Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
DS-8201a · 3 trials · 4 indications
Best objective response was reported based on independent central review. As per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.
Objective response rate (defined as CR+PR) was reported based on independent central review. As per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.
Objective response rate (ORR) by independent central review was defined as the proportion of participants who achieve either complete response \[CR\] or partial response \[PR\] per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
| Arm | Type | Description |
|---|---|---|
| Trastuzumab deruxtecan (T-DXd) | EXPERIMENTAL | Participants who will be randomized to receive trastuzumab deruxtecan (T-DXd) at a starting dose of 5.4 mg/kg. |
| Trastuzumab ematansine (T-DM1) | ACTIVE_COMPARATOR | Participants who will be randomized to receive trastuzumab ematansine (T-DM1) at a starting dose of 3.6 mg/kg. |
| DS-8201a Cohort A | EXPERIMENTAL | Cohort A is comprised of participants with HER2-positive (IHC 3+ or IHC 2+/ISH +) who will receive DS-8201a once every 3 weeks |
| DS-8201a Cohort B | EXPERIMENTAL | Cohort B is comprised of participants with HER2 IHC 2+/ISH - who will receive DS-8201a once every 3 weeks |
| DS-8201a Cohort C | EXPERIMENTAL | Cohort C is comprised of participants with HER2 IHC 1+ who will receive DS-8201a once every 3 weeks |
| Part 1 Dose escalation | EXPERIMENTAL | Part 1 is a dose escalation to identify the Maximum Tolerated dose (MTD) or the recommended phase 2 dose of DS-8201a guided by the modified continuous reassessment method using a Bayesian logistic regression model following escalation with overdose control principal. |
| Part 2 Dose expansion | EXPERIMENTAL | Part 2 is a dose expansion to examine the safety and efficacy of DS-8201a and it is consist of multiple cohorts: in subjects with trastuzumab emtansine (T-DM1)-treated HER2 overexpressing breast cancer (Part 2a); trastuzumab-treated HER2 overexpressing gastric or gastroesophageal junction adenocarcinoma (Part 2b); HER2 low expressing breast cancer (Part 2c), HER2 expressing other solid malignant tumor (Part 2d); HER2 expressing breast cancer (Japan only; Part 2e) |
| Name | Type | Description |
|---|---|---|
| DS-8201a | DRUG | Administered initially as an intravenous (IV) infusion at a dose of 5.4 mg/kg on Day 1 of each 21-day cycle |
| T-DM1 | DRUG | Administered initially as an intravenous (IV) infusion at a dose of 3.6 mg/kg on Day 1 of each 21-day cycle |
| DS-8201a (DP1) | DRUG | DS-8201a to be administered via intravenous (IV) dose. DS-8201a (DP1) was used for the Dose Escalation phase and for Dose expansion Parts 2a, 2b, 2c, and 2d. |
| DS-8201a (DP2) | DRUG | DS-8201a is to be administered via intravenous (IV) dose. DS-8201a (DP2) was used only used for Dose Expansion Part 2e. |
| DS-8201a (DP) | DRUG | DS-8201a (DP) is to be administered via intravenous (IV) dose. |
Key Inclusion Criteria: * Adults ≥18 years old (local regulatory requirements will apply if the legal age of consent for study participation is \>18 years old). * Pathologically documented HER2-positive breast cancer (BC): * HER2-positive expression defined as an immunohistochemistry (IHC) score...
DS-8201a is an investigational oncology drug being studied for colorectal neoplasms, advanced colorectal cancer, advanced solid tumors, and HER2-positive primary breast cancer. It is a small molecule in clinical development for these cancer indications.
DS-8201a is being developed by AstraZeneca PLC, which trades under the ticker AZN. The company is conducting clinical trials to evaluate the drug's safety and efficacy in various cancer types.
DS-8201a is in Phase 1 clinical development. It is an investigational drug, meaning it has not been approved by regulatory authorities and is still undergoing clinical trials to assess its safety and effectiveness.
DS-8201a has been studied in several clinical trials, including NCT02564900 for advanced solid tumors, NCT03384940 for HER2-expressing colorectal cancer, NCT04622319 for HER2-positive breast cancer, and NCT04744831 for advanced colorectal cancer.
DS-8201a is also known as trastuzumab deruxtecan (T-DXd). Clinical trials such as NCT04622319 and NCT04744831 refer to the drug by this alternative name, confirming that DS-8201a and trastuzumab deruxtecan are the same compound.
DS-8201a clinical trials have enrolled a total of 1,600 participants across multiple studies. The largest trial, NCT04622319, has an enrollment of 1,600 participants, while other trials have smaller cohorts ranging from 86 to 292 participants.