Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Dato-DXd · 9 trials · 5 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 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 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.
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.
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.
| 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. |
| 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. |
| 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. |
| 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 |
| 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). |
| 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. |
| Osimertinib | DRUG | Osimertinib will be administered orally. |
| Pemetrexed | DRUG | Pemetrexed will be administered as IV infusion. |
| Carboplatin | DRUG | Carboplatin will be administered as IV infusion. |
| Cisplatin | DRUG | Cisplatin will be administered as IV infusion. |
| 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 |
| Vinorelbine | DRUG | IV Infusion. Active comparator |
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...
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Dato-DXd is an investigational oncology drug being studied for urothelial cancer, metastatic non-small cell lung cancer, high-risk muscle invasive urothelial carcinoma, and breast cancer. It is currently in Phase 3 clinical development for these indications.
Dato-DXd is an antibody-drug conjugate that targets the TROP2 protein, which is expressed on the surface of many solid tumor cells. By binding to TROP2, it delivers a cytotoxic payload directly to cancer cells.
Dato-DXd is being developed by AstraZeneca PLC, a biopharmaceutical company listed on the NASDAQ under the ticker symbol AZN. The company is conducting multiple Phase 3 trials for this drug candidate.
Dato-DXd is in Phase 3 clinical development. It is an investigational drug and has not yet been approved by regulatory authorities. Multiple Phase 3 trials are actively enrolling or have completed enrollment.
Dato-DXd is being evaluated in several Phase 3 trials, including NCT05104866 for HR-positive, HER2-negative breast cancer, NCT05629585 for triple-negative breast cancer, and NCT06112379 for early-stage breast cancer. A Phase 2 trial, NCT07129993, is studying it in urothelial carcinoma.
Yes, Dato-DXd is the short name for datopotamab deruxtecan. The drug is referred to by both names in clinical trial documentation and scientific literature.