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Kinase Inhibitor
Trastuzumab Deruxtecan + Neratinib for Cancer
Phase 1
Waitlist Available
Led By Andrew A Davis
Research Sponsored by National Cancer Institute (NCI)
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial Must have
Patients must have at least one lesion suitable for biopsy without significant risk to the patient
Patients who had clinically significant side effects from prior cancer therapy must have recovered to grade 1 or below
Must not have
Patients with active additional malignancy or a personal history of additional malignancy that may affect outcome of disease under treatment
Concomitant use of certain medications or substances
Timeline
Screening 3 weeks
Treatment Varies
Follow Up up to 1 year
Awards & highlights
No Placebo-Only Group
Summary
This trial tests the safety and best dose of combining neratinib and trastuzumab deruxtecan for patients with advanced HER2-positive tumors. Neratinib stops cancer cell growth, and trastuzumab deruxtecan delivers chemotherapy directly to the cancer cells. The goal is to find the best dose and see how well this combination works. Neratinib has been shown to overcome trastuzumab resistance in HER2-positive breast cancer.
Who is the study for?
Adults with advanced solid tumors that can't be removed by surgery or have spread, and have changes in the HER2 gene. They must not have had previous treatments with neratinib or DS-8201a, should not be pregnant or breastfeeding, and need to agree to use contraception. People with certain heart conditions, severe lung issues, recent major surgeries or radiation therapy are excluded.
What is being tested?
The trial is testing the combination of two anti-cancer drugs: Trastuzumab Deruxtecan and Neratinib Maleate for safety and optimal dosing against cancers with HER2 gene alterations. It includes various assessments like scans and biopsies to monitor effects.
What are the potential side effects?
Potential side effects include reactions related to the immune system such as inflammation of organs (like lungs), digestive problems including diarrhea, blood disorders which could affect cell counts, fatigue from treatment-related anemia, possible heart complications due to drug interactions.
Eligibility Criteria
Inclusion Criteria
You may be eligible if you check “Yes” for the criteria belowSelect...
I have a tumor that can be safely biopsied.
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I have recovered from serious side effects of my previous cancer treatment.
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I am 18 years old or older.
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I have chronic hepatitis B but my viral load is undetectable.
Select...
My heart condition allows me to perform daily activities with slight limitations.
Select...
I am HIV-positive but stable on my medication and healthy.
Select...
My tumor is HER2 positive based on specific tests.
Select...
My kidney function is within the required range.
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I am mostly active and can carry out light work.
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My brain metastases have been treated.
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I have had at least one treatment for my cancer after it spread.
Exclusion Criteria
You may be eligible for the trial if you check “No” for criteria below:Select...
I have another type of cancer that could affect my current treatment.
Select...
I am not taking any medications that could interfere with the trial.
Select...
I have previously been treated with neratinib or DS-8201a.
Select...
I have a long-term stomach problem that mainly causes diarrhea.
Select...
I cannot swallow pills.
Timeline
Screening ~ 3 weeks3 visits
Treatment ~ Varies
Follow Up ~ up to 1 year
Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~up to 1 year
Treatment Details
Study Objectives
Study objectives can provide a clearer picture of what you can expect from a treatment.Primary study objectives
Incidence of dose limiting toxicities
Incidence of treatment-emergent adverse events
Secondary study objectives
DXd (MAAA-1181a) tissue concentration
Duration of response
Incidence of adverse events
+5 moreOther study objectives
Deoxyribonucleic acid (DNA) damage
Quantitative HER2 protein
Tumor mutation profile
Side effects data
From 2024 Phase 2 trial • 95 Patients • NCT0498981677%
Anaemia
73%
White blood cell count decreased
61%
Neutrophil count decreased
53%
Platelet count decreased
43%
Nausea
40%
Decreased appetite
39%
Hypoalbuminaemia
32%
Aspartate aminotransferase increased
32%
Vomiting
28%
Weight decreased
26%
Hypokalaemia
25%
Asthenia
25%
Alanine aminotransferase increased
24%
Hypocalcaemia
22%
Hyponatraemia
19%
Constipation
19%
Fatigue
17%
Lymphocyte count decreased
15%
Diarrhoea
13%
Covid-19
12%
Blood alkaline phosphatase increased
12%
Gamma-glutamyltransferase increased
12%
Blood bilirubin increased
9%
Hyperuricaemia
9%
Pyrexia
9%
Dizziness
8%
Hyperglycaemia
8%
Abdominal distension
7%
Oedema peripheral
7%
Insomnia
6%
Thrombocytopenia
6%
Bilirubin conjugated increased
6%
Blood creatinine increased
6%
White blood cell count increased
6%
Hypochloraemia
6%
Abdominal pain
6%
Dyspepsia
6%
Hypoaesthesia
5%
Coronavirus infection
5%
Cough
5%
Pneumonia
5%
Hepatic function abnormal
5%
Amylase increased
5%
Blood lactate dehydrogenase increased
5%
Ejection fraction decreased
5%
Hypoproteinaemia
5%
Back pain
5%
Mouth ulceration
5%
Interstitial lung disease
5%
Productive cough
4%
Covid-19 pneumonia
3%
Gastrointestinal haemorrhage
2%
Febrile neutropenia
2%
Death
1%
Cerebral infarction
1%
Myelosuppression
1%
Haemorrhage intracranial
1%
Dysphagia
1%
Jaundice cholestatic
1%
Gastrointestinal infection
1%
Malnutrition
1%
Mental disorder
1%
Haematuria
1%
Renal failure
1%
Pulmonary embolism
1%
Deep vein thrombosis
1%
Arrhythmia
1%
Sepsis
1%
Upper gastrointestinal haemorrhage
100%
80%
60%
40%
20%
0%
Study treatment Arm
T-DXd
Awards & Highlights
No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.
Trial Design
1Treatment groups
Experimental Treatment
Group I: Treatment (neratinib, trastuzumab deruxtecan)Experimental Treatment7 Interventions
Patients receive neratinib PO QD on days 1-21 (days 8-21 of cycle 1, then days 1-21 in cycles thereafter for PD study) of each cycle 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 echocardiograpahy or MUGA scan throughout study. Additionally, patients may undergo a tissue biopsy at baseline.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Biospecimen Collection
2004
Completed Phase 3
~2030
Echocardiography
2013
Completed Phase 4
~11580
Computed Tomography
2017
Completed Phase 2
~2790
Multigated Acquisition Scan
2015
Completed Phase 3
~270
Trastuzumab Deruxtecan
2021
Completed Phase 2
~100
Biopsy
2014
Completed Phase 4
~1150
Research Highlights
Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Kinase inhibitors, like Neratinib, block specific enzymes that signal cancer cells to grow, thereby slowing or stopping tumor growth. Antibody-drug conjugates, such as Trastuzumab Deruxtecan, combine a monoclonal antibody targeting cancer cells with a chemotherapy drug, delivering the drug directly to the cancer cells and minimizing damage to healthy cells.
These targeted treatments are crucial for cancer patients as they can be more effective and have fewer side effects compared to traditional chemotherapy.
Promising novel therapies for the treatment of endometrial cancer.New agents in advanced non-small-cell lung cancer treatment.New developments in the treatment of esophageal cancer.
Promising novel therapies for the treatment of endometrial cancer.New agents in advanced non-small-cell lung cancer treatment.New developments in the treatment of esophageal cancer.
Find a Location
Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
13,957 Previous Clinical Trials
41,112,057 Total Patients Enrolled
Andrew A DavisPrincipal InvestigatorYale University Cancer Center LAO
Haeseong ParkPrincipal InvestigatorYale University Cancer Center LAO
1 Previous Clinical Trials
Media Library
Eligibility Criteria:
This trial includes the following eligibility criteria:- I have a tumor that can be safely biopsied.I have recovered from serious side effects of my previous cancer treatment.I have not had major surgery or radiation recently.I am 18 years old or older.I have chronic hepatitis B but my viral load is undetectable.I have another type of cancer that could affect my current treatment.My heart condition allows me to perform daily activities with slight limitations.I am HIV-positive but stable on my medication and healthy.I am not taking any medications that could interfere with the trial.My tumor is HER2 positive based on specific tests.I have previously been treated with neratinib or DS-8201a.My kidney function is within the required range.I have a long-term stomach problem that mainly causes diarrhea.I cannot swallow pills.I am mostly active and can carry out light work.My brain metastases have been treated.I have had at least one treatment for my cancer after it spread.My cancer has spread or cannot be removed, and this trial is considered my best next treatment option.
Research Study Groups:
This trial has the following groups:- Group 1: Treatment (neratinib, trastuzumab deruxtecan)
Awards:
This trial has 1 awards, including:- No Placebo-Only Group - All patients enrolled in this study will receive some form of active treatment.
Timeline:
This trial has the following timeline:- Screening: It may take up to 3 Weeks to process to see if you qualify in this trial.
- Treatment: The duration you will receive the treatment varies.
- Follow Ups: You may be asked to continue sharing information regarding the trial for 6 Months after you stop receiving the treatment.