Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Patritumab Deruxtecan (Fixed dose), HER3-DXd, U31402, MK-1022
Patritumab Deruxtecan · 8 trials · 22 indications
PFS is defined as the time from first day of study intervention to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by blinded independent central review (BICR). Per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.
OS is the length of time from when the participant starts treatment until death from any cause.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be presented for Part 1.
A DLT is defined by the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, assessed by investigator as drug-related: Grade (gr) 3 or 4 nonhematologic toxicity (with exceptions); gr 3 or gr 4 laboratory values (with exceptions); gr 3 or 4 febrile neutropenia; prolonged delay (\>2 weeks) in initiating Cycle 2 (cycle length = 3 weeks) due to intervention-related toxicity; any intervention-related toxicity that causes the participant to discontinue intervention during Cycle 1; interstitial lung disease as per investigator; any other gr ≥3 pulmonary toxicity; or gr 5 toxicity.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinued study treatment due to an AE will be presented for Part 1.
pCR (ypT0/Tis ypN0) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes after completion of neoadjuvant systemic therapy at the time of definitive surgery.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be presented for Part 2.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinued study treatment due to an AE will be presented for Part 2.
Confirmed objective response rate (ORR) is defined as the sum of the complete response (CR) rate and partial response (PR) rate based on investigator by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
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 BICR 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 based on RECIST v1.1.
Adverse event(AE): any untoward medical occurrence in a participant administered pharmaceutical product (PP) and which does not necessarily have a causal relationship with the treatment.AE can therefore be any unfavorable and unintended sign(including an abnormal laboratory finding, for example),symptom,or disease temporally associated with the use of PP, whether or not considered related to the PP.Pre-existing conditions which worsen during study are also considered as AEs.SAE:any AE that fulfilled any of following criteria:fatal,life-threatening,required inpatient hospitalisation or prolongation of existing hospitalization,resulted in persistent or significant disability/incapacity,was congenital anomaly/birth defect, medically significant or required intervention to prevent any of the other outcomes listed here. TEAEs:AEs with start or worsening date during the on-treatment period(from 1st dose date of trial intervention to 47 days after the last dose date of trial intervention).
Objective response is defined as 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.
A DLT is any of a prespecified list of adverse events (AEs) that occur during Cycle 1 (up to 21 days) if attributed to the study treatment and not attributed to any other clearly identifiable cause. The percentage of participants who experience DLTs will be reported. Each cycle is 21 days.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experience AEs will be reported.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinue study treatment due to an AE will be reported.
Blood samples will be collected at specified intervals for the determination of AUC.
Blood samples will be collected at specified intervals for the determination of AUC.
Blood samples will be collected at specified intervals for the determination of AUC.
Blood samples will be collected at specified intervals for the determination of Cmax.
Blood samples will be collected at specified intervals for the determination of Cmax.
Blood samples will be collected at specified intervals for the determination of Cmax.
Blood samples will be collected at specified intervals for the determination of Ctrough.
Blood samples will be collected at specified intervals for the determination of Ctrough.
Blood samples will be collected at specified intervals for the determination of Ctrough.
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by the investigator will be presented.
DLT will be defined as any drug-related AE observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle. The number of participants who experience a DLT will be presented.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be presented.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study treatment due to an AE will be presented.
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR)will be presented.
DLT will be defined as any drug-related adverse event observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next 21-day cycle. The number of participants in the dose-escalation phase who experience a DLT will be presented.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be presented.
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study treatment due to an AE will be presented.
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
| Arm | Type | Description |
|---|---|---|
| Patritumab Deruxtecan | EXPERIMENTAL | Participants receive patritumab deruxtecan via intravenous (IV) infusion every 3 weeks (Q3W) for approximately 13 months. |
| Treatment of Physician's Choice | ACTIVE_COMPARATOR | Participants receive treatment of physician's choice (TPC) for up to 13 months. The TPC may be any of the following options: Paclitaxel (80 mg/m\^2) on Days 1, 8, 15, and 22 of each 4-week cycle; Paclitaxel (90 mg/m\^2) on Days 1, 8, and 15 of each 4-week cycle; Nab-paclitaxel (100 mg/m\^2) on Days 1, 8, and 15 of each 4-week cycle; Capecitabine (1000 mg/m\^2) bid on Days 1 to 14 of each 3-week cycle; Pegylated liposomal doxorubicin (50 mg/m\^2) on Day 1 of each 4-week cycle; or trastuzumab deruxtecan (T-DXd) (5.4 mg/kg) Q3W. |
| Part 1, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin | EXPERIMENTAL | In Part 1, participants receive neoadjuvant pembrolizumab 200 mg via intravenous (IV) infusion every 3 weeks (Q3W) plus patritumab deruxtecan via IV infusion Q3W for 12 weeks, followed by pembrolizumab 200 mg via IV infusion Q3W plus paclitaxel 80 mg/m\^2 via IV infusion every week (QW) and carboplatin AUC1.5 mg/ml/min via IV infusion QW for 12 weeks. At 3 to 6 weeks after last dose of neoadjuvant treatment, participants will undergo surgery for their breast cancer. |
| Part 2, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin | EXPERIMENTAL | In Part 2, participants receive neoadjuvant pembrolizumab 200 mg IV infusion every Q3W plus patritumab deruxtecan (dose to be determined in part 1) IV infusion Q3W for 12 weeks, followed by pembrolizumab 200 mg IV infusion Q3W plus paclitaxel 80 mg/m\^2 IV infusion QW and carboplatin AUC1.5 mg/ml/min IV infusion QW for 12 weeks. At 3-6 weeks after last dose of neoadjuvant treatment, participants undergo surgery for breast cancer. After surgery, participants receive adjuvant pembrolizumab 400 mg IV every 6 weeks (Q6W) for \~30 weeks. Additional adjuvant treatment of physician's choice (TPC) may be given to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline BRCA mutation \[gBRCAm\] only), capecitabine 1000-1250 mg/m\^2 oral BID days 1-14 and 22-35 Q6W for 4 six-week cycles or doxorubicin 60mg/m\^2 (or epirubicin 90 mg/m\^2) IV Q3W or every 2 weeks (Q2W) and cyclophosphamide 600 mg/m\^2 IV Q3W or Q2W for 4 doses. |
| Part 2, B: Pembrolizumab + paclitaxel + carboplatin → Pembrolizumab + patritumab deruxtecan | EXPERIMENTAL | In Part 2, participants receive neoadjuvant pembrolizumab 200 mg IV infusion Q3W plus paclitaxel 80 mg/m\^2 IV infusion QW and carboplatin AUC1.5 mg/ml/min IV infusion QW for 12 weeks, followed by pembrolizumab 200 mg IV infusion Q3W plus patritumab deruxtecan (dose to be determined in part 1) via IV infusion Q3W for 12 weeks. At 3 to 6 weeks after last dose of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will receive adjuvant pembrolizumab 400 mg IV infusion Q6W for \~30 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options include olaparib 300 mg oral BID for 1 year (participants with gBRCAm only), capecitabine 1000-1250 mg/m\^2 oral BID days 1-14 and 22-35 Q6W for 4 six-week cycles or doxorubicin 60mg/m\^2 (or epirubicin 90 mg/m\^2) IV infusion Q3W or Q2W and cyclophosphamide 600 mg/m\^2 IV infusion Q3W or Q2W for 4 doses. |
| Part 2, C: Pembro + paclitaxel + carboplatin→ Pembro + doxorubicin (or epirubicin) +cyclophosphamide | ACTIVE_COMPARATOR | In Part 2, participants receive neoadjuvant pembrolizumab 200 mg IV infusion Q3W plus paclitaxel 80 mg/m\^2 IV infusion QW and carboplatin AUC1.5 mg/ml/min via IV infusion QW for 12 weeks, followed by pembrolizumab 200 mg IV infusion Q3W plus doxorubicin 60mg/m\^2 (or epirubicin 90 mg/m\^2) IV infusion Q3W and cyclophosphamide 600 mg/m\^2 IV infusion Q3W for 12 weeks. At 3 to 6 weeks after last dose of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will receive adjuvant pembrolizumab 400 mg IV infusion Q6W for approximately 30 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options include olaparib 300 mg oral BID for 1 year (participants with gBRCAm only) or capecitabine 1000-1250 mg/m\^2 oral BID days 1-14 and 22-35 Q6W for 4 six-week cycles. |
| HER3-DXd Monotherapy | EXPERIMENTAL | Participants with locally advanced unresectable or metastatic cancer (melanoma, head and neck, gastric cancer, ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, prostate cancer, second-line gastric cancer, lung cancer, and breast cancer) will receive an intravenous infusion of HER3-DXd monotherapy 5.6 mg/kg every 3 weeks (Q3W). |
| Study Group 1: Patritumab deruxtecan 5.6 mg/kg | EXPERIMENTAL | Study Group 1 will be participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation randomized to receive patritumab deruxtecan 5.6 mg/kg IV every 3 weeks (Q3W) |
| Study Group 2: Patritumab deruxtecan Up-Titration | EXPERIMENTAL | Study Group 2 will be participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation randomized to receive patritumab deruxtecan up-titration IV every 3 weeks (Q3W) |
| Part 1: Arm 1: Dose Regimen Determination | EXPERIMENTAL | Participants with unresectable or metastatic breast cancer (mBC) will receive T-DXd and HER3-DXd in combination regimen A until disease progression, death, unacceptable toxicity, or trial close. |
| Part 1: Arm 2: Dose Regimen Determination | EXPERIMENTAL | Participants with unresectable or mBC will receive T-DXd and HER3-DXd in combination regimen B until disease progression, death, unacceptable toxicity, or trial close. |
| Part 2: Arm 3: Dose Expansion | EXPERIMENTAL | Participants with unresectable or mBC will receive T-DXd and HER3-DXd in a combination regimen based on the available Part 1 data until disease progression, death, unacceptable toxicity, or trial close. |
| Part 2: Arm 4: Monotherapy | ACTIVE_COMPARATOR | Participants with unresectable or mBC will receive T-DXd monotherapy until disease progression, death, unacceptable toxicity, or trial close. |
| Part 1: Patritumab deruxtecan plus trastuzumab | EXPERIMENTAL | Participants receive patritumab deruxtecan intravenous (IV) infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision. |
| Part 1: Patritumab deruxtecan plus pertuzumab and trastuzumab | EXPERIMENTAL | Participants receive patritumab deruxtecan IV infusion, pertuzumab IV infusion, and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision. |
| Part 1: Patritumab deruxtecan plus trastuzumab and tucatinib | EXPERIMENTAL | Participants receive patritumab deruxtecan IV infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks), and tucatinib is administered orally twice daily for each 21-day cycle, until disease progression, intolerable toxicity, or investigator decision. |
| Part 2: Patritumab deruxtecan plus pertuzumab and trastuzumab | EXPERIMENTAL | Participants receive patritumab deruxtecan IV infusion, pertuzumab IV infusion, and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision. |
| Name | Type | Description |
|---|---|---|
| Patritumab deruxtecan | BIOLOGICAL | Administered via intravenous (IV) infusion |
| Paclitaxel | DRUG | Administered via IV infusion |
| Nab-paclitaxel | DRUG | Administered via IV infusion |
| Capecitabine | DRUG | Administered via oral tablets |
| Pegylated liposomal doxorubicin | DRUG | Administered via IV infusion |
| Trastuzumab deruxtecan | BIOLOGICAL | Administered via IV infusion |
| Rescue Medication | DRUG | Participants receive rescue medications according to each approved drug's product label. Recommended rescue medications include: 5-HT3 receptor antagonist, NK-1 receptor antagonist, and corticosteroids. |
| Pembrolizumab | BIOLOGICAL | Administered via IV infusion as neoadjuvant treatment in Part 1 and via IV infusion as neoadjuvant and adjuvant treatment in Part 2 |
| Carboplatin | DRUG | Administered via IV infusion as neoadjuvant treatment |
| Doxorubicin hydrochloride | DRUG | Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2 |
| Epirubicin hydrochloride | DRUG | Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2 |
| Cyclophosphamide | DRUG | Administered via IV infusion as neoadjuvant treatment in Arm C and an option for adjuvant treatment for participants with residual disease in Arms A and B in Part 2 |
| Olaparib | DRUG | Administered via oral tablets as an option for adjuvant treatment for participants with germline BRCA mutations and residual disease in Part 2 |
| HER3-DXd | DRUG | Intravenous infusion 5.6 mg/kg administered Q3W on Day 1 of each 21-day cycle |
| Patritumab Deruxtecan (Fixed dose) | DRUG | Patritumab deruxtecan will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle. |
| Patritumab Deruxtecan (Up-Titration) | DRUG | Patritumab deruxtecan will be dosed as an intravenous (IV) infusion administered at Cycle 1, 3.2 mg/kg; Cycle 2, 4.8 mg/kg; Cycle 3 and subsequent cycles, 6.4 mg/kg administered on Day 1 of each 21-day cycle. |
| Trastuzumab | BIOLOGICAL | Trastuzumab administered via IV infusion |
| Trastuzumab Biosimilar | BIOLOGICAL | Trastuzumab biosimilar administered via IV infusion |
| Pertuzumab | BIOLOGICAL | Pertuzumab administered via IV infusion |
| Tucatinib | BIOLOGICAL | Tucatinib administered as oral tablets |
Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has a diagnosis of hormone receptor positive (HR+)/human epidermal growth factor receptor 2 (HER2)- invasive breast carcinoma that is either locally advanced disease not amenable to resection with curat...
Patritumab Deruxtecan is an investigational antibody-drug conjugate being developed by Merck & Company, Inc. (MRK) for oncology indications. It is being studied in advanced solid tumors, breast cancer, gastrointestinal cancer, hormone receptor positive disease, malignant neoplasms, and metastatic non-small cell lung cancer. It is not yet approved and remains in clinical development.
Patritumab Deruxtecan targets ERBB3, also known as HER3. It is an antibody-drug conjugate that binds to the ERBB3 receptor and delivers a cytotoxic payload to cells expressing that target. ERBB3 is a member of the EGFR family of receptor tyrosine kinases, and the drug is classified as an inhibitor.
Patritumab Deruxtecan is being developed by Merck & Company, Inc., which trades under the ticker MRK. Merck is running the clinical development program for the drug across multiple solid tumor and breast cancer settings.
Patritumab Deruxtecan is in Phase 2 development overall, with individual trials spanning Phase 1 through Phase 3. It is investigational and has not been approved by the FDA. Three trials are currently active, with no completed trials reported and total planned enrollment of 1,553 participants.
Patritumab Deruxtecan is being studied in NCT07701941, a Phase 1 combination trial with trastuzumab deruxtecan in HR-positive, HER2-low or HER2-ultralow metastatic breast cancer; NCT07060807, a Phase 3 breast cancer study; NCT06941272, a Phase 1 pediatric solid tumor study; and NCT06797635, a Phase 2 breast cancer trial.
Yes. Patritumab Deruxtecan is also known as HER3-DXd and as Patritumab Deruxtecan (Fixed dose). These names refer to the same antibody-drug conjugate targeting ERBB3, so search results and trial listings using any of these names describe the same investigational agent.