Investigational Agents + Pembrolizumab for Esophageal Cancer

Recruiting at 58 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune, CNS metastases, HIV, others

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

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 92 weeks

200 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or immunosuppressive therapy, you must stop these at least 7 days before starting the study medication.

What data supports the effectiveness of the drug pembrolizumab for esophageal cancer?

Pembrolizumab has been approved for treating esophageal or gastroesophageal cancer when combined with certain chemotherapies, and studies have shown it can improve survival in these cancers. Additionally, pembrolizumab has shown promise in other cancers, like lung cancer, suggesting its potential effectiveness in treating esophageal cancer. ^{1 2 3 4 5}

Is pembrolizumab safe for use in humans?

Pembrolizumab (also known as Keytruda or MK-3475) has been used in various clinical trials and approved for several cancers, showing it is generally safe for humans. Common side effects include fatigue, cough, nausea, and rash, while some people may experience immune-related issues like inflammation of the lungs or liver. ^{1 2 3 6 7}

How is the drug pembrolizumab unique for treating esophageal cancer?

Pembrolizumab is unique because it is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells, and it is used in combination with chemotherapy for esophageal cancer, which is different from traditional treatments that may not involve the immune system. ^{1 2 3 5 6}

What is the purpose of this trial?

This is a Phase 1/2, multicenter, randomized, open-label umbrella platform study to evaluate the safety and efficacy of investigational agents with or without pembrolizumab and/or chemotherapy, for the treatment of participants with second line (2L) esophageal squamous cell carcinoma (ESCC) who have previously been exposed to PD-1/PD-L1 based treatment.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for individuals with advanced esophageal cancer who have already tried treatments targeting PD-1/PD-L1 proteins. Participants should be ready for second-line therapy and meet other health criteria set by the study.

Inclusion Criteria

Has an evaluable baseline tumor sample (newly obtained or archival) for analysis

My cancer progressed after one standard treatment including a platinum drug and anti-PD1/PD-L1 therapy.

My side effects from past cancer treatments are mild or gone, except for some hormone issues or mild nerve pain.

Exclusion Criteria

I have active brain metastases or cancer in my brain's lining.

I haven't had serious heart problems in the last year.

I do not have conditions affecting medication absorption.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Participants are monitored for adverse events and dose-limiting toxicities

3 weeks

Treatment

Participants receive investigational agents with or without pembrolizumab and/or chemotherapy

Up to 92 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 189 weeks

Treatment Details

Interventions

• Pembrolizumab

Trial Overview The study tests various agents, like Sacituzumab tirumotecan and Lenvatinib, with or without Pembrolizumab (a known immunotherapy drug) and/or chemotherapy to see their effects on esophageal cancer after first treatment has failed.

Participant Groups

Group I: Sacituzumab tirumotecan Experimental Treatment 7 Interventions

Participants will receive 4 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation.

Group II: Pembrolizumab + MK-4830 + paclitaxel or irinotecan Experimental Treatment 4 Interventions

Participants receive pembrolizumab 200 mg IV once every 3 weeks (Q3W) for up to 35 cycles (cycle=21 days) or until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + paclitaxel 80-100 mg/m\^2 IV on days 1, 8, and 15 every 28-day cycle until PD or discontinuation or irinotecan 180 mg/m\^2 180 mg/m\^2 on day 1 every 14-day cycle until PD or discontinuation.

Group III: Pembrolizumab + MK-4830 + lenvatinib Experimental Treatment 3 Interventions

Participants receive pembrolizumab 200 mg IV Q3W up to 35 cycles (cycle=21 days) until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + lenvatinib 20 mg oral administration every day until PD or discontinuation.

Group IV: Paclitaxel or irinotecan Active Control 2 Interventions

Participants receive paclitaxel 80-100 mg/m\^2 intravenously (IV) on days 1, 8, and 15 every 28-day cycle until progressive disease (PD) or discontinuation, or irinotecan 180 mg/m\^2 IV on day 1 of every 14-day cycle until PD or discontinuation.

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?

Merck Sharp & Dohme LLC

Lead 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

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]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

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]

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]

In a phase 2 trial involving 49 patients with refractory esophageal cancer, pembrolizumab showed a modest overall response rate of 8% and a median overall survival of 5.8 months, indicating limited efficacy as a single-agent treatment.

Baseline levels of circulating CXCL10 were identified as a strong predictor of survival, while other markers of T cell exhaustion were found to be elevated in PD-L1-positive patients, suggesting potential for combination therapies targeting these pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of pembrolizumab in refractory esophageal cancer with correlates of response and survival. de Klerk, LK., Patel, AK., Derks, S., et al.[2022]

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]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

References

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

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

4. China pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Phase II study of pembrolizumab in refractory esophageal cancer with correlates of response and survival. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]