Pembrolizumab + Trastuzumab + Chemotherapy for Esophageal Cancer

Recruiting at 11 trial locations

Overseen By Yelena Janjigian, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Anti-PD-1, Anti-HER2, others

Disqualifiers: Metastatic disease, Immunodeficiency, Autoimmune disorders, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12-16 weeks

49 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study to find out whether adding trastuzumab and pembrolizumab to standard chemotherapy is an effective treatment for resectable HER2+ esophagogastric cancer.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it does mention that you cannot be on systemic steroid therapy or other immunosuppressive treatments within 7 days before starting the trial, unless it's a low dose or specific type like inhaled corticosteroids. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination of Pembrolizumab, Trastuzumab, and Chemotherapy for esophageal cancer?

Research shows that combining Pembrolizumab with Trastuzumab and chemotherapy can significantly reduce tumor size and improve response rates in patients with HER2-positive gastric or gastro-esophageal junction cancer, which is similar to esophageal cancer. Pembrolizumab has also been approved for use in esophageal cancer, indicating its potential effectiveness. ^{1 2 3 4 5}

Is the combination of Pembrolizumab, Trastuzumab, and Chemotherapy safe for humans?

Pembrolizumab and Trastuzumab have been used safely in humans for various cancers, including esophageal cancer, often in combination with chemotherapy. These treatments are generally considered safe, but like all cancer treatments, they can have side effects, which should be discussed with a healthcare provider. ^{1 2 3 5 6}

What makes the drug combination of pembrolizumab, trastuzumab, and chemotherapy unique for esophageal cancer?

This drug combination is unique because it combines pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with trastuzumab, a targeted therapy for HER2-positive cancers, and chemotherapy, potentially offering a more effective treatment for HER2-positive esophageal cancer compared to using these drugs individually. ^{1 5 7 8 9}

Research Team

Yelena Janjigian, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with HER2+ esophagogastric cancer who can potentially have their tumor completely removed by surgery. They must be in good physical condition (ECOG 0-1), agree to use contraception, and not be pregnant or breastfeeding. Their organs must function well enough to handle the treatments.

Inclusion Criteria

My esophageal or stomach cancer is HER2 positive.

My primary tumor can be completely removed by surgery.

I agree to use birth control and not donate sperm for 230 days after my last treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant pembrolizumab with trastuzumab and chemotherapy

12-16 weeks

Surgery

Participants undergo surgical resection of the tumor

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 18 months

Treatment Details

Interventions

• Pembrolizumab
• Trastuzumab

Trial Overview The study is testing if adding trastuzumab (a drug targeting HER2 proteins) and pembrolizumab (an immunotherapy drug) to standard chemotherapy improves outcomes for patients with resectable HER2+ esophagogastric cancer.

Participant Groups

Group I: Esophagogastric Cancer Experimental Treatment 6 Interventions

Participants will have a diagnosis of resectable HER2+ (IHC 3+ or IHC 2+/FISH ratio \>2.0) esophageal, GEJ or gastric cancer.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Trastuzumab, an anti-HER2 agent, is approved for first-line treatment in HER2 positive gastro-esophageal adenocarcinoma, showing effectiveness when combined with chemotherapy, but not with neoadjuvant chemoradiotherapy for advanced cases.

Immune checkpoint inhibitors like nivolumab and pembrolizumab have been approved for specific uses in esophageal cancer, and combining these with other therapies may enhance treatment outcomes, with ongoing clinical trials exploring these combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectivity of targeted therapy and immunotherapy in patients with advanced metastatic and non-metastatic cancer of the esophagus and esophago-gastric junction. Valkema, MJ., Mostert, B., Lagarde, SM., et al.[2023]

Biologic therapies, particularly those targeting HER2 and VEGF, are showing promise in treating esophageal and gastric cancers, with trastuzumab and ramucirumab currently recommended by the NCCN for specific patient groups.

Recent studies indicate that other agents like pertuzumab, apatinib, and pembrolizumab may improve overall and progression-free survival, suggesting a growing role for targeted biologic therapies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. Samson, P., Lockhart, AC.[2020]

Preoperative treatment with pembrolizumab combined with chemoradiotherapy was found to be safe for 20 patients with resectable esophageal squamous cell carcinoma, with a high pathologic complete response (pCR) rate of 55.6%.

Despite some patients experiencing significant adverse events, including grade III lymphopenia in 65% of cases, the treatment did not delay surgery, indicating its feasibility for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). Li, C., Zhao, S., Zheng, Y., et al.[2021]

In the KEYNOTE-811 study, combining pembrolizumab with trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma significantly reduced tumor size and improved the objective response rate, indicating enhanced efficacy of this treatment regimen.

The study highlights that this combination therapy not only induces complete responses in some patients but also represents a promising advancement in the treatment of unresectable or metastatic HER2-positive cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Janjigian, YY., Kawazoe, A., Yañez, P., et al.[2022]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a study of 55 patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC), pembrolizumab combined with chemotherapy or radiotherapy showed favorable long-term survival outcomes, with a 12-month overall survival rate of 78.8%.

The treatment was found to be safe and manageable, with long-term adverse effects reported in only a small number of patients, indicating that pembrolizumab is a promising option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and predictors of pembrolizumab-based regimens in patients with advanced esophageal cancer in the real world. Wang, HC., Huang, X., Chen, J., et al.[2023]

In a phase 2 trial involving 37 patients with HER2-positive metastatic oesophagogastric cancer, the combination of pembrolizumab, trastuzumab, and chemotherapy resulted in 70% of patients being progression-free at 6 months, indicating promising efficacy.

The treatment was generally safe, with the most common adverse effect being neuropathy in 97% of patients, but no treatment-related deaths were reported, suggesting a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab and trastuzumab in HER2-positive oesophageal, gastric, or gastro-oesophageal junction cancer: an open-label, single-arm, phase 2 trial. Janjigian, YY., Maron, SB., Chatila, WK., et al.[2021]

Nivolumab and pembrolizumab, both PD-1 inhibitors, have shown improved overall survival in patients with esophageal cancer, particularly in trials like ATTRACTION-3 and KEYNOTE-181, which involved patients with esophageal squamous cell carcinoma and those with high PD-L1 expression, respectively.

Ongoing trials are exploring the effectiveness of combining immune checkpoint inhibitors with traditional chemotherapy and radiotherapy, which may lead to better treatment options and outcomes for esophageal cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immuno-oncology for esophageal cancer. Yamamoto, S., Kato, K.[2021]

References

1. Italy pubmed.ncbi.nlm.nih.gov

The effectivity of targeted therapy and immunotherapy in patients with advanced metastatic and non-metastatic cancer of the esophagus and esophago-gastric junction. [2023]

2. China pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). [2021]

4. England pubmed.ncbi.nlm.nih.gov

The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

7. United States pubmed.ncbi.nlm.nih.gov

Long-term efficacy and predictors of pembrolizumab-based regimens in patients with advanced esophageal cancer in the real world. [2023]

8. England pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab and trastuzumab in HER2-positive oesophageal, gastric, or gastro-oesophageal junction cancer: an open-label, single-arm, phase 2 trial. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Immuno-oncology for esophageal cancer. [2021]