DESTINY Clinical Trials
A series of international trials investigating trastuzumab deruxtecan (T-DXd)* as a potential
treatment option for eligible patients with certain cancers, including breast, gastric, lung, and
additional cancer types. Select a cancer type to learn more about current clinical trials.
Studies for patients whose primary cancer site originated in the breast.
Select a clinical trial below to learn more.
Official Title: A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in Participants With High-Risk HER2-Positive Primary Breast Cancer Who Have Residual Invasive Disease in Breast or Axillary Lymph Nodes Following Neoadjuvant Therapy (DESTINY-Breast05)
Primary Outcome Measures:
- Invasive Disease-free Survival (IDFS) in Participants Who Were Administered Trastuzumab Deruxtecan (T-DXd) Compared With Trastuzumab Emtansine (T-DM1) Treatment [ Time Frame: Randomization to date of invasive local, axillary or distant recurrence, invasive contralateral breast cancer or death from any cause (whichever occurs first), up to approximately 81 months postdose ]
Learn more about DESTINY-Breast05 and get questions you can ask your doctor.
- 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 of 3+ and/or positive by in situ hybridization (ISH) confirmed prior to study randomization
- Histologically confirmed invasive breast carcinoma
- Clinical stage at disease presentation: T1-4, N0-3, M0; patients presenting with T1N0 tumors are not eligible
-
Pathologic evidence of residual invasive carcinoma in the breast and/or axillary lymph nodes following completion of neoadjuvant therapy meeting one of the following high-risk criteria:
- Inoperable breast cancer at presentation (prior to neoadjuvant therapy), defined as clinical stages T4, N0-3, M0 or T1-3, N2-3, M0
- Operable at presentation, defined as clinical stages T1-3, N0-1, M0, with axillary node positive disease (ypN1-3) following neoadjuvant therapy
-
Completion of neoadjuvant systemic chemotherapy, including taxane and HER2-directed treatment prior to surgery
- Systemic therapy must consist of at least 6 cycles of chemotherapy with a total duration of at least 16 weeks, including at least 9 weeks of trastuzumab (± pertuzumab) and at least 9 weeks of taxane based chemotherapy. Patients may have received an anthracycline as part of neoadjuvant therapy in addition to taxane chemotherapy.
- Adequate excision as confirmed per medical records: surgical removal of all clinically evident disease in the breast and lymph nodes.
- An interval of no more than 12 weeks between the date of last surgery and the date of randomization.
- Known hormone receptor (HR) status, per local laboratory assessment, as defined by ASCO-CAP guidelines (≥1%): HR positive status defined by either positive estrogen receptor (ER) and/or positive progesterone receptor (PR) status. HR-negative status defined by both known negative ER and known negative PR.
- Left ventricular ejection fraction (LVEF) ≥50% within 28 days prior to randomization.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at Screening.
- Has adequate organ function within 14 days before randomization.
- Stage IV (metastatic) BC
- History of any prior (ipsi- or contralateral) breast cancer except lobular carcinoma in situ (LCIS)
- Evidence of clinically evident gross residual or recurrent disease following neoadjuvant therapy and surgery
- Prior treatment with T-DXd, T-DM1 or other anti-HER2 antibody-drug conjugate (ADC)
-
History of exposure to the following cumulative doses of anthracyclines:
- Doxorubicin > 240 mg/m^2
- Epirubicin or Liposomal Doxorubicin-Hydrochloride > 480 mg/m^2
- For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m^2
- History of other malignancy within the last 5 years except for appropriately treated CIS of the cervix, nonmelanoma skin carcinoma, Stage I melanoma skin carcinoma, Stage I uterine cancer, or other appropriately treated non-breast malignancies
- History of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids and/or has ILD/pneumonitis noted on computed tomography (CT) scan of the chest at Screening (asymptomatic interstitial changes confined to recent radiation therapy fields are not excluded)
- Known pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within three months prior to randomization, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease).
- Any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (eg, Rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior lobectomy or pneumonectomy
- Medical history of myocardial infarction (MI) within 6 months before randomization, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), troponin levels consistent with MI as defined according to the manufacturer 28 days prior to randomization
https://clinicaltrials.gov/ct2/show/NCT04622319.
Official Title: A Phase 3, Randomized, Multi-center, Open-label Study of Trastuzumab Deruxtecan (T-DXd) Versus Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Breast Cancer Patients Whose Disease Has Progressed on Endocrine Therapy in the Metastatic Setting (DESTINY-Breast06)
Primary Outcome Measures:
- Progression Free Survival (PFS) - in HR+, HER2-low population [ Time Frame: Until progression or death, assessed up to approximately 60 months ]
- Patients must be ≥18 years of age
-
Pathologically documented breast cancer that:
- is advanced or metastatic
- has a history of HER2-low or negative expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested)
- has HER2-low or HER2 IHC >0 <1+ expression
- was never previously HER2-positive
- is documented HR+ disease in the metastatic setting.
- No prior chemotherapy for advanced or metastatic breast cancer.
- Has adequate tumor samples for assessment of HER2 status
- Either disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting or disease progression within 24 months of starting adjuvant endocrine therapy and on at least 1 previous line of endocrine therapy in the metastatic setting
- Has protocol-defined adequate organ and bone marrow function
- Ineligible for all options in the investigator's choice chemotherapy arm
- Lung-specific intercurrent clinically significant illnesses
- Uncontrolled or significant cardiovascular disease or infection
- Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
- Patients with spinal cord compression or clinically active central nervous system metastases
- Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment
https://clinicaltrials.gov/ct2/show/NCT04494425.
Official Title: A Phase 1b/2 Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination With Other Anti-cancer Agents in Patients With HER2-positive Metastatic Breast Cancer (DESTINY-Breast07)
Primary Outcome Measures:
- Occurrence of adverse events (AEs)- Part 1 [ Time Frame: Up to follow-up period, approximately 40 months ]
- Occurrence of serious adverse events (SAEs)- Part 1 [ Time Frame: Up to follow-up period, approximately 40 months ]
- Occurrence of adverse events (AEs)- Part 2 [ Time Frame: Up to follow-up period, approximately 40 months ]
- Occurrence of serious adverse events (SAEs)- Part 2 [ Time Frame: Up to follow-up period, approximately 40 months ]
- Patients must be at least 18 years of age
-
Pathologically documented breast cancer that:
- Is advanced/unresectable (patients that can be treated with curative intent are not eligible) or metastatic
- HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local assessment
- Is documented as hormone receptor-positive (estrogen or progesterone receptor) or negative in the metastatic setting
- Patient must have adequate tumor sample for biomarker assessment
- ECOG Performance Status of 0 or 1
-
Part 1
- Disease progression on or after the last systemic therapy prior to starting study treatment
- At least 1 prior treatment line in metastatic setting required
- Part 2 a) No prior lines of therapy for advanced/MBC allowed
- Uncontrolled or significant cardiovascular disease
- Active or prior documented (non-infectious) ILD/pneumonitis that required steroids, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
- Lung-specific intercurrent clinically significant illnesses
- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- Spinal cord compression or a history of leptomeningeal carcinomatosis
- Prior treatment with immune checkpoint inhibitors
- Prior treatment with an ADC containing a topoisomerase I inhibitor
https://clinicaltrials.gov/ct2/show/NCT04538742.
Official Title: A Phase 1b Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination With Other Anti-cancer Agents in Patients With Metastatic HER2-low Breast Cancer (DESTINY-Breast08)
Primary Outcome Measures:
- Occurrence of adverse events (AEs)- Part 1 [ Time Frame: Up to follow-up period, approximately 24 months ]
- Occurrence of serious adverse events (SAEs)- Part 1 [ Time Frame: Up to follow-up period, approximately 24 months ]
- Occurrence of adverse events (AEs)- Part 2 [ Time Frame: Up to follow-up period, approximately 24 months ]
- Occurrence of serious adverse events (SAEs)- Part 2 [ Time Frame: Up to follow-up period, approximately 24 months ]
- Patients must be at least 18 years of age
-
Male or female patients who have pathologically documented breast cancer that:
- Has a history of HER2-low expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) with a validated assay
- Is documented as HR+ (either ER and/or PgR positive [ER or PgR ≥1%]) or ER and PgR negative (ER and PgR <1%) per ASCO/CAP guidelines in the metastatic setting
- Patient must have adequate tumor sample for biomarker assessment
- ECOG Performance Status of 0 or 1
- For patients with HR+ disease:
- For patients with HR- disease:
- Uncontrolled intercurrent illness
- Uncontrolled or significant cardiovascular disease
- History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- Lung-specific intercurrent clinically significant illnesses
- Has spinal cord compression or clinically active central nervous system metastases
- Active primary immunodeficiency
- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- Prior treatment with ADC that comprises of an exatecan derivative that is a topoisomerase I inhibitor.
https://clinicaltrials.gov/ct2/show/NCT04556773.
Official Title: Phase III Study of Trastuzumab Deruxtecan (T-DXd) With or Without Pertuzumab Versus Taxane, Trastuzumab and Pertuzumab in HER2-positive, First-line Metastatic Breast Cancer (DESTINY-Breast09)
Primary Outcome Measures:
- Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) assessment [Time Frame: Until progression or death, assessed up to approximately 60 months]
- Patients must be ≥18 years of age
-
Pathologically documented breast cancer that:
- is advanced or metastatic
- is locally assessed and prospectively centrally confirmed as HER2-positive (IHC3+ or ISH+)
- is documented by local testing as hormone receptor (HR)-positive or HR-negative disease in the metastatic setting
-
No prior chemotherapy or HER2-targeted therapy for advanced or metastatic breast cancer or only 1 previous line of endocrine therapy in the metastatic setting. Participants who have received chemotherapy or HER2-targeted therapy in the neo-adjuvant or adjuvant setting are eligible if > 6 months from treatment to metastatic diagnosis.
- Has protocol-defined adequate organ and bone marrow function
- Ineligible for any of the agents on the study.
- Any substance abuse or other medical conditions that, in the investigator's opinion, may interfere with subject's participation or study results.
- Patients with spinal cord compression or clinically active central nervous system metastases. Participants with clinically inactive brain metastases or treated brain metastases that are no longer symptomatic may be included in the study.
- Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
- Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment
https://clinicaltrials.gov/ct2/show/NCT04784715.
Official Title: An Open-Label, Multinational, Multicenter, Phase 3b/4 Study of Trastuzumab Deruxtecan in Patients With or Without Baseline Brain Metastasis With Previously Treated Advanced/Metastatic HER2-Positive Breast Cancer (DESTINY-Breast12)
Primary Outcome Measures:
-
Objective Response Rate (ORR) in Participants without BM at Baseline (Cohort 1) [ Time Frame: From screening until disease progression
(Up to 2.5 Years) ] - Progression-free Survival in Participants with BM at Baseline (Cohort 2) [ Time Frame: From screening until disease progression (Up to 2.5 Years) ]
- Participants should have pathologically documented breast cancer that is: unresectable/advanced or metastatic; confirmed HER2+ expression as determined to American Society of Clinical Oncology/College of American Pathologists guidelines
- Participant must have either: no evidence of BM, or untreated BM not needing immediate local therapy, or previously treated stable or progressing BM
- Participants with BM must be neurologically stable
-
Participants with stable BM or newly identified lesions found on contrast brain magnetic resonance imaging (MRI) performed during screening must be:
- ≥ 7 days since stereotactic radiosurgery or gamma knife
- ≥ 21 days since whole brain radiotherapy
- ECOG performance status 0-1
- Radiologic or objective evidence of disease progression on trastuzumab, pertuzumab, or T-DM1 (≤ 2 lines/regimens of therapy in the metastatic setting)
- At least 1 lesion that can be accurately measured at baseline as ≥ 10 mm in the longest diameter with computed tomography (CT) or MRI and is suitable for accurate repeated measurements; or non-measurable CNS disease; or nonmeasurable, bone-only disease that can be assessed by CT or MRI or X-Ray. Lytic or mixed lytic bone lesions that can be assessed by CT or MRI or X-ray in the absence of measurable disease as defined above is acceptable; Participants with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible
- Adequate organ and bone marrow function within 14 days before the day of first dosing as defined in the protocol
- left ventricular ejection fraction ≥50% within 28 days before enrollment
- Negative pregnancy test (serum) for women of childbearing potential
- Known or suspected leptomeningeal disease
- Prior exposure to tucatinib treatment
- A pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy
- Refractory nausea and vomiting, chronic gastrointestinal disease, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of T-DXd
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence
- Persistent toxicities (CTCAE Grade >2) caused by previous anticancer therapy, excluding alopecia
- Based on screening brain MRI, participants must not have any of the following: Any untreated brain lesions > 2.0 cm in size; ongoing use of systemic corticosteroids for control of symptoms of BM; any brain lesion thought to require immediate local therapy; Have poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to BM not withstanding CNS-directed therapy
- Has spinal cord compression
- Known active hepatitis B or C infection, positive hepatitis C antibody, hepatitis B virus surface antigen, or hepatitis B virus core antibody at screening
- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- Receipt of live, attenuated vaccine within 30 days prior to the first dose of T-DXd
- Participants with a medical history of myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV)
- History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
- Lung-specific intercurrent clinically significant illnesses and any autoimmune, connective tissue or inflammatory disorders
- Prior exposure, without adequate treatment washout period before randomization/enrollment, to chloroquine/hydroxychloroquine: < 14 days
- Immunotherapy (non-antibody-based therapy), retinoid therapy, hormonal therapy: < 3 weeks
- < 6 weeks for nitrosoureas or mitomycin
- < 1 week for tyrosine kinase inhibitor (TKIs) approved for the treatment of non-small cell lung cancer - baseline CT scan must be completed after discontinuation of TKI
- Antibody-based anticancer therapy: < 4 weeks
- Any concurrent anticancer treatment. Concurrent use of hormonal therapy for noncancer- related conditions is allowed
- Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks before the first dose of study intervention
- Participants with prior exposure to immunosuppressive medication within 14 days prior to first study dose
- Participants with a known hypersensitivity to study intervention or any of the excipients of the product or other monoclonal antibodies
https://clinicaltrials.gov/ct2/show/NCT04739761.
This website reflects investigational compounds and/or investigational uses of approved products. The safety and efficacy of these investigational agents or investigational uses of approved products has not been established. Any approved products should be used in accordance with their product labeling (or Prescribing Information).
About trastuzumab deruxtecan (T-DXd)*
T-DXd is currently being studied for a number of potential uses, including certain types of cancers including breast, gastric, lung, and additional cancer types.
Find a Trial Location
This website has a search feature to find trial locations in some of the participating countries.
This website has a search feature to find trial locations in some of the participating countries.
The information provided is intended for potential clinical investigators and other interested healthcare professionals who may wish to enroll or refer patients to clinical trials.
*Known in the U.S. as fam-trastuzumab deruxtecan-nxki and formerly known as DS-8201a.
ADC, antibody-drug conjugate; AEs, adverse events; ASCO-CAP, American Society of Clinical Oncology-College of American Pathologists; BC, breast cancer; BICR, blinded independent central review; BM, brain metastasis; CDK, cyclin-dependent kinase; CHF, congestive heart failure; CIS, carcinoma in situ; CNS, central nervous system; COPD, chronic obstructive pulmonary disease; CT, computed tomography; CTCAE, Common Terminology Criteria for Adverse Events; ECOG, Eastern Cooperative Oncology Group; ER, estrogen receptor; ET, endocrine therapy; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IDFS, invasive disease-free survival; IHC, immunohistochemistry; ILD, interstitial lung disease; ISH, in situ hybridization; LCIS, lobular carcinoma in situ; LVEF, left ventricular ejection fraction; MBC, metastatic breast cancer; MI, myocardial infarction; MRI, magnetic resonance imaging; mTOR, mechanistic target of rapamycin; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NCT, national clinical trial; ORR, objective response rate; PFS, progression free survival; PgR/PR, progesterone receptor; PI3-K, phosphoinositide 3-kinase; RECIST, Response Evaluation Criteria in Solid Tumors; SAEs, serious adverse events; T-DM1, trastuzumab emtansine; T-DXd, fam-trastuzumab deruxtecan-nxki; TKI, tyrosine kinase inhibitor.
Studies for patients whose primary cancer site originated in the stomach.
Select a clinical trial below to learn more.
Official Title: A Phase 1b/2 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of Trastuzumab Deruxtecan (T-DXd) Monotherapy and Combinations in Adult Participants With HER2 Overexpressing Gastric Cancer (DESTINY-Gastric03)
Primary Outcome Measures:
- Part 1: Occurrence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Safety will be assessed for approximately 24 months from informed consent. ]
- Part 2: Objective Response Rate (ORR) [ Time Frame: An average of approximately 12 months. ]
- Male and female participants must be at least 18 years of age
- Disease Characteristics: Locally advanced, unresectable, or metastatic disease Pathologically documented adenocarcinoma of the stomach or GEJ with HER2 overexpression (IHC 3+ or ICH 2+/ISH+)
- For Part 1, progression on or after at least one prior trastuzumab containing regimen. For Part 2, previously untreated for unresectable or metastatic adenocarcinoma of the stomach or GEJ with HER2 overexpression.
- Has measurable target disease assessed by the Investigator based on RECIST version 1.1
- Has protocol defined adequate organ function including cardiac, renal and hepatic function
- If of reproductive potential, agrees to use a highly effective form of contraception or avoid intercourse during and upon completion of the study.
- History of active primary immunodeficiency, known HIV, active HBV or HCV infection.
- Uncontrolled intercurrent illness
- History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening
- Lung-specific intercurrent clinically significant severe illnesses
- Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals
- Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).
- Has spinal cord compression or clinically active central nervous system metastases.
https://clinicaltrials.gov/ct2/show/NCT04379596.
Official Title: A Phase 3, Multicenter, 2-Arm Randomized, Open-Label Study of Trastuzumab Deruxtecan in Subjects With HER2-Positive Metastatic and/or Unresectable Gastric or Gastro-Esophageal Junction (GEJ) Adenocarcinoma Subjects Who Have Progressed on or After a Trastuzumab-Containing Regimen (DESTINY-Gastric04)
Primary Outcome Measures:
- Overall Survival in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel [ Time Frame: Time from date of randomization until death (due to any cause), up to approximately 36 months ]
- Adults (according to local regulation) and able to provide informed consent for study participation.
- Pathologically documented gastric or GEJ adenocarcinoma that has been previously treated in the metastatic setting (unresectable, locally advanced, or metastatic disease).
- Progression on or after first-line therapy with a trastuzumab or approved trastuzumab biosimilar-containing regimen. Note: Prior adjuvant therapy with a trastuzumab-containing regimen can be counted as a line of therapy if the subject progressed on or within 6 months of completing adjuvant therapy.
- Centrally confirmed HER2-positive (IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH) as classified by ASCO-CAP on a tumor biopsy obtained after progression on or after a first-line trastuzumab or approved trastuzumab biosimilar-containing regimen.
- Eastern Cooperative Oncology Group performance status of 0 or 1 at both Screening and within 3 days prior to randomization.
- Adequate bone marrow, renal, and hepatic function within 14 days of randomization.
- Use of anticancer therapy after trastuzumab-containing treatment
- Medical history of myocardial infarction (MI) within 6 months before randomization/enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV).
- Has a QT interval corrected by Fridericia's formula (QTcF) prolongation to >470 msec (female subjects) or >450 msec (male subjects) based on average of the Screening triplicate12-lead ECG.
- Has a pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART). Drainage and CART must be at least 2 weeks prior to Screening.
- Has a history of (non-infectious) interstitial lung disease (ILD/pneumonitis) that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
- Any autoimmune, connective tissue or inflammatory disorders (eg, rheumatoid arthritis, Sjögren syndrome, sarcoidosis, etc.) where there is documented (or a suspicion of) pulmonary involvement at the time of Screening.
- Prior pneumonectomy.
- Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
- Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated.
- History of severe hypersensitivity reactions to either the T-DXd or inactive ingredients in T-DXd.
- History of severe hypersensitivity reactions to other monoclonal antibodies or any components used in the ramucirumab drug product preparation
- Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy such as peripheral neuropathy, Grade 2.
- Current uncontrolled infection requiring antibiotics, antivirals, or antifungals or an unexplained fever >38.0°C during Screening visits or on the first scheduled day of dosing (at the discretion of the Investigator, participants with tumor fever may be enrolled), which in the Investigator's opinion might compromise the participant's participation in the study or affect the study outcome
- Clinically significant gastrointestinal disorder (eg, including hepatic disorders, bleeding, inflammation, occlusion, ileus, diarrhea Grade >1, jaundice, intestinal paralysis, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, or partial bowel obstruction) in the opinion of Investigator
https://clinicaltrials.gov/ct2/show/NCT04704934.
This website reflects investigational compounds and/or investigational uses of approved products. The safety and efficacy of these investigational agents or investigational uses of approved products has not been established. Any approved products should be used in accordance with their product labeling (or Prescribing Information).
About trastuzumab deruxtecan (T-DXd)*
T-DXd is currently being studied for a number of potential uses, including certain types of cancers including breast, gastric, lung, and additional cancer types.
Find a Trial Location
This website has a search feature to find trial locations in some of the participating countries.
This website has a search feature to find trial locations in some of the participating countries.
The information provided is intended for potential clinical investigators and other interested healthcare professionals who may wish to enroll or refer patients to clinical trials.
*Known in the U.S. as fam-trastuzumab deruxtecan-nxki and formerly known as DS-8201a.
AEs, adverse events; ASCO-CAP, American Society of Clinical Oncology-College of American Pathologists; CART, concentrated ascites reinfusion therapy; ECG, electrocardiogram; GEJ, gastroesophageal junction; HBV, hepatitis B virus; HCV, hepatitis C virus; HER2, human epidermal growth factor receptor 2; HIV, human immunodeficiency virus; IHC, immunohistochemistry; ILD, interstitial lung disease; ISH, in situ hybridization; IV, intravenous; MI, myocardial infarction; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NCT, national clinical trial; ORR, objective response rate; OS, overall survival; QTcF, QT interval corrected by Fridericia's formula; RECIST, Response Evaluation Criteria in Solid Tumors; SAEs, serious adverse events;
T-DXd, fam-trastuzumab deruxtecan-nxki.
Studies for patients whose primary cancer site originated in the lung.
Select a clinical trial below to learn more.
Official Title: A Phase 2, Multicenter, Randomized Study of Trastuzumab Deruxtecan in Subjects With HER2-mutated Metastatic
Non-small Cell Lung Cancer (NSCLC) (DESTINY-Lung02)
Primary Outcome Measures:
- Objective Response Rate by Blinded Independent Central Review Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors [ Time Frame: 9 months after the last participant is randomized or later, up to approximately 31 months ]
- Written informed consent
- Men or women ≥18 years, follow local regulatory requirements if the legal age of the consent for study participation is >18 years
- Pathologically documented metastatic NSCLC with a known activating HER2 mutation. Note: A HER2 mutation documented only from a liquid biopsy samples cannot be used for enrollment.
- Had previous treatment (second line or later [2L+], including platinum therapy), not amenable to curative surgery or radiation
- Presence of at least 1 measurable lesion confirmed by the blinded Independent Central Review based on RECIST version 1.1
- Willing and able to provide an archival tumor tissue sample. A fresh biopsy is required if an archival tumor tissue sample cannot be supplied. Fine needle aspirates are not acceptable.
- Eastern Cooperative Oncology Group performance status 0 to 1
- Left ventricular ejection fraction ≥ 50% within 28 days before randomization
- Adequate organ function as specified in protocol within 14 days before randomization
- Adequate treatment washout period before randomization
- Participants of reproductive/childbearing potential agree to use a highly effective form of contraception (or avoid intercourse) during study period and up to 7 months (females) and 4 months (males) after last study dose
- Males should not freeze or donate sperm throughout the study period up to at least 4 months after last study dose; females should not donate or retrieve ova for their own use throughout the study period and up to at least 7 months after last study dose
- Life expectancy 3 months or more
- Known driver mutation in the epidermal growth factor receptor (EGFR) or BRAF gene or a known anaplastic lymphoma kinase (ALK) or ROS1 fusion
- Medical history of myocardial infarction within 6 months before randomization, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Participants with troponin levels above upper limit of normal at screening (as defined by the manufacturer) and without any myocardial infarction (MI)-related symptoms should have a cardiologic consultation before enrollment to rule out MI
- Corrected QT interval (QTcF) prolongation > 470 msec (females) or >450 msec (males) based on average of the triplicate12-lead electrocardiogram at screening
- History of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
- Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
- Multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated
- History of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product
- History of severe hypersensitivity reactions to other monoclonal antibodies
- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- Substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the participant's participation in the clinical study or evaluation of the clinical study results
- Known human immunodeficiency virus (HIV) infection
- Known active, clinically relevant liver disease (eg, active hepatitis B, or active hepatitis C), based on available blood tests, liver ultrasound, or liver biopsy results
- Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline
- Pregnant, breastfeeding, or planning to become pregnant
- Otherwise considered inappropriate for the study by the Investigator
- Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg. pulmonary emboli within three months of the study randomization, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc.)
- Any autoimmune, connective tissue or inflammatory disorders (e.g., Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening
- Prior complete pneumonectomy
https://clinicaltrials.gov/ct2/show/NCT04644237.
Official Title: A Phase Ib Multicenter, Open-label Dose-escalation Study to Evaluate the Safety and Tolerability of Trastuzumab Deruxtecan (T-DXd) and Durvalumab in Combination With Cisplatin, Carboplatin or Pemetrexed in First-line Treatment of Patients With Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) and Human Epidermal Growth Factor Receptor 2 Overexpression (HER2+) (DESTINY-Lung03)
Primary Outcome Measures:
- Frequency of AEs and SAEs [ Time Frame: Safety will be assessed for approximately 20 months from informed consent ]
- Histologically documented locally advanced/metastatic non-squamous NSCLC
- Patients must have tumors that lack activating EGFR mutations, EML4-ALK fusion, and ROS-1 mutation
- Patients must be treatment- naïve for locally advanced or mNSCLC and medically fit to receive first-line treatment. Prior adjuvant, neo adjuvant therapies are permitted if progression has occurred > 12 months from the end of last therapy
- HER2+ (IHC 3+ or IHC 2+) status as determined by central review of tumor tissue
- WHO / ECOG performance status of 0 or 1
- Has a measurable target disease assessed by the investigator using RECIST 1.1
- Has a protocol defined adequate organ and bone marrow functions
- Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
- Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder and prior pneumonectomy
- Active primary immunodeficiency known HIV infection, or active hepatitis B or C infection
- Active infection including tuberculosis and uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
- Medical history of myocardial infarction within 6 months before treatment assignment, symptomatic CHF (New York Heart Association Class II to IV), clinically important cardiac arrhythmias, or a recent (< 6 months) cardiovascular event including stroke
- A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or CART
https://clinicaltrials.gov/ct2/show/NCT04686305.
This website reflects investigational compounds and/or investigational uses of approved products. The safety and efficacy of these investigational agents or investigational uses of approved products has not been established. Any approved products should be used in accordance with their product labeling (or Prescribing Information).
About trastuzumab deruxtecan (T-DXd)*
T-DXd is currently being studied for a number of potential uses, including certain types of cancers including breast, gastric, lung, and additional cancer types.
Find a Trial Location
This website has a search feature to find trial locations in some of the participating countries.
This website has a search feature to find trial locations in some of the participating countries.
The information provided is intended for potential clinical investigators and other interested healthcare professionals who may wish to enroll or refer patients to clinical trials.
*Known in the U.S. as fam-trastuzumab deruxtecan-nxki and formerly known as DS-8201a.
2L, second line; AEs, adverse events; ALK, anaplastic lymphoma kinase; BICR, blinded independent central review; BRAF; v-raf murine sarcoma viral oncogene homologue B1; CART, concentrated ascites reinfusion therapy; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; CR, complete response; ECOG, Eastern Cooperative Oncology Group; EGFR, epidermal growth factor receptor; HER2, human epidermal growth factor receptor 2; HIV, human immunodeficiency virus; IHC, immunohistochemistry; ILD, interstitial lung disease; IV, intravenous; MI, myocardial infarction; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NCT, national clinical trial; NSCLC, non-small cell lung cancer; ORR, objective response rate; PR, partial response; QTcF, QT interval corrected by Fridericia's formula; RECIST, Response Evaluation Criteria in Solid Tumors; SAEs, serious adverse events; T-DXd, fam-trastuzumab deruxtecan-nxki; WHO, World Health Organization.
Pan-tumor: Studies that include patients with various cancer types.
Colorectal (CRC): Studies for patients whose primary cancer site originated in the colon or rectum.
Select a clinical trial below to learn more.
Official Title: A Phase II, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd) for the Treatment of Unresectable and/or Metastatic Solid Tumors Harboring HER2 Activating Mutations Regardless of Tumor Histology
Primary Outcome Measures:
- Confirmed objective response rate by RECIST 1.1 based on independent central review (ICR). [ Time Frame: An average of approximately 12 months. ]
- Adults ≥18 years old. Other age restrictions may apply as per local regulations.
- Unresectable and/or metastatic solid tumors with pre-specified HER2 mutations locally determined by NGS, who have progressed following prior treatment or who have no satisfactory alternative treatment options.
- Prior HER2 targeted therapy is permitted.
- All patients must provide an FFPE tumor sample for retrospective central HER2 testing.
- LVEF ≥50%
- ECOG 0-1
- HER2 overexpressing (IHC3+ or IHC2+/ISH+) breast, gastric or gastroesophageal junction adenocarcinoma.
- HER2 mutant NSCLC.
- History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD cannot be ruled out by imaging at screening
- Lung-specific intercurrent clinically significant severe illnesses.
- History of active primary immunodeficiency, known HIV, active HBV or HCV infection
- Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals
- Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).
- Has spinal cord compression or clinically active central nervous system metastases.
https://clinicaltrials.gov/ct2/show/NCT04639219.
Official Title: A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd, DS-8201a) for the Treatment of Selected HER2 Expressing Tumors (DESTINY-PanTumor02)
Primary Outcome Measures:
- Objective Response Rate (ORR) [ Time Frame: An average of approximately 12 months ]
- Locally advanced, unresectable, or metastatic disease based on most recent imaging.
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The respective cohorts for patient inclusion are:
- Cohort 1: Biliary tract cancer
- Cohort 2: Bladder cancer
- Cohort 3: Cervical cancer
- Cohort 4: Endometrial cancer
- Cohort 5: Epithelial ovarian cancer
- Cohort 6: Pancreatic cancer
- Cohort 7: Rare tumors: This cohort will consist of patients with tumors that express HER2, excluding the tumors mentioned above, and breast, non-small cell lung cancer, gastric cancer, and colorectal cancer.
- Progressed following prior treatment or who have no satisfactory alternative treatment option.
- Prior HER2 targeting therapy is permitted.
- HER2 expression for eligibility may be based on local or central assessment.
- Has measurable target disease assessed by the Investigator based on RECIST version 1.1.
- Has protocol- defined adequate organ function including cardiac, renal and hepatic function.
- Uncontrolled intercurrent illness
- History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD that cannot be ruled out by imaging at screening
- Lung-specific intercurrent clinically significant severe illnesses
- Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals
- Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART)
- Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression.
- Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small cell lung cancer.
https://clinicaltrials.gov/ct2/show/NCT04482309.
Official Title: A Phase 2, Multicenter, Randomized, Study of Trastuzumab Deruxtecan in Participants With HER2-overexpressing Locally Advanced, Unresectable or Metastatic Colorectal Cancer (DESTINY-CRC02)
Primary Outcome Measures:
- Change in Confirmed Objective Response Rate by Blinded Independent Central Review Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Human epidermal growth factor receptor 2-overexpressing Metastatic Colorectal Cancer [ Time Frame: The first 80 participants have 12 weeks of follow-up or have discontinued the treatment for the Interim Analysis (IA), 6 months after the last participant is registered for the primary analysis ]
Participants must meet all of the following criteria to be eligible for randomization/registration into the study:
- Adults aged ≥20 years in Japan, Taiwan, and Korea, or those aged ≥18 years in other countries, at the time the Informed Consent Forms (ICFs) are signed.
- Pathologically-documented, unresectable, recurrent, or metastatic colorectal adenocarcinoma. Participants must have v-raf murine sarcoma viral oncogene homologue B1 (BRAF) wild-type cancer and rat sarcoma viral oncogenes homologue (RAS) status identified in primary or metastatic site.
-
The following therapies should be included in prior lines of therapy:
- Fluoropyrimidine, oxaliplatin, and irinotecan, unless contraindicated
- Anti-epidermal growth factor receptor (EGFR) treatment, if RAS wild-type and if clinically indicated
- Anti-vascular endothelial growth factor (VEGF) treatment, if clinically indicated
- Anti-programmed death ligand 1 (PD-(L)-1) therapy, if the tumor is microsatellite instability (MSI)-high/deficient mismatch repair (dMMR), or tumor mutational burden (TMB)-high, if clinically indicated
- Confirmed human epidermal growth factor 2 (HER2)-overexpressing status assessed by central laboratory and defined as immunohistochemistry (IHC) 3+ or IHC 2+/ in situ hybridization (ISH)+.
- Presence of at least one measurable lesion assessed by the Investigator per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
- Has left ventricular ejection fraction (LVEF) ≥50% within 28 days before randomization/registration.
Participants who meet any of the following criteria will be disqualified from entering the study:
- Medical history of myocardial infarction (MI) within 6 months before randomization/registration, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Participants with troponin levels above the upper limit of normal (ULN) at Screening (as defined by the manufacturer), and without any MI-related symptoms, should have a cardiologic consultation before randomization/registration to rule out MI.
- Has a corrected QT interval corrected with Fridericia's formula (QTcF) prolongation to >470 msec (female participants) or >450 msec (male participants) based on the average of the Screening triplicate 12-lead electrocardiograms (ECGs).
- Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
- Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the randomization/registration, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc.).
- Any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid arthritis, Sjögren syndrome, sarcoidosis, etc.) where there is documented, or a suspicion of, pulmonary involvement at the time of Screening.
- Prior pneumonectomy.
- Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole-brain radiotherapy and randomization/registration.
- Participants with leptomeningeal carcinomatosis.
- Has known human immunodeficiency virus (HIV) infection.
-
Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days before study randomization/registration. Participants with past or resolved hepatitis B virus (HBV) infection are eligible if hepatitis B surface antigen (HBsAg) negative (-) and antibody to hepatitis B core antigen (anti-HBc) positive (+).
Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA). - Previous treatment with a DXd-containing antibody-drug conjugate (ADC).
https://clinicaltrials.gov/ct2/show/NCT04744831.
This website reflects investigational compounds and/or investigational uses of approved products. The safety and efficacy of these investigational agents or investigational uses of approved products has not been established. Any approved products should be used in accordance with their product labeling (or Prescribing Information).
About trastuzumab deruxtecan (T-DXd)*
T-DXd is currently being studied for a number of potential uses, including certain types of cancers including breast, gastric, lung, and additional cancer types.
Find a Trial Location
This website has a search feature to find trial locations in some of the participating countries.
This website has a search feature to find trial locations in some of the participating countries.
The information provided is intended for potential clinical investigators and other interested healthcare professionals who may wish to enroll or refer patients to clinical trials.
*Known in the U.S. as fam-trastuzumab deruxtecan-nxki and formerly known as DS-8201a.
ADC, antibody-drug conjugate; BICR, blinded independent central review; BRAF; v-raf murine sarcoma viral oncogene homologue B1; CART, concentrated ascites reinfusion therapy; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; CR, complete response; CRC, colorectal cancer; dMMR, deficient mismatch repair; ECGs, electrocardiograms; EGFR, epidermal growth factor receptor; ECOG PS, Eastern Cooperative Oncology Group performance status; ERBB2, erb-b2 receptor tyrosine kinase 2; FFPE, formalin-fixed paraffin-embedded; HBV, hepatitis B virus; HCV, hepatitis C virus; HER2, human epidermal growth factor receptor 2; HBsAg, hepatitis B surface antigen; HBc, hepatitis B core; HIV, human immunodeficiency virus; IA, interim analysis; ICFs, informed consent forms; ICR, indepent central review; IHC, immunohistochemistry; ILD, interstitial lung disease; ISH, in situ hybridization; IV, intravenous; LVEF, left ventricular ejection fraction; MI, myocardial infarction; MSI, microsatellite instability; NCT, national clinical trial; NGS, next generation sequencing; NSCLC, non-small cell lung cancer; ORR, objective response rate; PR, partial response; QTcF, QT interval corrected by Fridericia's formula; RAS, rat sarcoma viral oncogenes homologue; RECIST, Response Evaluation Criteria in Solid Tumors; RNA, ribonucleic acid; T-DXd, fam-trastuzumab deruxtecan-nxki; TMB, tumor mutational burden; ULN, upper limit of normal; VEGF, vascular endothelial growth factor.
This website reflects investigational compounds and/or investigational uses of approved products. The safety and efficacy of these investigational agents or investigational uses of approved products has not been established. Any approved products should be used in accordance with their product labeling (or Prescribing Information).
What Is a Clinical Trial?
Clinical trials are part of clinical research that look at new ways to prevent, detect, or treat disease. Clinical trials can help to determine if new medicines are tolerated and effective. They are important as they, in many cases, may lead to medical advances and further understanding of potential treatment options for people. To participate in a clinical trial, people must volunteer at a participating trial location. Your doctor can explain the risks and benefits to you to help you determine if a trial is right for you as well as help you enroll.
*Known in the U.S. as fam-trastuzumab deruxtecan-nxki and formerly known as DS-8201a.
This website contains detailed medical information, but is intended
for both patients and healthcare professionals.