Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as DS-8201a (DP1), Trastuzumab deruxtecan (T-DXd), Trastuzumab deruxtecan, Experimental product, T-DXd, ENHERTU®, Trastuzumab deruxtecan (DS-8201a)
DS-8201a · 33 trials · 35 indications
Overall survival (OS) is defined as the time from date of randomization until death from any cause.
PFS is defined as the time from initiation of T-DXd + pertuzumab until PD or death, whichever occurs first.
Defined as time from randomization until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause.
TTNT is defined as the time interval from the date of first dose of T-DXd to the initiation of the next anticancer treatment or death due to any cause.
Defined as time from randomization until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause.
Proportion of participants who have no evidence by Hematoxylin \& Eosin (H\&E) staining of residual invasive disease in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by central evaluation following completion of neoadjuvant therapy.
The ORR is defined as the percentage (%) of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by independent central review (ICR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
The PFS rate is the percentage of participants alive and free of disease progression at 12 months, estimated by the Kaplan-Meier method.
Defined as time from date of randomisation until the date of objective radiological disease progression according to Blinded Independent Central Review (BICR) using RECIST 1.1 or death by any cause.
PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessed by BICR was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions (TLs), taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 millimeter (mm) from nadir. Median PFS was calculated using Kaplan-Meier method and its confidence interval (CI) using Brookmeyer-Crowley method.
Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.
Progression-free survival (PFS) by BICR was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
Progression-free survival (PFS) by BICR was defined as the time from the date of randomization to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause.
pCR rate is the proportion of participants with absent invasive carcinoma in the breast and lymph nodes at time of surgery; in situ disease only is considered pCR; if off-treatment prior to surgery than considered not pCR.
Number of patients to achieve radiologic response as defined by RECIST 11 with clearnace of ctDNA
Confirmed objective response rate (ORR), defined as the number (percentage) of participants with complete response (CR) or partial response (PR), were assessed by blinded independent central review (BICR) based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.
The confirmed Objective Response Rate to Trastuzumab Deruxtecan by RECIST (Response Evaluation Criteria In Solid Tumors) defined as the cumulative rate of complete response (CR) rate and partial response (PR) rates, evaluated according to mRECIST v1.1
Confirmed ORR is the proportion of patients who have a confirmed complete response or confirmed partial response per RECIST 1.1.
compared between patients treated with T-DXd neoadjuvant monotherapy for 18 weeks (part 1, cohort 2) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled)
dDFS in patients with T-DXd neoadjuvant monotherapy (pooled experimental treatment arms of part 1, pooled cohorts 1 and 2)
in patients with T-DXd neoadjuvant therapy followed by CHT (pooled experimental treatment arms of part 2, cohort 3)
defined as ypT0is/ypN0, compared between patients treated with T-DXd neoadjuvant monotherapy (pooled experimental treatment arms of part 1, pooled cohorts 1 and 2) compared to patients of corresponding standard-of-care treatments (DOC/PAC+T+P or DOC/PAC+Carbo+T+P) (pooled standard-of-care treatment arms of part 1, pooled cohorts 1 and 2)
Confirmed ORR, defined as the percentage of participants with confirmed complete response or partial response, as assessed by independent central review(ICR) based on RECIST 1.1.
Confirmed ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, as determined by ICR per RECIST 1.1.
The best response based on the overall visit responses from each RECIST 1.1 assessment or the last evaluable assessment in the absence of RECIST 1.1 progression
Confirmed ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR), as determined by ICR per RECIST v1.1. A CR was defined as disappearance of all target lesions (TLs) and PR was defined as at least a 30% decrease in the sum of the diameters (dms) of TL, taking as reference the baseline sum of diameters as long as criteria for PD were not met. An ICR of all radiological imaging data was carried out using RECIST v1.1. All images were collected centrally. The imaging scans were reviewed by 2 independent radiologists and were adjudicated, if required.
Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed.
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.
TEAEs are defined as those Adverse Events (AEs) with start or worsening date during the on-treatment period (from the first dose date of trial intervention to 21 days after the last dose date of trial intervention).
Objective response rate (ORR) is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) as assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria In Solid Tumors v1.1.
Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0
Occurrence of AEs in Part 1 graded according to NCI CTCAE v5.0
Occurrence of SAEs in Part 1 graded according to NCI CTCAE v5.0
Occurrence of AEs in Part 2 graded according to NCI CTCAE v5.0
Occurrence of SAEs in Part 2 graded according to NCI CTCAE v5.0
Adverse events (AEs) were to be coded using MedDRA Version 20.1 and assigned severity grades based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. A treatment-emergent adverse event (TEAE) was defined as an AE that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after initiating the study drug until 47 days after last dose of study drug.
Maximum concentration (Cmax) was assessed for DS-8201a and total Anti-HER2 antibody.
Maximum concentration (Cmax) was assessed for MAAA-1181a.
Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) for DS-8201a and total anti-HER2 antibody were assessed.
Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for MAAA-1181a.
Maximum concentration (Cmax) was assessed for DS-8201a and total Anti-HER2 antibody.
Maximum concentration (Cmax) was assessed for MAAA-1181a.
Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for DS-8201a and total anti-HER2 antibody.
Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for MAAA-1181a.
The number of participants with notable electrocardiogram changes meeting predefined criteria is being reported.
Maximum serum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.
Maximum serum concentration (Cmax) of MAAA-1181 was assessed.
Area under the concentration versus-time curve from time 0 to the last quantifiable concentration (AUClast) and during the dosing interval (AUCtau) of DS-8201a and total anti-HER2 antibody were assessed.
Area under the concentration versus-time curve from time 0 to the last quantifiable concentration (AUClast) and during the dosing interval (AUCtau) were assessed.
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 | EXPERIMENTAL | Participants who will be randomized to receive a 6.4 mg/kg intravenous (IV) dose of trastuzumab deruxtecan once every 3 weeks on Day 1 of each 21-day cycle. |
| Ramucirumab + paclitaxel | ACTIVE_COMPARATOR | Participants who will be randomized to receive a 8 mg/kg IV dose of ramucirumab on Days 1 and 15 in combination with 80 mg/m\^2 IV dose of paclitaxel on Days 1, 8, and 15 of a 28-day cycle. |
| T-DXd | EXPERIMENTAL | Adult participants with previously untreated advanced or metastatic HER2+/HR+ breast cancer who will receive T-DXd intravenously every 3 weeks (IV Q3W) in 3 treatment phases: Upfront treatment phase: T-DXd + pertuzumab IV Q3W Maintenance treatment phase: Trastuzumab + palbociclib + endocrine therapy + pertuzumab IV Q3W T-DXD retreatment phase: T-DXd monotherapy IV Q3W |
| Arm A: T-DXd + Rilvegostomig | EXPERIMENTAL | T-DXd IV Q3W plus rilvegostomig IV Q3W. Treatment will continue until objective disease progression according to RECIST v1.1 as assessed by the Investigator and confirmed by BICR or until other discontinuation criteria is met, whichever occurs first. |
| Arm B: T-DXd + Pembrolizumab | EXPERIMENTAL | T-DXd IV Q3W plus pembrolizumab IV Q3W. Treatment will continue until objective disease progression according to RECIST v1.1 as assessed by the Investigator and confirmed by BICR or until other discontinuation criteria is met, whichever occurs first. |
| Arm C: Carboplatin + Paclitaxel + Pembrolizumab | ACTIVE_COMPARATOR | Carboplatin, paclitaxel and pembrolizumab administered Q3W for 6 cycles, followed by maintenance with pembrolizumab IV Q6W for 14 cycles. Treatment with pembrolizumab will continue for up to 20 total cycles (approximately 24 months, accounting for combination and maintenance phases) or until other discontinuation criteria is met, whichever occurs first. At the discretion of the investigator, participants may continue to receive carboplatin, paclitaxel and pembrolizumab Q3W for up to 10 cycles. Docetaxel can be used as an alternative to paclitaxel for participants who had a hypersensitivity reaction to paclitaxel with a failed rechallenge (or not amenable to rechallenge), according to the investigator's clinical judgment. |
| Cohort 1: HR-negative, HER2-low | EXPERIMENTAL | Participants with HR-negative HER2-low unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd. |
| Cohort 2: HR-negative, HER2 IHC 0 | EXPERIMENTAL | Participants with HR-negative HER2 IHC 0 unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd. |
| Cohort 3: HR-positive, HER2-low | EXPERIMENTAL | Participants with HR-positive HER2-low unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd. Participants must also have recurrent disease \<2 years from the initiation of adjuvant ET or have disease progression on CDK4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a CDK4/6 inhibitor or have disease progression within the first 12 months of CDK4/6 in the first line metastatic setting. |
| Cohort 4: HR-positive, HER2 IHC 0 | EXPERIMENTAL | Participants with HR-positive HER2 IHC 0 unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd. |
| Arm 1 | EXPERIMENTAL | Trastuzumab Deruxtecan (T-DXd) |
| Arm 2 | ACTIVE_COMPARATOR | Standard of Care Treatment (platinum, pemetrexed and pembrolizumab) |
| Arm A | EXPERIMENTAL | Trastuzumab deruxtecan |
| Arm B | EXPERIMENTAL | T-DXd, followed by THP |
| Arm C | ACTIVE_COMPARATOR | doxorubicin and cyclophosphamide, followed by THP |
| 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. |
| Standard of Care | ACTIVE_COMPARATOR | Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm |
| Physician's Choice | ACTIVE_COMPARATOR | HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to Physician's choice from the following options: * Capecitabine * Eribulin * Gemcitabine * Paclitaxel * Nab-paclitaxel |
| Ado-trastuzumab emtansine (T-DM1) | ACTIVE_COMPARATOR | Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label. |
| Trastuzumab deruxtecan (DS-8201a) | EXPERIMENTAL | HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), randomized to treatment with DS-8201a |
| Trastuzumab+capecitabine | ACTIVE_COMPARATOR | HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), randomized to investigator's choice treatment with Trastuzumab/capecitabine |
| Lapatinib+capecitabine | ACTIVE_COMPARATOR | HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), randomized to investigator's choice treatment with Lapatinib/capecitabine |
| HER2 Positive | EXPERIMENTAL | Participants will be enrolled into one of two cohorts: HER2 positive IBC (cohort 1) and HER2 low IBC (cohort 2). * HER2-positive determined locally by the current ASCO/CAP guidelines * Participants will receive trastuzumab deruxtecan plus durvalumab for eight cycles prior to surgery. (Cycle Length is 21 days) * After surgery, Participants will receive therapy per physician's choice and to reflect current standard of care. |
| HER2-Low | EXPERIMENTAL | Participants will be enrolled into one of two cohorts: HER2 positive IBC (cohort 1) and HER2 low IBC (cohort 2) * HER2-low tumor expression (IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested) * Participants will receive trastuzumab deruxtecan plus durvalumab for eight cycles prior to surgery (Cycle Length is 21 days) * After surgery, Participants will receive therapy per physician's choice and to reflect current standard of care. |
| Trastuzumab-deruxtecan | EXPERIMENTAL | 5.4mg/kg on a three weekly (21 day) basis, with the goal of 16 cycles leading to a treatment period of year, including local treatment. The first 8 cycles of T-DXd are administered neo-adjuvant, and 8 cycles adjuvant, after completion of local treatment. |
| T-DXd 5.4 mg/kg Q3W | EXPERIMENTAL | Participants will be randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W). |
| T-DXd 6.4 mg/kg Q3W | EXPERIMENTAL | Participants will be randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W). |
| Part 1 | EXPERIMENTAL | HER2 IHC 3+ solid tumors (excluding breast and gastric cancer) |
| Part 2 Cohort A | EXPERIMENTAL | HER2 IHC 2+ solid tumors (excluding breast and gastric cancer) |
| Part 2 Cohort B | EXPERIMENTAL | HER2 IHC 1+ gynecologic cancers |
| Part 3 | EXPERIMENTAL | HER2 IHC 3+ or 2+ cervical cancer |
| T-DXd 12 weeks: HER2+ and low-intermediate risk for recurrence | EXPERIMENTAL | 12 weeks T-DXd i.v. in neoadjuvant treatment; pCR dependent T-DXd for 1 year in total in postneoadjuvant treatment |
| T-DXd 18 weeks: HER2+ and intermediate-high risk for recurrence | EXPERIMENTAL | 18 weeks T-DXd i.v. in neoadjuvant treatment; pCR dependent T-DXd for 1 year in total in postneoadjuvant treatment |
| Control SoC CTx 12 weeks: HER2+ and low-intermediate risk for recurrence | OTHER | Standard-of-Care-Treatment: 12 weeks PAC+T+P (standard-of-care) in neoadjuvant treatment; pCR dependent SOC chemotherapy +T+/-P or SOC T+/-P for 1 year in total in postneoadjuvant treatment |
| Control SoC CTx 18 weeks: HER2+ and intermediate-high risk for recurrence | OTHER | Standard-of-Care-Treatment: 18 weeks PAC/DOC+Carbo+T+P (standard-of-care) in neoadjuvant treatment; pCR dependent SOC chemotherapy +T+/-P or SOC T+/-P for 1 year in total in postneoadjuvant treatment |
| T-DXd 12 weeks + SoC CTx 6 weeks | EXPERIMENTAL | 12 weeks T-DXd i.v. follwed by 6 weeks SoC chemotherapy in neoadjuvant treatment; pCR dependent postneoadjuvant treatment: * non-pCR: 14 cycles of T-DXd is strongly recommended or SoC treatment, i.e., chemotherapy and anti-HER2-treatment, including T-DM1 at investigator´s decision * pCR: SoC treatment, e.g., T +/- P or T-DM1 (at investigator´s decision) |
| T-DXd 12 weeks + SoC CTx 12 weeks | EXPERIMENTAL | 12 weeks T-DXd i.v. follwed by 12 weeks SoC chemotherapy in neoadjuvant treatment; pCR dependent postneoadjuvant treatment: * non-pCR: 14 cycles of T-DXd is strongly recommended or SoC treatment, i.e., chemotherapy and anti-HER2-treatment, including T-DM1 at investigator´s decision * pCR: SoC treatment, e.g., T +/- P or T-DM1 (at investigator´s decision) Therapy for patients with non-pCR who received neoadjuvant T-DXd (12 weeks) + 12 weeks (4 cycles) of SoC chemotherapy will exceed total therapy over one year. Here, approximately 66 weeks are considered as maximum therapy (individual variations may apply) |
| SoC CTx 18 weeks | OTHER | Standard-of-Care-Treatment: 18 weeks PAC/DOC+Carbo+T+P (standard-of-care) in neoadjuvant treatment; pCR dependent SOC chemotherapy +T+/-P or SOC T+/-P for 1 year in total in postneoadjuvant treatment * non-pCR (in particular ypT \>1b (5 mm) or ypN+: 14 cycles with T-DXd recommended * pCR: SoC treatment, e.g., T +/- P or T-DM1 (at investigator´s decision) Therapy for patients with non-pCR who received neoadjuvant SoC chemotherapy will exceed total therapy over one year. Here, approximately 60 weeks are considered as maximum therapy (individual variations may apply). |
| T-DXd arm | EXPERIMENTAL | Participants will receive T-DXd as an IV infusion Q3W, on Day 1 of each 3-week cycle. |
| Part 1 Cohort 1 | EXPERIMENTAL | Biliary tract cancer |
| Part 1 Cohort 2 | EXPERIMENTAL | Bladder cancer |
| Part 1 Cohort 3 | EXPERIMENTAL | Cervical cancer |
| Part 1 Cohort 4 | EXPERIMENTAL | Endometrial cancer |
| Part 1 Cohort 5 | EXPERIMENTAL | Ovarian cancer |
| Part 1 Cohort 6 | EXPERIMENTAL | Pancreatic cancer |
| Part 1 Cohort 7 | EXPERIMENTAL | Rare tumors |
| Part 2 Cohort C | EXPERIMENTAL | HER2 IHC 2+ or 1+ endometrial cancer |
| Part 2 Cohort D | EXPERIMENTAL | HER2 IHC 2+ or 1+ ovarian cancer |
| Part 2 Cohort E | EXPERIMENTAL | HER2 IHC 2+ or 1+ cervical cancer |
| 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 | Participants will receive Trastuzumab Deruxtecan subcutaneously at escalating doses. The recommended dose for expansion (RDE) will be calculated using data collected from this population. |
| Part 2 (Dose Expansion) | EXPERIMENTAL | Participants will receive Trastuzumab Deruxtecan subcutaneously at the recommended dose for expansion (RDE) |
| Dose Escalation: DS-1103a + T-DXd | EXPERIMENTAL | Participants with HER2-expressing or HER2-mutated advanced metastatic solid tumors who will receive an escalating intravenous (IV) infusion of DS-1103a (starting dose of 100 mg) every 3 weeks (Q3W) starting on Cycle 1 Day 1. Starting on Cycle 2 Day 1 and on Day 1 of each subsequent cycle, participants will also receive T-DXd IV Q3W. |
| Dose Expansion (Cohort 1): DS-1103a + T-DXd | EXPERIMENTAL | Participants with a specific HER2-altered advanced solid tumor type who will receive an IV infusion of DS-1103a at the recommended dose for expansion (RDE) in combination with T-DXd IV Q3W starting on Cycle 1 Day 1. |
| Dose Expansion (Cohort 2): DS-1103a + T-DXd | EXPERIMENTAL | Participants with a specific HER2-altered advanced solid tumor type who will receive an IV infusion of DS-1103a at the recommended dose for expansion (RDE) in combination with T-DXd IV Q3W starting on Cycle 1 Day 1. |
| Arm 1A: T-DXd, Durvalumab and Cisplatin | EXPERIMENTAL | T-DXd, Durvalumab and Cisplatin |
| Arm 1B: T-DXd, Durvalumab and Carboplatin | EXPERIMENTAL | T-DXd, Durvalumab and Carboplatin |
| Arm 1C: T-DXd, Durvalumab and Pemetrexed | EXPERIMENTAL | T-DXd, Durvalumab and Pemetrexed (Arm not initiated) |
| Arm 1D: T-DXd | EXPERIMENTAL | T-DXd |
| Arm 3A: T-DXd and Volrustomig | EXPERIMENTAL | Drug: T-DXd and Volrustomig T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Volrustomig Volrustomig: administered as an IV infusion Other Name: Volrustomig |
| Arm 3B: T-DXd, Volrustomig and Carboplatin | EXPERIMENTAL | Drug: T-DXd, Volrustomig and Carboplatin T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Volrustomig Volrustomig: administered as an IV infusion Other Name: Volrustomig Drug: Carboplatin Carboplatin: administered as an IV infusion |
| Arm 4A: T-DXd and Rilvegostomig | EXPERIMENTAL | T-DXd and Rilvegostomig Drug: T-DXd, Rilvegostomig T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Rilvegostomig Rilvegostomig: administered as an IV infusion Other Name: Rilvegostomig, AZD2936 |
| Arm 4B T-DXd and Rilvegostomig with Carboplatin | EXPERIMENTAL | Drug: T-DXd, Rilvegostomig and Carboplatin T-DXd: administered as an IV infusion Other Name: DS-8201a, Trastuzumab deruxtecan Biological/Vaccine: Rilvegostomig Rilvegostomig: administered as an IV infusion Other Name: Rilvegostomig, AZD2936 Drug: Carboplatin Carboplatin: administered as an IV infusion |
| Arm 5A: T-DXd and Volrustomig | EXPERIMENTAL | Drug: T-DXd and volrustomig T-DXd: administered as an IV infusion Other Name: DS-8201a, trastuzumab deruxtecan Biological/Vaccine: Volrustomig Volrustomig: administered as an IV infusion (priming dose in first cycle, fixed dose in subsequent cycles) Other Name: volrustomig |
| Arm 5B: T-DXd and Volrustomig | EXPERIMENTAL | Drug: T-DXd and volrustomig T-DXd: administered as an IV infusion Other Name: DS-8201a, trastuzumab deruxtecan Biological/Vaccine: Volrustomig Volrustomig: administered as an IV infusion (fixed dose from first cycle onward) Other Name: volrustomig |
| Module 1- T-DXd and Durvalumab | EXPERIMENTAL | T-DXd and Durvalumab |
| Module 2- T-DXd and Pertuzumab | EXPERIMENTAL | T-DXd and Pertuzumab |
| Module 3- T-DXd and Paclitaxel | EXPERIMENTAL | T-DXd and Paclitaxel (Arm not initiated in Part 2) |
| Module 4- T-DXd and Durvalumab and Paclitaxel | EXPERIMENTAL | T-DXd and Durvalumab and Paclitaxel (Arm not initiated in Part 1 and Part 2) |
| Module 0- T-DXd | EXPERIMENTAL | T-DXd |
| Module 5 - T-DXd and Tucatanib | EXPERIMENTAL | T-DXd and tucatinib (Arm not initiated in Part 2) |
| Module 6 - T-DXd and Tucatinib | EXPERIMENTAL | T-DXd and tucatinib in patients with active brain metastases (Part 2 Only) (Arm not initiated) |
| Module 7 - T-DXd | EXPERIMENTAL | T-DXd monotherapy in patients with active brain metastases (Part 2 Only) |
| Module 1: T-DXd + capecitabine | EXPERIMENTAL | T-DXd: 5.4 mg/kg Q3W, intravenous use Capecitabine: 1000mg/m2 BID, days 1-14 Q3W, oral use |
| Module 2: T-DXd + durvalumab + paclitaxel | EXPERIMENTAL | T-DXd: 5.4 mg/kg Q3W, intravenous use Durvalumab: 1120 mg Q3W, intravenous use Paclitaxel: 80 mg/m2 QW in 3-week cycles, intravenous use |
| Module 3: T-DXd + capivasertib | EXPERIMENTAL | T-DXd: 5.4 mg/kg Q3W, intravenous use Capivasertib: 400 mg BID, oral use |
| Module 4: T-DXd + anastrozole | EXPERIMENTAL | T-DXd: 5.4 mg/kg Q3W, intravenous use Anastrozole: 1 mg daily, oral |
| Module 5: T-DXd + fulvestrant | EXPERIMENTAL | T-DXd: 5.4 mg/kg Q3W, intravenous use Fulvestrant: 500 mg Q4W, intramuscular use |
| DS-8201a | EXPERIMENTAL | DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks (Q3W) |
| Cohort 1: DS-8201a + Ritonavir | EXPERIMENTAL | DS-8201a will be administered as an intravenous (IV) solution once every 3 weeks (Q3W) + Ritonavir twice daily (BID) on Day 17 of Cycle 2 until Day 21 of Cycle 3 |
| Cohort 2: DS-8201a + Itraconazole | EXPERIMENTAL | DS-8201a will be administered as an intravenous (IV) solution once every 3 weeks (Q3W) + Itraconazole BID on Day 17 of Cycle 2 followed by 200 mg daily (QD) until Day 21 of Cycle 3 |
| All Participants | EXPERIMENTAL | All participants will receive DS-8201a by intravenous infusion |
| 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 |
|---|---|---|
| Trastuzumab deruxtecan | DRUG | 6.4 mg/kg IV infusion every 3 weeks on Day 1 of each 21-day cycle |
| Ramucirumab | DRUG | 8 mg/kg IV infusion on Days 1 and 15 of a 28-day cycle |
| Paclitaxel | DRUG | 80 mg/m\^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle |
| Trastuzumab | DRUG | Maintenance treatment: One IV infusion Q3W 6 mg/kg on Day 1 of each 21-day cycle |
| Pertuzumab | DRUG | Upfront treatment: One IV infusion Q3W loading dose of 840 mg, then 420 mg Q3W thereafter on Day 1 of each 21-day cycle Maintenance treatment: One IV infusion Q3W 420 mg on Day 1 of each 21-day cycle |
| Endocrine Therapy | DRUG | Aromatase inhibitors or fulvestrant administered as approved product label |
| Palbociclib | DRUG | Maintenance treatment: Daily (3 out of 4 weeks, Q4W) oral 125 mg |
| Rilvegostomig | DRUG | Experimental therapy by intravenous infusion |
| Pembrolizumab | DRUG | Immunotherapy by intravenous infusion |
| Carboplatin | DRUG | Standard of Care (SoC) chemotherapy by intravenous infusion |
| Docetaxel | DRUG | Standard of Care (SoC) chemotherapy by intravenous infusion |
| Cisplatin | DRUG | Investigator's choice of platinum chemotherapy (cisplatin) administered by intravenous infusion |
| Pemetrexed | DRUG | Pemetrexed administered by intravenous infusion |
| Doxorubicin | DRUG | administered by intravenous infusion |
| cyclophosphamide | DRUG | administered by intravenous infusion |
| Placebo | DRUG | Administered by intravenous infusion |
| Taxane | DRUG | Investigator's choice of docetaxel or paclitaxel administered by intravenous infusion |
| 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 |
| Capecitabine | DRUG | Investigator's choice standard of care single agent chemotherapy; capecitabine tablets will be given orally. |
| Nab-Paclitaxel | DRUG | Investigator's choice standard of care single agent chemotherapy; nab-paclitaxel by intravenous infusion |
| Trastuzumab deruxtecan (DS-8201a) | DRUG | DS-8201a is a lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered intravenously |
| Eribulin | DRUG | Administered according to label, as one option for Physician's Choice (determined before randomization) |
| Gemcitabine | DRUG | Administered according to label, as one option for Physician's Choice (determined before randomization) |
| Trastuzumab deruxtecan (T-DXd) | DRUG | T-DXd is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered intravenously. |
| Ado-trastuzumab emtansine (T-DM1) | DRUG | The treatment will be in accordance with the approved label. |
| Lapatinib | DRUG | Investigator's choice Standard of Care when combined with capecitabine |
| Durvalumab | DRUG | via IV, protocol determined dosage once per cycle up to eight cycles. Each cycle will last for 21 days (three weeks). |
| DS-8201a 5.4 mg/kg Q3W | DRUG | DS-8201a for injection will be administered intravenously (IV) at a dose of 5.4 mg/kg every 3 weeks (Q3W) |
| DS-8201a 6.4 mg/kg Q3W | DRUG | DS-8201a for injection will be administered intravenously (IV) at a dose of 6.4 mg/kg every 3 weeks (Q3W) |
| Bevacizumab | DRUG | Bevacizumab by intravenous infusion |
| Standard-of-Care | DRUG | Chemotherapy+T+P |
| DS-1103a | DRUG | One IV infusion Q3W on Day 1 of each 21-day cycle |
| T-DXd | DRUG | One IV infusion Q3W on Day 1 of each 21-day cycle |
| Volrustomig | DRUG | Volrustomig: administered as an IV infusion |
| Tucatinib | DRUG | Tucatinib administered orally (tablet) twice daily |
| Capivasertib | DRUG | Capivasertib: administered orally |
| Anastrozole | DRUG | Anastrozole: administered orally |
| Fulvestrant | DRUG | Fulvestrant: administered as an IM injection |
| Ritonavir | DRUG | Ritonavir is a OATP1B inhibitor; an antiretroviral tablet for oral administration |
| Itraconazole | DRUG | Itraconazole is a CYP3A inhibitor; an antifungal tablet for oral administration |
| 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. |
Inclusion Criteria: * Adults (according to local regulation) and able to provide informed consent for study participation. * Pathologically documented gastric and GEJ adenocarcinoma that has been previously treated in the metastatic setting (unresectable, locally advanced, or metastatic disease). *...
DS-8201a is an antibody-drug conjugate (ADC) being developed for HER2-expressing cancers. It is being studied in breast cancer, gastric adenocarcinoma, advanced colorectal cancer, and other advanced solid tumors. AstraZeneca PLC (ticker AZN) is the developer. It is an investigational agent in clinical development.
DS-8201a targets HER2, the human epidermal growth factor receptor 2. As an antibody-drug conjugate, it binds HER2-expressing tumor cells and delivers a cytotoxic payload. Its clinical program is biomarker-selected, enrolling patients whose tumors overexpress or express HER2, including breast, gastric, and colorectal cancers.
DS-8201a is developed by AstraZeneca PLC, which trades under the ticker AZN. The company is running the clinical program across HER2-positive breast cancer, HER2-overexpressing colorectal cancer, gastric adenocarcinoma, and advanced solid tumors.
DS-8201a is in clinical development and is investigational. Its trial program spans Phase 1 through Phase 3, including a Phase 1 study in advanced solid tumors, Phase 2 studies in colorectal cancer, and the Phase 3 DESTINY-Breast05 trial in high-risk HER2-positive breast cancer.
DS-8201a has been studied in NCT04744831, a completed Phase 2 trial in HER2-overexpressing advanced or metastatic colorectal cancer; NCT03384940 (DESTINY-CRC01), a completed Phase 2 trial in HER2-expressing colorectal cancer; NCT03383692, a completed Phase 1 trial in advanced solid tumors; and NCT04622319 (DESTINY-Breast05), an active Phase 3 breast cancer trial.
Yes. DS-8201a is also known as trastuzumab deruxtecan, and it has been referenced as DS-8201a (DP1) and by dosing descriptions such as DS-8201a 5.4 mg/kg Q3W. The names DS-8201a and trastuzumab deruxtecan refer to the same HER2-targeted antibody-drug conjugate developed by AstraZeneca.