed by ICR per RECIST 1.1.
DLTs, TEAEs, SAEs, AESIs, ECOG PS, vital sign measurements, standard clinical laboratory parameters (hematology, clinical chemistry, and urinalysis), ECG parameters, ECHO/MUGA scan findings, and ophthalmologic findings
| Arm | Type | Description |
|---|---|---|
| Arm 1: Dato-DXd + rilvegostomig | EXPERIMENTAL | Dato-DXd: 6 mg/kg IV Q3W for 9 cycles (approximately 6 months), can be extended based on Investigator assessment of tolerability up to 17 cycles or up to 1 year + rilvegostomig: 750 mg IV Q3W 17 cycles or up to 1 year whichever occurs first. |
| Arm 2: Dato-DXd monotherapy | EXPERIMENTAL | Dato-DXd: 6 mg/kg IV Q3W for 9 cycles (approximately 6 months), can be extended based on Investigator assessment of tolerability up to 17 cycles or up to 1 year. |
| Arm 3 (SoC): nivolumab or durvalumab or EV + pembrolizumab | ACTIVE_COMPARATOR | Either: Nivolumab: 240 mg IV Q2W OR 480 mg IV Q4W up to 1 year Or: Durvalumab: 1500 mg IV Q4W for 8 cycles (or at a dose of 20 mg/kg Q4W in participants who weigh ≤ 30 kg) Or: EV 1.25 mg/kg D1, D8 Q3W up to 6 cycles + pembrolizumab 200 mg IV Q3W up to 14 cycles or 400 mg IV Q6W up to 7 cycles. |
| Arm A: Datopotamab deruxtecan (Dato-DXd) monotherapy | EXPERIMENTAL | Participants in the Dato-DXd monotherapy group will receive Dato-DXd as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle. |
| Arm B: Docetaxel monotherapy | ACTIVE_COMPARATOR | Participants in the docetaxel monotherapy group will receive docetaxel as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle. |
| 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 + rilvegostomig | EXPERIMENTAL | Participants in the Dato-DXd in combination with rilvegostomig group will receive Dato-DXd and rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W). |
| Rilvegostomig | EXPERIMENTAL | Participants in the rilvegostomig monotherapy group will receive rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W). |
| Standard of Care (SoC) | ACTIVE_COMPARATOR | Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC). |
| Group 1: Dato-DXd + Osimertinib Combination Therapy | EXPERIMENTAL | Participants will receive Dato-DXd 6 milligrams per kilogram (mg/kg) as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of every 21-day cycle, and osimertinib 80 milligrams (mg) once daily (QD) orally, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or other discontinuation criterion is met. |
| Group 2: Dato-DXd Monotherapy | EXPERIMENTAL | Participants will receive Dato-DXd 6 mg/kg as IV infusion Q3W on Day 1 of every 21-day cycle, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or other discontinuation criterion is met. |
| Group 3: Platinum-based Doublet Chemotherapy | EXPERIMENTAL | Participants will receive pemetrexed 500 milligrams per meter square (mg/m2) in combination with carboplatin (AUC5) or cisplatin 75 mg/m2 as IV infusion Q3W for 4 cycles followed by pemetrexed maintenance 500 mg/m2 as IV infusion Q3W, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or another discontinuation criterion is met. |
| Arm 1: Datopotamab Deruxtecan in Combination With Rilvegostomig | EXPERIMENTAL | Participants in the Datopotamab Deruxtecan (Dato-DXd) in combination with Rilvegostomig group will receive Dato-DXd plus rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle. |
| Arm 2: Rilvegostomig Monotherapy | EXPERIMENTAL | Participants in the rilvegostomig monotherapy group will receive rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle. |
| Arm 3: Pembrolizumab Monotherapy | ACTIVE_COMPARATOR | Participants in the pembrolizumab group will receive pembrolizumab as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle. |
| 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 + Durvalumab + Carboplatin | EXPERIMENTAL | Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 1120 mg durvalumab plus carboplatin area under the curve \[AUC\] 5 mg/mL/minute. |
| Histologic-specific therapy | ACTIVE_COMPARATOR | Non-squamous NSCLC participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m2 pemetrexed plus either AUC 5 mg/mL/minute carboplatin or 75 mg/m2 cisplatin. Squamous NSCLC participants will be randomized to receive 200 mg of pembrolizumab plus 200 mg/m2 paclitaxel plus AUC 5 or 6 mg/mL/minute carboplatin. |
| 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. |
| Pembrolizumab + Datopotamab Deruxtecan (Dato-DXd) | EXPERIMENTAL | Participants will be randomized to receive 200 mg pembrolizumab followed by 6.0mg/kg Dato-DXd. |
| Pembrolizumb | ACTIVE_COMPARATOR | Participants will be randomized to receive 200 mg pembrolizumab. |
| Investigators Choice of Chemotherapy (ICC) | ACTIVE_COMPARATOR | Arm 2: ICC Capecitabine Gemcitabine Eribulin mesylate Vinorelbine |
| Single arm: pembrolizumab, datopotamab-deruxtecan, and carboplatin | EXPERIMENTAL | Study treatment: * INDUCTION: Pembrolizumab 200 mg IV Q3W; Datopotamab-Deruxtecan 6mg/kg IV Q3W; Carboplatin AUC 5 IV Q3W. * For four (4) cycles. * MAINTENANCE: Pembrolizumab 200 mg IV Q3W for 35 cycles; Datopotamab-Deruxtecan 6mg/ kg IV Q3W.\* * until disease progression or unacceptable toxicity. |
| Part A (Phase 2): Dato-DXd, 4 mg/kg with Platinum | EXPERIMENTAL | Participants will receive Dato-DXd in combination with platinum (carboplatin or cisplatin). The RP3D will be determined using data collected from Part A. |
| Part A (Phase 2): Dato-DXd, 6 mg/kg with Platinum | EXPERIMENTAL | Participants will receive Dato-DXd in combination with platinum (carboplatin or cisplatin). The RP3D will be determined using data collected from Part A. |
| Part B (Phase 3): Dato-DXd, RP3D with Platinum | EXPERIMENTAL | Participants will receive Dato-DXd at the RP3D in combination with platinum (carboplatin or cisplatin). |
| Part B (Phase 3): Gemcitabine with Platinum | ACTIVE_COMPARATOR | Participants will receive Gemcitabine in combination with platinum (carboplatin or cisplatin). |
| Patients with higher residual cancer burden | EXPERIMENTAL | Participants with stage II/III triple negative breast cancer (TNBC) and residual disease post-neoadjuvant therapy, particularly patients with higher residual cancer burden (RCB II/III), remain at high risk for developing recurrence. |
| Substudy-1A | EXPERIMENTAL | Dato-DXd will be evaluated as monotherapy |
| Substudy-2A | EXPERIMENTAL | Dato-DXd in combination with capecitabine will be evaluated |
| Substudy-2B | EXPERIMENTAL | Dato-DXd in combination with 5-FU will be evaluated |
| Substudy-3A | EXPERIMENTAL | Dato-DXd will be evaluated as monotherapy |
| Substudy-3C | EXPERIMENTAL | Dato-DXd will be evaluated in combination with prednisone/prednisolone |
| Substudy-4A | EXPERIMENTAL | Dato-DXd will be evaluated as monotherapy |
| Substudy-4C | EXPERIMENTAL | Dato-DXd in combination with carboplatin + bevacizumab followed by Dato-DXd + bevacizumab will be evaluated |
| Substudy-5A | EXPERIMENTAL | Dato-DXd will be evaluated as monotherapy |
| Substudy-6A | EXPERIMENTAL | Dato-DXd in combination with volrustomig (MEDI5752) will be evaluated |
| Substudy-6B | EXPERIMENTAL | Data-DXd in combination with rilvegostomig (AZD2936) will be evaluated |
| Substudy-6C | EXPERIMENTAL | Dato-DXd will be evaluated as monotherapy |
| Substudy-6D | EXPERIMENTAL | Dato-DXd in combination with carboplatin or cisplatin will be evaluated |
| Substudy-6E | EXPERIMENTAL | Dato-DXd in combination with rilvegostomig (AZD2936) will be evaluated |
| Substudy-7A | EXPERIMENTAL | Dato-DXd will be evaluated as monotherapy |
| DS-1062a 6.0 mg/kg | EXPERIMENTAL | Participants will receive 6.0 mg/kg of DS-1062a |
| Dato-DXd Arm | EXPERIMENTAL | This single-arm study consists of multiple cohorts, divided by indication. |
| Cohort 1 | EXPERIMENTAL | Datopotamab deruxtecan (Dato-DXd) + Durvalumab in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy |
| Cohort 2 | EXPERIMENTAL | Datopotamab deruxtecan (Dato-DXd) + Durvalumab in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy |
| Cohort 3 | EXPERIMENTAL | Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy |
| Cohort 4 | EXPERIMENTAL | Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy |
| Cohort 5 | EXPERIMENTAL | Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC |
| Cohort 6 | EXPERIMENTAL | Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC |
| Cohort 7 | EXPERIMENTAL | Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC |
| Cohort 8 | EXPERIMENTAL | Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC |
| Cohort 9 | EXPERIMENTAL | Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC |
| Cohort 10 | EXPERIMENTAL | Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC |
| Cohort 11 | EXPERIMENTAL | Datopotamab deruxtecan (Dato-DXd) + MEDI5752 in participants with treatment-naïve NSCLC |
| Cohort 12 | EXPERIMENTAL | Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC |
| Cohort 13 | EXPERIMENTAL | Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC |
| Cohort 14 | EXPERIMENTAL | Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with treatment-naïve NSCLC |
| Cohort 4A | EXPERIMENTAL | Datopotamab deruxtecan (Dato-DXd) + Durvalumab + carboplatin in participants with treatment-naïve NSCLC |
| Name | Type | Description |
|---|---|---|
| Dato-DXd | DRUG | Dato-DXd is an ADC comprised of a recombinant humanised anti-TROP2 IgG1 mAb, MAAP-9001a, which is covalently conjugated via a cleavable drug-linker, MAAA1162a (the complex of MAAA-1181a and a maleimide tetrapeptide linker), using thioether bonds to the topoisomerase I inhibitor DXd. |
| Rilvegostomig | DRUG | Rilvegostomig is a monovalent, bispecific, humanised, IgG1 mAb engineered with an Fc domain that carries a triple mutation (L234F/L235E/P331S) designed to reduce Fc-mediated effector functions. Rilvegostomig contains 2 distinct paratopes that bind to human TIGIT and PD-1 and inhibit binding to their respective immuno-suppressive ligands. |
| Durvalumab | DRUG | A fully human monoclonal antibody that blocks the PD-L1 checkpoint to restore anti-tumor T-cell activity. Durvalumab is approved for Muscle invasive bladder cancer (MIBC) as perioperative regime. |
| Nivolumab | DRUG | A fully human monoclonal antibody against PD-1, promoting anti-tumor immunity. Approved across many malignancies such as melanoma, NSCLC, renal cell carcinoma, Hodgkin lymphoma, hepatocellular carcinoma, and colorectal cancer (dMMR/MSI-H), often alone or with ipilimumab. It's used in several cancers, notably unresectable stage III non-small cell lung cancer after chemoradiation and extensive-stage small cell lung cancer in combination regimens, among others, and is also approved for patients with muscle-invasive urothelial carcinoma (MIUC) at high risk of recurrence in the adjuvant setting. |
| Pembrolizumab | DRUG | A humanized monoclonal antibody targeting PD-1, enhancing T-cell-mediated immune responses against tumors. Indications span multiple cancers including melanoma, NSCLC, head and neck squamous cell carcinoma, urothelial carcinoma, MSI-H/dMMR tumors, and more. |
| Enfortumab vedotin | DRUG | An antibody-drug conjugate (ADC) comprised of a fully human anti-Nectin-4 IgG1 monoclonal antibody, linked via a protease-cleavable maleimide-based linker to the microtubule-disrupting agent monomethyl auristatin E (MMAE), which is conjugated through thioether bonds. Upon binding to Nectin-4-expressing cells, the ADC is internalized and releases MMAE, leading to disruption of microtubule dynamics and subsequent tumor cell death. Enfortumab vedotin is approved in urothelial cancers. |
| Datopotamab deruxtecan (Dato-DXd) | DRUG | Dato-DXd administered intravenously (IV) |
| Docetaxel | DRUG | Docetaxel administered intravenously (IV) |
| Datopotamab Deruxtecan | DRUG | Datopotamab Deruxtecan IV (intravenous) |
| Carboplatin | DRUG | Carboplatin IV (intravenous), Active Comparator |
| Cisplatin | DRUG | Cisplatin IV (intravenous), Active Comparator |
| Etoposide | DRUG | Etoposide IV (intravenous), Active Comparator |
| Pemetrexed | DRUG | Pemetrexed IV (intravenous), Active Comparator |
| Vinorelbine | DRUG | Vinorelbine IV (intravenous), Active Comparator |
| UFT | DRUG | UFT Oral route of administration, Active Comparator |
| Osimertinib | DRUG | Osimertinib will be administered orally. |
| Paclitaxel | DRUG | IV infusion. Active comparator. |
| Nab-paclitaxel | DRUG | IV infusion. Active comparator. |
| Gemcitabine | 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 |
| Circulating tumor DNA (ctDNA) testing | DIAGNOSTIC_TEST | Circulating tumor DNA (ctDNA) testing is a type of biopsy that analyzes fragments of DNA shed by cancer cells into the bloodstream. These fragments, known as ctDNA, can provide valuable information about the genetic makeup of a tumor without needing a traditional tissue biopsy. |
| 5-Fluorouracil | DRUG | Administered as an IV |
| Volrustomig | DRUG | Administered as an IV |
| Bevacizumab | DRUG | Administered as an IV |
| Prednisone/ prednisolone | DRUG | Administered orally |
| DS-1062a | DRUG | DS-1062a will be administered as an intravenous (IV) infusion once every 3 weeks |
| AZD2936 | DRUG | Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle |
| MEDI5752 | DRUG | Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle |
| AZD7789 | DRUG | Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle |
Inclusion criteria: 1. Participant must be \> 18 years of age at the time of signing the ICF. 2. Histologically confirmed MIUC of the bladder or upper tract. 3. Completed R0 radical resection 28 to 120 days before randomisation, with negative margins and no residual or metastatic disease. 4. Pathol...
Dato-DXd is an investigational antibody-drug conjugate being studied in several cancers: breast cancer, high-risk muscle invasive urothelial carcinoma, metastatic non-small cell lung cancer, and urothelial cancer. It is in Phase 3 development and is not yet approved. Clinical trials are enrolling adults across multiple countries in North America, Europe, and Asia.
Dato-DXd is an antibody-drug conjugate, a targeted oncology modality that delivers a therapeutic payload to cancer cells. It is being evaluated in biomarker-selected patient populations, including HER2 IHC 0 breast cancer and EGFR-mutated non-small cell lung cancer. The studies use active-controlled designs comparing Dato-DXd regimens against standard-of-care treatments.
Dato-DXd is being developed by AstraZeneca PLC, which trades under the ticker AZN. The company is running the clinical development program, which includes six active trials spanning Phase 2 and Phase 3 studies in breast cancer, urothelial carcinoma, and non-small cell lung cancer.
Dato-DXd is in Phase 3 clinical development. It is investigational and has not been approved by the FDA. The program includes multiple Phase 3 trials plus a Phase 2 study, all currently active, with a combined planned enrollment of more than 5,000 participants across the studies.
Dato-DXd is being studied in six active trials. These include NCT07720284 in high-risk muscle invasive urothelial carcinoma, NCT07205822 in HER2 IHC 0 breast cancer, NCT07129993 in locally advanced or metastatic urothelial carcinoma, and NCT06417814 in EGFR-mutated metastatic non-small cell lung cancer. All are recruiting or active and not recruiting.
Yes. Dato-DXd is the abbreviated name for datopotamab deruxtecan, the same investigational antibody-drug conjugate developed by AstraZeneca. Trial records use both names, including the Phase 2 urothelial cancer study NCT07129993, which refers to datopotamab deruxtecan in its title.