Investigational Agents + Pembrolizumab for Esophageal Cancer

Recruiting at 69 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

230 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safety and effectiveness of new treatment combinations for individuals with advanced esophageal squamous cell carcinoma (ESCC), a type of cancer in the food pipe, who did not respond to their initial treatment. The trial tests various combinations of the drug pembrolizumab (also known as KEYTRUDA or MK-3475, an immunotherapy) with other treatments to identify the most effective option. Individuals whose cancer progressed after one line of standard treatment, including PD-1/PD-L1-based therapy, might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in participants.

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.

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

Research has shown that sacituzumab tirumotecan is generally well-tolerated by patients. In a previous study, no treatment-related deaths were reported by the time the data was collected, indicating a positive safety profile.

Studies have tested the combination of pembrolizumab with MK-4830 and either paclitaxel or irinotecan in people with advanced esophageal cancer. The trials found the combination to be reasonably safe. Pembrolizumab already has FDA approval for other uses, suggesting some understanding of its safety.

Additionally, researchers have studied pembrolizumab combined with MK-4830 and lenvatinib, focusing on safety. Participants tolerated the treatment, experiencing side effects similar to those seen in other cancer treatments.

For those considering joining a trial, these findings suggest that each treatment option has undergone careful safety evaluation. Discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for esophageal cancer because they offer new ways to potentially enhance the effectiveness of existing therapies. Sacituzumab tirumotecan is a novel drug that targets cancer cells more precisely, which might mean fewer side effects compared to traditional chemotherapy like paclitaxel or irinotecan. The combination of pembrolizumab with MK-4830 and lenvatinib is intriguing because it brings together immune checkpoint inhibitors and a targeted therapy, potentially boosting the body's immune response against cancer cells while also cutting off the tumor's blood supply. These innovative approaches could lead to more effective and tolerable treatment options for patients.

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

Research has shown that sacituzumab tirumotecan, an investigational agent in this trial, may effectively treat cancers like stomach cancer, with 80.5% of patients experiencing disease control and an average response lasting 7.5 months. In this trial, participants may receive sacituzumab tirumotecan at either 4 mg/kg or 5 mg/kg. Another treatment arm involves pembrolizumab combined with MK-4830 and either paclitaxel or irinotecan, which has shown promise in improving outcomes for esophageal cancer, building on its success with other cancers. Additionally, this trial includes an arm where pembrolizumab is combined with MK-4830 and lenvatinib. Studies indicate this combination can significantly improve the time patients live without cancer worsening and increase response rates in some cancers, though results have varied. These findings suggest that each treatment could effectively manage esophageal squamous cell carcinoma, especially for patients who have tried other therapies. ^{1 4 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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 do not have conditions affecting medication absorption.

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Sacituzumab tirumotecan 5 mg/kg Experimental Treatment 7 Interventions

Participants will receive 5 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation.

Group II: Sacituzumab tirumotecan 4 mg/kg 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 III: 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 IV: 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 V: 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

Published Research Related to This Trial

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 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]

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]

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) 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05342636

NCT05342636 | A Study of Combination Therapies With or ... This is a phase I/II multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of investigational agents with pembrolizumab ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38695479/

LEAP-014: first-line lenvatinib + pembrolizumab ... Treatment options for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) are improving.

3. msdclinicaltrials.com msdclinicaltrials.com/trial/nct05342636/

A Study of Combination Therapies With Pembrolizumab in ... This is a phase I/II multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of investigational agents with pembrolizumab.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.TPS487

KEYMAKER-U06 substudy 06A trial in progress: A phase 1 ... Background: Immunotherapy has improved clinical outcomes in esophageal carcinoma; however, patients with advanced esophageal cancer that ...

5. empr.com empr.com/news/mixed-results-for-pembrolizumab-lenvatinib-in-advanced-gastroesophageal-cancer-trial/

Mixed Results for Pembrolizumab/Lenvatinib in Advanced ... Findings showed at the interim analysis, pembrolizumab/lenvatinib treatment statistically significantly improved PFS and objective response rate ...

6. merckclinicaltrials.com merckclinicaltrials.com/trial/nct05342636/

A Study of Combination Therapies With or Without ... This is a phase I/II multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of investigational agents with pembrolizumab ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05319730

NCT05319730 | A Study to Evaluate Investigational Agents ... A Study to Evaluate Investigational Agents With or Without Pembrolizumab (MK-3475) in Participants With Advanced Esophageal Cancer Previously Exposed to ...