AzTrials
AzTrials

Metastatic Malignant Solid NeoplasmPhase 1NCT05372614

Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene

A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Metastatic Malignant Solid Neoplasm and Metastatic Pancreatic Adenocarcinoma, run by National Cancer Institute (NCI) at 18 sites in United States.

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Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This phase I trial tests the safety, side effects, and best dose of neratinib in combination with trastuzumab deruxtecan in treating patients with solid tumors that have spread from where it first started (primary site) to other places in the body (metastatic) or that cannot be removed by surgery (unresectable), and… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy Procedure, Biospecimen Collection and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
18 sitesUnited States
Study dates
5 Oct 2022to 17 Jul 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically confirmed malignancy that is metastatic or unresectable with participation in this clinical trial determined to be the best option for next treatment in the opinion of the investigator, and meet the following specific criteria:
  • Patients enrolling in Part 1 (Dose Escalation) may have a diagnosis of any solid tumor
  • Patients enrolling in the Part 2 Pharmacodynamic Cohort may have a diagnosis of any solid tumor except pancreas cancer (NOTE: pancreatic cancer excluded from this cohort after Revision 11 activation due to the addition of the pancreatic specific cohort)
  • Patients enrolling in the Part 2 Pancreatic Cohort must have a diagnosis of pancreatic adenocarcinoma (PDAC) and meet the HER2 positivity guidance
  • Patients must have a solid tumor with HER2-positivity as determined by any one or more of the following:
  • HER2 overexpression defined by immunohistochemistry (IHC) 3+
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  • ERBB2 amplification by in situ hybridization (ISH) or next-generation sequencing as determined by any Clinical Laboratory Improvement Act (CLIA) certified lab
  • A known HER2 activating mutation
  • HER2 overexpression by IHC/ISH will follow histology specific American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines for breast and gastric cancers. HER2 overexpression by IHC/ISH for the Pancreatic Cohort will follow ASCO-CAP guidelines for gastric cancers. For tumor histologies without specific guidelines the following criteria will apply:
  • HER2 IHC should be performed first, followed by ISH methods in cases showing 2+ (equivocal) expression by IHC. Positive (IHC 3+) or negative (IHC 0 or 1+) do not require further ISH testing. Cases with HER2:CEP17 ratio ≥ 2 or an average HER2 copy number ≥ 6.0 signals per cell are considered positive by ISH
  • Known HER2 activating mutations:
  • G309A/E
  • S310F/Y
  • S653C
  • V659E
  • G660D
  • R678Q
  • E693K
  • Q709L
  • L755S/P
  • Del. 755-759
  • D769Y/H
  • G776V/C
  • V777L
  • V842I
  • T862A
  • L869R
  • H878Y
  • All exon 20 insertions, including:
  • A771_Y772insYVMA
  • A775_G776insYVMA
  • Y772_A775dup
  • P780_Y781insGSP
  • G778_P780dup
  • V697L
  • T733I
  • D769N
  • L841V
  • L866M
  • R896C
  • If a different mutation is identified, contact the study chair for conferral. Synonymous mutations are not eligible
  • Patients must have received at least 1 prior line of therapy in the advanced/metastatic setting. No limitation on number of prior therapies; however, patients may not have received neratinib or DS-8201a previously. Prior HER2-targeted therapy other than neratinib or DS-8201a is allowed (e.g., trastuzumab, pertuzumab, TDM-1, lapatinib, etc.)
  • Age >= 18 years. Because no dosing or adverse event data are currently available on the use of neratinib in combination with DS-8201a in patients < 18 years of age, children are excluded from this study
  • Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Hemoglobin >= 9.0 g/dL (>= 8.0 g/dL for gastric cancer [GC] only) (within 14 days of enrollment)
  • No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
  • Leukocytes >= 3.0 K/cumm (within 14 days of enrollment)
  • Absolute neutrophil count >= 1.5 K/cumm (within 14 days of enrollment)
  • No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1 week prior to screening assessment
  • Platelets >= 100 K/cumm (within 14 days of enrollment)
  • No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
  • Serum albumin >= 2.5 g/dL (within 14 days of enrollment)
  • Total bilirubin =< 1.5 × institutional upper limit of normal (ULN), (< 3 × ULN in the presence of documented Gilbert's syndrome or liver metastases at baseline) (within 14 days of enrollment)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN (if liver metastases are present =< 5 x ULN) (within 14 days of enrollment)
  • International normalized ratio (INR)/prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< 1.5 x institutional ULN (within 14 days of enrollment)
  • This applies only to patients who are not receiving therapeutic anticoagulation that may affect INR. Those who are on therapeutic anticoagulation, should be on a stable dose for 4 weeks and should be considered within therapeutic range
  • Creatinine =< 1.5 x institutional ULN OR Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2 (using the Cockcroft-Gault equation) (within 14 days of enrollment)
  • 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 CHEMOTHERAPY-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 7 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 the following criteria are met: 1) follow-up brain imaging done at least in 4 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression and 2) the patient no longer requires steroids, or is on a stable steroid dose > 4 weeks
  • Patients with radiographically new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible only if has no progressive clinical symptoms and if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
  • Patients should be New York Heart Association functional classification of class 2B or better
  • Patients must have left ventricular ejection fraction (LVEF) >= 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization/enrollment
  • Part 2, Pancreatic cohort ONLY: Patients must have disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
  • Part 2, PD cohort ONLY: Patients must have disease that is evaluable or measurable by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • Part 2, PD cohort ONLY: Patients must have at least one lesion suitable for biopsy without significant risk to the patient. The biopsiable lesion can be the same as the evaluable lesion for response by RECIST 1.1
  • HER2 antibody conjugated to a topoisomerase 1 inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic; thus, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 1 month after the last dose of neratinib, or at least 7 months after the last dose of DS-8201a, whichever is longer (women of childbearing potential [WOCBP] only). 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 3 months after the last dose of neratinib, or 4 months after completion of DS-8021a administration, whichever is longer
  • 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
  • Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to enrollment in this study
  • Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration
  • Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member available will also be eligible

Who cannot join

  • With the exception of medications that are under investigation in the study (e.g., standard of care, comparators, or combination therapies), the following medications, treatment, and procedures will be prohibited during the treatment period:
  • Other anticancer therapy, including small-molecule targeted agents within 2 weeks or five half-lives, whichever is longer; chemotherapy otherwise not specified (including, but not limited to cytotoxic chemotherapy, antibody drug conjugates, retinoid therapy, hormonal therapy) within 3 weeks; immunotherapy or monoclonal antibody within 4 weeks; and nitrosoureas or mitomycin C within 6 weeks (concurrent use of hormones for noncancer-related conditions [e.g., insulin for diabetes and hormone replacement therapy] is acceptable)
  • Other investigational therapeutic agents
  • Patients who have had major surgery or radiation within 4 weeks; palliative stereotactic radiation within 2 weeks (except for palliative radiation to known metastatic sites as long as it does not affect assessment of response or interrupt treatment for more than the maximum time specified in dose modification section)
  • Radiotherapy to the thorax (palliative radiation to known metastatic sites in the thoracic spine is permitted in this study)
  • Concomitant use of chronic systemic (IV or oral) corticosteroids or other immunosuppressive medications except for managing adverse events (inhaled steroids or intra-articular steroid injections are permitted in this study); chronic replacement dose steroids (e.g., for those with adrenal insufficiency) are permitted in this study
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  • Subjects with bronchopulmonary disorders who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study
  • Concomitant treatment with chloroquine or hydroxychloroquine is not allowed during the study treatment due to concern for overlapping toxicities. If treatment with chloroquine and hydroxychloroquine treatment is absolutely required, study treatment must be interrupted. If chloroquine or hydroxychloroquine is administered, then a wash-out period of more than 14 days is required before restarting study treatment
  • Receipt of live, attenuated vaccine (messenger ribonucleic acid [mRNA] and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of study drug
  • Patients with 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
  • Patients with 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), 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 with history of allergic reactions attributed to compounds of similar chemical or biologic composition to DS-8201a, the inactive ingredients in the drug product, or neratinib
  • Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies
  • Patients receiving any medications or substances that are moderate or strong inhibitors or inducers of CYP3A4 and P-glycoprotein are ineligible. Avoid concomitant use with proton pump inhibitors and P-glycoprotein substrates. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Patients with a medical history of myocardial infarction within 6 months before enrollment, or symptomatic congestive heart failure (CHF) (New York Heart Association class II to IV)
  • Patients with a corrected QT interval (QTc) prolongation to > 470 ms (females) or > 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG)
  • Patients with clinically significant corneal disease in the opinion of the investigator
  • Patients with a pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART). (Drainage and CART are not allowed within 2 weeks prior to screening assessment) (GC indication)
  • Patients with spinal cord compression
  • 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 may be eligible per the discretion of the investigator after consultation with the sponsor medical monitor or designee (e.g., grade 2 chemotherapy-induced neuropathy)
  • Patients with 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 subject's participation in the clinical study or evaluation of the clinical study results
  • 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. These potential risks may also apply to other agents used in this study
  • Prior treatment with neratinib or DS-8201a
  • Clinically significant chronic gastrointestinal disorder with diarrhea as a major symptom; grade 2 (G2) or greater diarrhea at baseline. Please contact the study principal investigator (PI) for any patient with more than two episodes of diarrhea per day averaged over at least a 7 day period at time of screening to determine whether the diarrhea would be considered clinically significant
  • Inability to swallow tablets
  • Patients with active additional malignancy or a personal history of additional malignancy that may affect outcome of disease under treatment (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 at the discretion of the treating investigator are allowed)
  • Patients with prior allogeneic organ transplantation including allogeneic stem cell transplantation

Trial locations and contacts

18 sites in 1 country. Contact the study team or a site near you to ask about taking part.

18 sites in 1 country

United States18 sites, 15 recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

    Site Public Contact, 877-442-3324

    Geoffrey I. Shapiro

    Recruiting

  • Northwestern University

    Chicago, Illinois, 60611

    Site Public Contact, 312-695-1301, cancer@northwestern.edu

    Aparna Kalyan

    Recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    Site Public Contact, 800-293-5066, Jamesline@osumc.edu

    Floor Backes

    Recruiting

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

    Site Public Contact, 800-826-4673, becomingapatient@coh.org

    Dani R. Castillo

    Recruiting

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

    Site Public Contact, 352-273-8010

    Thomas J. George

    Recruiting

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

    Site Public Contact, 866-632-6789, askmdanderson@mdanderson.org

    Ecaterina E. Ileana Dumbrava

    Recruiting

  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

    Irvine, California, 92612

    Site Public Contact, 877-827-8839, ucstudy@uci.edu

    Farshid Dayyani

    Recruiting

  • City of Hope at Irvine Lennar

    Irvine, California, 92618

    Site Public Contact, 877-467-3411

    Dani R. Castillo

    Recruiting

  • City of Hope Antelope Valley

    Lancaster, California, 93534

    Suspended

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

    Site Public Contact, 859-257-3379

    Reema A. Patel

    Recruiting

  • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

    Madison, Wisconsin, 53718

    Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu

    Nataliya V. Uboha

    Recruiting

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

    Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu

    Nataliya V. Uboha

    Recruiting

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

    Site Public Contact, 877-827-8839, ucstudy@uci.edu

    Farshid Dayyani

    Recruiting

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

    Site Public Contact, 412-647-8073

    Sarah E. Taylor

    Recruiting

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

    Site Public Contact, 916-734-3089

    Mili Arora

    Recruiting

  • City of Hope South Pasadena

    South Pasadena, California, 91030

    Suspended

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Site Public Contact, 800-600-3606, info@siteman.wustl.edu

    Andrew Davis

    Recruiting

  • City of Hope Upland

    Upland, California, 91786

    Suspended

Other trials in United States

About this study

Official title: Phase I Trial of DS-8201a (Trastuzumab Deruxtecan) in Combination With Neratinib in Solid Tumors With HER2 Alterations

This phase I trial tests the safety, side effects, and best dose of neratinib in combination with trastuzumab deruxtecan in treating patients with solid tumors that have spread from where it first started (primary site) to other places in the body (metastatic) or that cannot be removed by surgery (unresectable), and have changes in a gene called human epidermal growth factor receptor 2 (HER2). Neratinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Adding neratinib to trastuzumab deruxtecan may be able to shrink cancer with a change in the HER2 gene.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess dose limiting toxicities and determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of neratinib maleate (neratinib) and trastuzumab deruxtecan (DS-8201a) in patients with advanced solid tumors harboring alterations in HER2 (including HER2 overexpression/amplification and selected HER2-activating mutations).

II. To evaluate the objective response rate (ORR) in patients with advanced pancreas cancer with HER2 activating mutations, amplification, and/or HER2 overexpression. (Part 2, Pancreatic Cohort ONLY)

SECONDARY OBJECTIVES:

  1. To observe and record anti-tumor activity of neratinib and DS-8201a, as measured by objective response rate (ORR), duration of response (DoR), and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by investigator assessment, and overall survival (OS).

II. To assess the safety and tolerability for the combination neratinib and DS-8201a.

III. To assess the effect of neratinib on DS-8201a payload (DXd/MAAA-1181a) tissue concentration in Part 2 pharmacodynamic (PD) Cohort at the RP2D chosen in part 1 (and potentially at a lower dose[s] of neratinib) before and after addition of neratinib to DS-8201a.

IV. To assess the pharmacokinetics of DS-8201a and neratinib in combination.

EXPLORATORY OBJECTIVES:

  1. To assess the pharmacodynamic response to neratinib and DS-8201a as measured by markers of DS-8201a-induced deoxyribonucleic acid (DNA) damage using gammaH2AX, phosphorylated (p) NBS1 and pKAP1 immunofluorescence assay (IFA), multiplex multiple reaction monitoring mass spectrometry (MRM)- based proteomic assay panel of DNA repair response pathway biomarkers, induction of apoptosis, and HER2 signaling along with other PD biomarkers such as cleaved caspase3 (apoptosis) and TOP1CC (target engagement) pending National Clinical Laboratory Network (NCLN) assay availability. (Part 1 Dose Escalation and Part 2 PD Cohorts) II. To assess quantifiable HER2 protein expression of pre-treatment or archival tumor biopsies, and at disease progression in correlation with treatment response.

III. To assess tumor tissue mutation profile pre-treatment and at progression in correlation with treatment response.

IV. To assess circulating cell-free DNA (cfDNA) mutation profiles pre-treatment, cycle 2 day 1 (C2D1), and at progression in correlation with treatment response.

OUTLINE: This is a dose-escalation study of neratinib followed by a dose-expansion (PD and Pancreatic Cohorts) study.

Patients receive neratinib orally (PO) once daily (QD) on days 1-21 of each cycle (days 8-21 of cycle 1, then days 1-21 in cycles thereafter for PD cohort) and trastuzumab deruxtecan intravenously (IV) over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, computed tomography (CT) scan and echocardiography or multigated acquisition (MUGA) scan throughout study. Additionally, patients may undergo a tissue biopsy at baseline if no archival sample available (dose-escalation cohort only), optionally at baseline (pancreatic cohort only), on study (PD cohort only), and optionally at disease progression (all cohorts).

After completion of study treatment, patients are followed up every 3 months for at least one year or until death.

Being tested
Biopsy Procedure, Biospecimen Collection, Computed Tomography, Echocardiography Test, Multigated Acquisition Scan
Medical subject headings
Neoplasm Metastasis, Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo echocardiography

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA scan

  • Neratinib MaleateDrug

    Also called 2-Butenamide, N-(4-((3-chloro-4-(2-pyridinylmethoxy)phenyl)amino)-3-cyano-7-ethoxy-6-quinolinyl)-4-(dimethylamino)-, (2E)-, (2Z)-2-butenedioate (1:1), HKI-272 Maleate, NERATINIB MALEATE ANHYDROUS, Nerlynx

    Given PO

  • Trastuzumab DeruxtecanBiological

    Also called DS-8201, DS-8201a, Enhertu, Fam-trastuzumab Deruxtecan-nxki

    Given IV

Study groups in NCT05372614
Study groupRoleWhat they receive
Treatment (neratinib, trastuzumab deruxtecan)ExperimentalPatients receive neratinib PO QD on days 1-21 of each cycle (days 8-21 of cycle 1, then days 1-21 in cycles thereafter for PD cohort) and trastuzumab deruxtecan IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, CT scan and echocardiography or MUGA scan throughout study. Additionally, patients may undergo a tissue biopsy at baseline if no archival sample available (dose-escalation cohort only), optionally at baseline (pancreatic cohort only), on study (PD cohort only), and optionally at disease progression (all cohorts).
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Drug: Neratinib Maleate; Biological: Trastuzumab Deruxtecan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose limiting toxicities (Part 1, Dose Escalation)

    Safety endpoints will be listed for each dose level.

    Measured: In the first 2 cycles in dose escalation of combination of neratinib and trastuzumab deruxtecan (DS-8201a) (cycle length = 21 days)

  2. Incidence of treatment-emergent adverse events (Part 1, Dose Escalation)

    Safety endpoints will be listed for each dose level and the tabulations of adverse events will also be produced by severity and by relationship to study drug.

    Measured: In the first 2 cycles of combination of neratinib and DS-8201a (cycle length = 21 days)

  3. Objective response rate (ORR) (Part 2, Pancreatic Cohort)

    ORR will be determined as the proportion of subjects with a confirmed partial response (PR) or complete response (CR). The ORR and 90% confidence intervals (CIs) will be constructed using the Clopper-Pearson method for ORR to form repeated CIs according to Jennison and Turnbull at the interim analysis and primary analysis, respectively. The nominal p-value from the exact binomial test will also be reported.

    Measured: Up to 1 year

Secondary outcomes (8)

  1. Incidence of adverse events

    Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 1 year

  2. Objective response rate

    Defined as the percentage of patients who achieve CR or PR per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.

    Measured: Up to 1 year

  3. Duration of response (Pancreatic Expansion Cohort)

    By RECIST v 1.1. Summary statistics of DOR will be calculated for responders.

    Measured: Time from first documentation of response (CR or PR) until the time of first documentation of disease progression, assessed up to 1 year

  4. Progression free survival (Pancreatic Expansion Cohort)

    By RECIST v 1.1. Described using Kaplan-Meier product limit methods.

    Measured: Time from first dose to the earlier date of assessment of progression or death by any cause in the absence of progression, assessed up to 1 year

  5. Overall survival (Pancreatic Expansion Cohort)

    Described using Kaplan-Meier product limit methods.

    Measured: From date of first dose to the date of death by any cause, assessed up to 1 year

  6. DXd (MAAA-1181a) tissue concentration (Pharmacodynamic [PD] Expansion Cohort)

    Summarized using descriptive statistics (means, median, and standard deviations) at each measurement time point and the change will be compared by paired t-test or Wilcoxon rank-sum test as appropriate.

    Measured: Up to 1 year

  7. Pharmacokinetic (PK) profiles of DS-8201a and its metabolites (PD Expansion Cohort)

    PK will be analyzed using descriptive statistics. Analysis of variance (ANOVA) and regression model may be used to investigate any possible relationship of PK biomarker levels with anti-tumor efficacy. Endpoint data will be analyzed, reporting the mean, standard deviation, median, minimum, and maximum values.

    Measured: Up to 1 year

  8. PK profiles of neratinib and its metabolites (PD Expansion Cohort)

    PK will be analyzed using descriptive statistics. ANOVA and regression model may be used to investigate any possible relationship of PK biomarker levels with anti-tumor efficacy. Endpoint data will be analyzed, reporting the mean, standard deviation, median, minimum, and maximum values.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 May 2022
  2. Study start5 Oct 2022
  3. Primary completion17 Jul 2028 (estimated)
  4. Study completion17 Jul 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
58 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05372614
Sponsor's protocol ID
NCI-2022-04099
Other IDs
NCI-2022-04099, 202207020, 10495, 10495, UM1CA186689
Status last verified
Sep 2026
First submitted
12 May 2022
Last updated
2 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: "NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."

Publications

  • Jhaveri K, Eli LD, Wildiers H, Hurvitz SA, Guerrero-Zotano A, Unni N, Brufsky A, Park H, Waisman J, Yang ES, Spanggaard I, Reid S, Burkard ME, Vinayak S, Prat A, Arnedos M, Bidard FC, Loi S, Crown J, Bhave M, Piha-Paul SA, Suga JM, Chia S, Saura C, Garcia-Saenz JA, Gambardella V, de Miguel MJ, Gal-Yam EN, Rapael A, Stemmer SM, Ma C, Hanker AB, Ye D, Goldman JW, Bose R, Peterson L, Bell JSK, Frazier A, DiPrimeo D, Wong A, Arteaga CL, Solit DB. Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial. Ann Oncol. 2023 Oct;34(10):885-898. doi: 10.1016/j.annonc.2023.08.003. Epub 2023 Aug 18.

    PubMed 37597578

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Metastatic Malignant Solid Neoplasm and Metastatic Pancreatic Adenocarcinoma, run by National Cancer Institute (NCI) at 18 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 78 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose limiting toxicities (Part 1, Dose Escalation) (time frame: In the first 2 cycles in dose escalation of combination of neratinib and trastuzumab deruxtecan (DS-8201a) (cycle length = 21 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05372614, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.

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