What side effects are associated with this type of intervention?

Common treatments for stomach cancer, particularly those involving Tyrosine Kinase Inhibitors (TKIs) like Neratinib and Antibody-Drug Conjugates (ADCs) like TDxD, have several known side effects. TKIs often cause diarrhea, nausea, vomiting, fatigue, and liver toxicity. ADCs can lead to decreased neutrophil count, anemia, nausea, and interstitial lung disease, which can be severe and potentially fatal. These side effects are important considerations for patients and healthcare providers when planning treatment.

What prior FDA approvals exist?

For the treatment of stomach cancer, particularly HER2-positive gastric adenocarcinoma, the FDA has approved several targeted therapies. Trastuzumab, a monoclonal antibody targeting HER2, was one of the first approved treatments for HER2-positive gastric cancer. More recently, the FDA approved Fam-trastuzumab deruxtecan (TDxD), an antibody-drug conjugate targeting HER2, for patients with advanced HER2-positive gastric cancer who have received prior trastuzumab-based therapy. These treatments are similar to the investigational combination of Neratinib, a Tyrosine Kinase Inhibitor targeting HER2, and TDxD, which is currently being studied for its efficacy and safety in this patient population.

What other types of research exist?

Promising alternatives to Neratinib plus TDxD for HER2-positive stomach cancer patients include: 1) Trastuzumab combined with chemotherapy, which remains a standard first-line treatment. 2) Pembrolizumab, an immune checkpoint inhibitor, especially for patients with high PD-L1 expression. 3) Ramucirumab plus paclitaxel, which has shown efficacy in second-line treatment. 4) Ado-trastuzumab emtansine (T-DM1), which is an alternative for patients who have progressed on trastuzumab and chemotherapy.

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Antibody-Drug Conjugate

Neratinib + TDxD for Esophageal and Stomach Cancer

Phase 1

Recruiting

Led By Namrata Vijavergia, MD

Research Sponsored by Namrata Vijayvergia

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs, Neratinib and TDxD, in patients with advanced stomach cancer that overexpresses HER2. These patients have not responded to previous treatments. The drugs work by blocking cancer growth and directly killing cancer cells.

Who is the study for?

This trial is for adults over 18 with advanced gastro-esophageal cancer that's HER2-overexpressing and has worsened despite previous chemotherapy and HER2 therapy. Participants need good blood counts, organ function, no severe heart issues or uncontrolled illnesses, not pregnant or breastfeeding, willing to use contraception, and able to take oral meds.

What is being tested?

The study tests the combination of Neratinib (a pill) with Fam-Trastuzumab Deruxtecan-Nxki (TDxD) in a Phase 1 trial to find safe dosages. It uses a '3+3' method where small groups are given increasing doses until the maximum tolerated dose is found for patients who've had prior treatments fail.

What are the potential side effects?

Potential side effects include reactions related to liver function changes, diarrhea, potential heart problems as indicated by ejection fraction requirements in eligibility criteria, possible blood count abnormalities due to marrow suppression risk factors mentioned in exclusion criteria.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of the combination of TDxD and Neratinib

Secondary study objectives

Determine the Disease Control Rate (DCR) (CR + PR + Stable Disease (SD)) of the combination of TDxD and Neratinib

Determine the Objective Response Rate (ORR) (Complete Response (CR) + Partial Response (PR)) of the combination of TDxD and Neratinib

Determine the Overall Survival (OS) of the combination of TDxD and Neratinib

+1 more

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: Neratinib plus TDxDExperimental Treatment2 Interventions

Neratinib oral daily days 1-21 plus TDxD on day 1 administered intravenously of a 21 day treatment cycle.

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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

The most common treatments for stomach cancer, particularly those targeting HER2, include tyrosine kinase inhibitors (TKIs) like Neratinib and antibody-drug conjugates (ADCs) like fam-trastuzumab deruxtecan (TDxD). Neratinib works by inhibiting the HER2 receptor's kinase activity, which is essential for the growth and survival of cancer cells. TDxD combines an anti-HER2 antibody with a cytotoxic drug, delivering the drug directly to HER2-expressing cancer cells, thereby enhancing its efficacy while minimizing systemic toxicity. These targeted therapies are significant for stomach cancer patients as they offer a more precise treatment approach, potentially improving survival rates and reducing side effects compared to traditional chemotherapy.

Trastuzumab-deruxtecan: an investigational agent for the treatment of HER2-positive breast cancer.New drugs for breast cancer.