Trastuzumab Deruxtecan + Neratinib for Cancer

Recruiting in Palo Alto (17 mi)

+18 other locations

Overseen ByHaeseong Park

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, P-glycoprotein inducers

Disqualifiers: Interstitial lung disease, Severe COPD, Myocardial infarction, others

No Placebo Group

Trial Summary

What is the purpose of this trial?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.

Eligibility Criteria

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.

Inclusion Criteria

I have a tumor that can be safely biopsied.

I have recovered from serious side effects of my previous cancer treatment.

I am 18 years old or older.

I have chronic hepatitis B but my viral load is undetectable.

My heart condition allows me to perform daily activities with slight limitations.

I am HIV-positive but stable on my medication and healthy.

My tumor is HER2 positive based on specific tests.

My kidney function is within the required range.

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.

Exclusion Criteria

I have another type of cancer that could affect my current treatment.

I am not taking any medications that could interfere with the trial.

I have previously been treated with neratinib or DS-8201a.

I have a long-term stomach problem that mainly causes diarrhea.

I cannot swallow pills.

Participant Groups

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.

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.