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New drug DS-8201a shows promise in targeting Hard-to-Treat cancers

NCT ID NCT04294628

What the study statuses mean

This study's is highlighted.

Recruitment status, easiest to join first

Recruiting now
This trial is taking on new participants right now.
Not yet recruiting
Registered, but not yet taking participants.
By invitation only
Not open to general applications. Only people the study team invites can take part.
Paused
Paused for now. It may or may not start again.
Ongoing This study
Running, but no longer taking on new participants.
Completed
The trial has finished. Results may not be published yet.
Stopped early
Stopped early, before it reached the end. That can be for many reasons, including safety.
Cancelled
Cancelled before anyone took part.

Expanded access (not trials)

Expanded access
Not a trial. This treatment can be requested outside a study, case by case, for people who qualify.
Expanded access (paused)
Not a trial. The treatment can normally be requested outside a study, but is unavailable right now.
Expanded access (ended)
Not a trial. The treatment could once be requested outside a study, but no longer can.
Approved
The treatment has been approved, so it is available normally rather than through this programme.

When the status isn't known

Details not published
The full record has not been published yet, so there is little to show here.
Status unknown
This status has not been confirmed recently, so it may be out of date.

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This early-phase trial is testing a drug called DS-8201a in 62 adults with advanced HER2-positive solid tumors that have not responded to standard treatments. The drug works by attaching to the HER2 protein on cancer cells and damaging their DNA, which may kill the cells. Researchers will take tumor samples before and after treatment to see how the drug affects proteins and immune cells in the tumor.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance
DS-8201a (a drug that targets HER2 protein on cancer cells and damages their DNA)
What this could lead to
If successful, this could help develop better treatments for advanced HER2-positive cancers that have stopped responding to standard therapies.
What could go wrong
This is a very early (Phase 1) pilot study with only 62 participants, so results may not apply to all patients. The drug may not work as hoped or could cause side effects.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1

The first testing in people. Mainly checks safety and dose, usually in a small group.

Participants

62 people

The number who actually took part.

Started

Sep 2020

Expected to finish

Jan 2027

An estimate. End dates often move.

Lead sponsor

A government research agency

The lead sponsor is the US National Institutes of Health.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective * Patients must have measurable or evaluable disease * Age \>= 18 years of age * Patients must have HER2-positive or HER2-expressing tumors as defined by Clinical Laboratory Improvement Act (CLIA)-certified labs. Patients must have either: * A tumor HER2 immunohistochemistry (IHC) score of 1+ or greater (as determined by a CLIA-certified IHC test, per criteria specified) or * A tumor with HER2 amplification (as determined by CLIA-certified in situ hybridization \[ISH\] or a CLIA-certified next-generation sequencing assay) * Patients with HER2 mutations are eligible, as are patients with HER2-positive breast cancer * Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%) * Absolute neutrophil count \>= 1,500/mcL (within 8 days of enrollment) * Platelets \>= 100,000/mcL (within 8 days of enrollment) * Leukocytes \>= 3,000/mcL (within 8 days of enrollment) * Hemoglobin \>= 9 g/dL (\>= 8.0 g/dL for gastric cancer \[GC\] only) (within 8 days of enrollment) * Serum albumin \>= 2.5 g/dL (GC only) (within 8 days of enrollment) * Total bilirubin =\< 1.5 x institutional upper limit of normal (=\< 3 x upper limit of normal in the presence of documented Gilbert's syndrome or liver metastases at baseline) (within 8 days of enrollment) * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal OR =\< 5 x institutional upper limit of normal for patients with liver metastases at baseline (within 8 days of enrollment) * Creatinine =\< 1.5 x institutional upper limit of normal OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above 1.5 x institutional normal (within 8 days of enrollment) * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment * No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1 week prior to screening assessment * International normalized ratio (INR)/prothrombin time (PT) and either partial thromboplastin or activated partial thromboplastin time (aPTT) =\< 1.5 x upper limit of normal (ULN) * Ability to understand and the willingness to sign a written informed consent document * Willingness to provide blood samples for research purposes * Patients must have a lesion or lesions amenable to biopsy and must be willing to undergo 3 core needle biopsy procedures for research purposes * Patients must have left ventricular ejection fraction (LVEF) \>= 50% by either an echocardiogram (ECHO), multigated acquisition (MUGA), or cardiac MRI scan within 28 days prior to enrollment * Patients receiving standard of care androgen deprivation treatment (surgical castration versus luteinizing hormone-releasing hormone \[LHRH\] agonist or antagonist treatment) are eligible to participate in the trial. Patients receiving LHRH agonist or antagonist may continue treatment throughout the duration of this study * Patients who are human immunodeficiency virus (HIV) positive may participate IF they meet the following eligibility requirements: * They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective * They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count \< 200 cells/uL over the past 2 years, unless it was deemed related to the cancer and/or immunotherapy-induced bone marrow suppression * For patients who have received chemotherapy in the past 6 months, a CD4 count \< 250 cells/ul during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy * They must have an undetectable viral load and a CD4 count \>= 250 cells/uL within 8 days of enrollment * They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months HIV-infected patients should be monitored every 12 weeks for viral load and CD4 counts * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for \>= 1 month after treatment of the brain metastases * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * The effects of DS-8201a on the developing human fetus are unknown. For this reason and because HER2 antibodies conjugated to topoisomerase 1 inhibitor agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation and for at least 7 months after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of DS-8201a administration * Women of non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \[FSH\] \> 40 mIU/mL and estradiol \< 40 pg/mL \[\< 147 pmol/L\] is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method * Subjects must not freeze, donate, or retrieve for their own use ova or sperm starting at screening, throughout the study period, and for at least 4.5 months after the final study drug administration. Preservation of sperm or ova should be considered prior to enrollment in this study * Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with DS-8201a, breastfeeding should be discontinued if the mother is treated with DS-8201a Exclusion Criteria: * Patients who have had: * Chemotherapy (including antibody drug therapy, retinoid therapy, hormonal therapy for cancer-with the exception of standard of care androgen deprivation treatment) within: * 4 weeks or five half-lives, whichever is shorter, for small-molecule targeted agents such as 5-fluorouracil-based agents, folinate agents, weekly paclitaxel or * 6 weeks for nitrosoureas or mitomycin C or * Immunotherapy, including monoclonal antibody therapy, within 4 weeks * Patients with any of the following pulmonary-related illnesses: * A history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or for whom suspected ILD/pneumonitis cannot be ruled out by imaging at screening * Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease \[COPD\] grade 3-4 per Global Initiative for Obstructive Lung Disease \[GOLD\] criteria, restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement (i.e., Rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy * Patients who have had radiation therapy within 4 weeks (or palliative stereotactic radiation therapy within 2 weeks) * Patients who have had a major surgery within 4 weeks * Patients who are receiving any other investigational agents * Patients with a medical history of myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association class II to IV), or with troponin levels consistent with myocardial infarction (as defined according to the assay manufacturer) 28 days prior to enrollment * History of allergic reactions attributed to compounds of similar chemical or biologic composition to DS-8201a (e.g., other topoisomerase I inhibitors) or the inactive ingredients in the drug product * Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies * Patients with a Fridericia's formula-corrected QT interval (QTcF) prolongation to \> 470 ms (females) or \> 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG) * Patients with 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 * Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals * Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade =\< 1 or baseline. Subjects with chronic grade 2 toxicities (e.g., grade 2 chemotherapy-induced neuropathy) may be eligible per the discretion of the investigator after consultation with the sponsor medical monitor or designee. Subjects should no longer be symptomatic nor require treatment with corticosteroids or anticonvulsants and must have recovered from the acute toxic effect of radiotherapy * Patients with substance abuse or any other medical conditions that would increase the safety risk to the subject or interfere with participation of the subject or evaluation of the clinical study in the opinion of the investigator * Patients with uncontrolled intercurrent illness * Patients with psychiatric illness/social situations that would limit compliance with study requirements * Pregnant women are excluded from this study because DS-8201a is a HER2 antibody conjugated to a topoisomerase 1 inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with DS-8201a, breastfeeding should be discontinued if the mother is treated with DS-8201a * Patients are not allowed to receive chloroquine/hydroxychloroquine. Patients receiving chloroquine/hydroxychloroquine require a washout of \> 14 days

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Conditions

The condition(s) this trial relates to.

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Contacts and locations

Locations

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215, United States

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065, United States

  • National Cancer Institute Developmental Therapeutics Clinic

    Bethesda, Maryland, 20892, United States

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892, United States

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210, United States

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232, United States

More trials for these conditions

Other studies related to the condition(s) this trial covers.