Trastuzumab Deruxtecan + Nivolumab for Esophageal Cancer

Recruiting at 1 trial location

Overseen By Brown University Oncology Research Group

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brown University

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Substance abuse, Cardiac conditions, Autoimmune disorders, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 17

Duration: 12 months

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination treatment for individuals with esophageal cancer exhibiting high levels of the protein HER2. Researchers aim to determine if adding trastuzumab deruxtecan, a cancer drug, to nivolumab (also known as Opdivo, an immune therapy), is safe and effective following standard treatments like surgery and chemoradiation. Participants should have undergone surgery for esophageal cancer with specific HER2 characteristics and completed prior treatments without complete cancer elimination. The trial will explore different dosages of trastuzumab deruxtecan to find the optimal balance of safety and effectiveness. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that patients should not have unresolved toxicities from previous anticancer therapy and should not be on systemic corticosteroids or other immunosuppressive medications within 14 days of starting the study drugs. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that trastuzumab deruxtecan is usually well-tolerated. Studies have found that this treatment has a manageable safety profile. In trials, many patients experienced positive results with few serious side effects. Common but mild side effects include nausea and tiredness, while serious side effects are less common. This drug is already used for other types of cancer, suggesting it is considered safe for wider use.

For the combination with nivolumab, previous studies on nivolumab alone show it is also usually well-tolerated. Common side effects include tiredness and skin rash, with serious side effects being rare but possible.

Overall, past research has shown that both trastuzumab deruxtecan and nivolumab are generally safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Trastuzumab deruxtecan is unique because it combines a targeted therapy with chemotherapy in a single molecule. Unlike traditional treatments for esophageal cancer, which often involve separate chemotherapy and targeted therapy regimens, this drug directly delivers chemotherapy to cancer cells by attaching it to an antibody that targets HER2, a protein often overexpressed in these cancers. This targeted approach could lead to more effective treatment with potentially fewer side effects. Researchers are excited because it represents a more precise method of attacking cancer cells while sparing healthy ones, potentially improving outcomes for patients.

What evidence suggests that this trial's treatments could be effective for esophageal cancer?

Research shows that trastuzumab deruxtecan holds promise for treating HER2-positive cancers, such as those in the stomach and esophagus. Studies have found that patients using trastuzumab deruxtecan responded better and lived longer than those on standard treatments. Specifically, one study demonstrated that it helped patients with advanced cancer live longer. This treatment targets the HER2 protein, often abundant in these cancers, and delivers a potent drug to kill the cancer cells. These findings suggest that trastuzumab deruxtecan could be a viable option for people with HER2-positive esophageal cancer. This trial tests different dosages of trastuzumab deruxtecan to determine the most effective and safe dose for participants. ^{3 4 5 6 7}

Who Is on the Research Team?

Howard Safran, MD

Principal Investigator

Lifespan Cancer Institute

Manish A Shah, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for adults who've had surgery after chemoradiation for HER2+ esophageal or gastroesophageal junction cancer but didn't have a complete response. They must be 4-12 weeks post-surgery, with certain stages of disease pre-treatment, and agree to contraception if applicable. Excluded are those previously treated with similar drugs, having significant heart issues, other cancers within 3 years (some exceptions), uncontrolled infections, or severe allergies to study drugs.

Inclusion Criteria

I am a man who can father children and will use a condom with spermicide.

My cancer shows high levels of HER2.

I will not donate eggs or breastfeed from enrollment until 7 months after my last treatment.

Exclusion Criteria

I am not planning to receive other cancer treatments not specified by this trial.

I have not received a live vaccine in the last 30 days.

Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions that may interfere with the subject's participation in the clinical study or evaluation of the clinical study results

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive trastuzumab deruxtecan and nivolumab every 21 days for 17 doses over 1 year

12 months

17 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

Long-term follow-up

Participants are monitored for disease-free survival and recurrence

up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Trastuzumab deruxtecan

Trial Overview The trial tests the safety and effectiveness of Trastuzumab Deruxtecan (Enhertu) combined with Nivolumab in patients who are disease-free post-trimodality treatment for HER2+ esophagogastric cancer. It's an open-label phase II study where all participants receive the drug combination for one year.

How Is the Trial Designed?

Group I: Starting Trastuzumab Deruxtecan Dose Experimental Treatment 2 Interventions

Trastuzumab deruxtecan, 6.4 mg/kg IV every 3 weeks for 17 doses (12 months)

Group II: Second Trastuzumab Deruxtecan Dose Reduction Experimental Treatment 2 Interventions

Trastuzumab deruxtecan, 4.4 mg/kg IV every 3 weeks for 17 doses (12 months)

Group III: First Trastuzumab Deruxtecan Dose Reduction Experimental Treatment 2 Interventions

Trastuzumab deruxtecan, 5.4 mg/kg IV every 3 weeks for 17 doses (12 months)

Trastuzumab deruxtecan is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Enhertu for:

• Unresectable or metastatic HER2-positive breast cancer
• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma
• Unresectable or metastatic HER2-low breast cancer
• Unresectable or metastatic HER2-positive solid tumors

Approved in European Union as Enhertu for:

• Unresectable or metastatic HER2-positive breast cancer
• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma

Approved in Japan as Enhertu for:

• Unresectable or metastatic HER2-positive breast cancer
• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma

Who Is Running the Clinical Trial?

Brown University

Lead Sponsor

Trials

480

Recruited

724,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In the DESTINY-Gastric02 trial involving 79 patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer, trastuzumab deruxtecan demonstrated a confirmed objective response rate of 42% after a median follow-up of 10.2 months, indicating its efficacy as a second-line therapy.

While trastuzumab deruxtecan showed promising results, it was associated with some serious adverse events, including two treatment-related deaths due to interstitial lung disease or pneumonitis, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02): primary and updated analyses from a single-arm, phase 2 study. Van Cutsem, E., di Bartolomeo, M., Smyth, E., et al.[2023]

In a phase 2 trial involving 187 patients with HER2-positive advanced gastric cancer, trastuzumab deruxtecan showed a significantly higher objective response rate of 51% compared to 14% for standard chemotherapy, indicating its superior efficacy.

Patients treated with trastuzumab deruxtecan also experienced longer overall survival (median 12.5 months) compared to those receiving chemotherapy (median 8.4 months), although notable side effects included myelosuppression and interstitial lung disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. Shitara, K., Bang, YJ., Iwasa, S., et al.[2021]

Trastuzumab deruxtecan significantly improves response rates and overall survival in patients with HER2-positive metastatic gastroesophageal carcinoma, marking a breakthrough in treatment options.

This immunoconjugate represents a major advancement, as previous HER2-targeted therapies, aside from trastuzumab, have not demonstrated substantial benefits for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breaking Barriers in HER2+ Cancers. Siena, S., Marsoni, S., Sartore-Bianchi, A.[2021]

Trastuzumab deruxtecan (T-DXd) demonstrated clinical activity in patients with HER2-low gastric or gastroesophageal junction adenocarcinoma, showing a confirmed objective response rate of 26.3% in cohort 1 and 9.5% in cohort 2, with many patients experiencing reduced tumor size.

The treatment was generally well-tolerated, with no drug-related deaths reported, although some patients experienced significant adverse events like anemia and decreased neutrophil counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Anti-Human Epidermal Growth Factor Receptor 2 Treatment-Naive Patients With Human Epidermal Growth Factor Receptor 2-Low Gastric or Gastroesophageal Junction Adenocarcinoma: Exploratory Cohort Results in a Phase II Trial. Yamaguchi, K., Bang, YJ., Iwasa, S., et al.[2023]

Trastuzumab deruxtecan (ENHERTU®) is an innovative treatment that combines an antibody targeting HER2 with a DNA topoisomerase I inhibitor, specifically designed for HER2-expressing solid tumors, including various types of cancer.

It received accelerated approval in the USA based on the promising results from the phase 2 DESTINY-Breast01 trial, which focused on patients with advanced HER2-positive breast cancer who had already undergone multiple treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: First Approval. Keam, SJ.[2020]

Trastuzumab deruxtecan (Enhertu®) has been shown to significantly improve progression-free survival in adults with unresectable or metastatic HER2-positive breast cancer compared to the previous standard treatment, trastuzumab emtansine, in a pivotal phase 3 trial.

The treatment has a generally manageable safety profile, although it is associated with common adverse events like hematological and gastrointestinal disorders, and requires careful monitoring for interstitial lung disease (ILD)/pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer. Nie, T., Blair, HA.[2023]

Trastuzumab deruxtecan (Enhertu®) has been shown to be significantly more effective than standard chemotherapy in improving overall survival and achieving objective responses in adults with advanced HER2-positive gastric or gastro-oesophageal junction adenocarcinoma, based on results from the phase II DESTINY-Gastric01 trial.

The treatment is generally well-tolerated, with common side effects including nausea and fatigue, but it does carry important safety warnings for interstitial lung disease and embryo-foetal toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Gastric or Gastro-Oesophageal Junction Adenocarcinoma. Kang, C.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11298287/

Trastuzumab deruxtecan in Western patients with HER2 ... The objective of this study was to assess the activity and safety of T-DXd monotherapy in Western patients with metastatic and/or unresectable ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2004413

Trastuzumab Deruxtecan in Previously Treated HER2- ... Therapy with trastuzumab deruxtecan led to significant improvements in response and overall survival, as compared with standard therapies, among patients with ...

3. enhertuhcp.com enhertuhcp.com/en/gastric/efficacy/efficacy-data

Efficacy Data | ENHERTU® (fam-trastuzumab deruxtecan-nxki) Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.242

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with ... In the primary analysis (101 OS events; median survival follow-up, 12.3 mo), T-DXd showed statistically significant benefit vs standard ...

5. daiichisankyo.com daiichisankyo.com/files/news/pressrelease/pdf/202503/20250303_E.pdf

"ENHERTU® (Trastuzumab Deruxtecan) DESTINY- ... “The results of DESTINY-Gastric04 show that second-line treatment with ENHERTU can extend survival compared with a chemotherapy-based regimen ...

6. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/ENHERTU-fam-trastuzumab-deruxtecan-nxki-reduced-the-risk-of-disease-recurrence-or-death-by-53-percent-vs-T-DM1-in-patients-with-high-risk-HER2-positive-early-breast-cancer-following-neoadjuvant-therapy-in-DESTINY-Breast05-Phase-III-trial.html

ENHERTU® (fam-trastuzumab deruxtecan-nxki) reduced ... More than 92% of patients treated with AstraZeneca and Daiichi Sankyo's ENHERTU were free of invasive disease at three years.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9901967/

Trastuzumab Deruxtecan in Anti–Human Epidermal Growth ... To investigate efficacy and safety of trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2 (HER2)–low gastric or gastroesophageal ...