Trastuzumab Deruxtecan + Neratinib for Cancer

Recruiting at19 trial locations

Overseen by Andrew A Davis

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.

Research Team

Andrew A Davis

Principal Investigator

Yale University Cancer Center LAO

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

Absolute neutrophil count >= 1.5 K/cumm

I have a tumor that can be safely biopsied.

Platelets >= 100 K/cumm

Exclusion Criteria

Pregnant or breastfeeding women

Patients with prior allogeneic organ transplantation including allogeneic stem cell transplantation

Patients receiving prohibited medications, treatments, or procedures during the treatment period

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Patients receive neratinib and trastuzumab deruxtecan to assess dose limiting toxicities and determine the maximum tolerated dose

6 weeks

3 visits (in-person)

Dose Expansion

Patients continue to receive neratinib and trastuzumab deruxtecan at the recommended phase 2 dose to observe anti-tumor activity

Up to 1 year

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Every 3 months (in-person)

Treatment Details

Interventions

• Neratinib Maleate (Kinase Inhibitor)
• Trastuzumab Deruxtecan (Monoclonal Antibodies)

Trial Overview 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.

Participant Groups

Group I: Treatment (neratinib, trastuzumab deruxtecan) Experimental Treatment 7 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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School