Investigational Agents + Pembrolizumab for Esophageal Cancer
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Merck Sharp & Dohme LLC
No Placebo Group
Breakthrough Therapy
Approved in 3 jurisdictions
Trial Summary
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.
Is the drug Pembrolizumab a promising treatment for esophageal cancer?Yes, Pembrolizumab is a promising drug for esophageal cancer. It has been approved for use with chemotherapy in advanced cases, showing potential in improving treatment outcomes.14567
What safety data is available for Pembrolizumab in esophageal cancer treatment?Pembrolizumab, also known as Keytruda or MK-3475, has been approved for use in metastatic or locally advanced esophageal or gastroesophageal junction cancer in combination with chemotherapy. Safety data from various studies indicate that common adverse reactions include fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions can include pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. These findings are consistent with safety profiles observed in other cancers treated with Pembrolizumab, such as melanoma and non-small cell lung cancer.12456
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop your current medications. However, you must not be on chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of the study medication. It's best to discuss your current medications with the trial team.
What data supports the idea that Investigational Agents + Pembrolizumab for Esophageal Cancer is an effective treatment?The available research shows that Pembrolizumab, when combined with chemotherapy, has been approved for treating advanced esophageal cancer. This suggests it has shown effectiveness in clinical trials. Additionally, studies have reported increases in survival rates for patients using Pembrolizumab, indicating its potential as a beneficial treatment option. Compared to other treatments, Pembrolizumab is one of the few recommended biologic therapies, highlighting its importance in treating this type of cancer.34567
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
My esophageal cancer cannot be removed by surgery and has spread.
My blood pressure is under control, with or without medication.
My cancer progressed after one standard treatment including a platinum drug and anti-PD1/PD-L1 therapy.
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 have or had inflammatory bowel disease and need or needed medication to suppress my immune system.
I have had Hepatitis B or currently have Hepatitis C.
I have not had significant GI bleeding or related conditions in the past 3 months.
My cancer has spread to nearby organs like the aorta or windpipe.
I have lost more than 10% of my weight in the last 2 months.
I have a severe eye condition that affects my cornea or eyelids.
I have an immune system disorder or have been on steroids or other immune-weakening drugs in the last week.
I have been treated for an autoimmune disease in the last 2 years.
I have received an organ or tissue transplant from another person.
Treatment Details
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.
4Treatment groups
Experimental Treatment
Active Control
Group I: Sacituzumab tirumotecanExperimental Treatment5 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 irinotecanExperimental Treatment4 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 + lenvatinibExperimental Treatment3 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 irinotecanActive Control2 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
Hematology-Oncology Associates of Central NY, P.C. ( Site 4925)East Syracuse, NY
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Who is running the clinical trial?
Merck Sharp & Dohme LLCLead Sponsor
References
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. [2020]Biologic agents, including targeted antibodies as well as immunomodulators, are demonstrating unparalleled development and study across the entire spectrum of human malignancy. This review summarizes the current state of biologic therapies for esophageal, esophagogastric, and gastric malignancies, including those that target human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), c-Met, mechanistic target of rapamycin (mTOR) and immunomodulators. We focus primarily on agents that have been included in phase II and III clinical trials in locally advanced, progressive, or metastatic esophageal and gastric malignancies. At this time, only two biologic therapies are recommended by the National Comprehensive Cancer Network (NCCN): trastuzumab for patients with esophageal/esophagogastric or gastric adenocarcinomas with HER2 overexpression and ramucirumab, a VEGFR-2 inhibitor, as a second-line therapy for metastatic disease. However, recent reports of increases in overall and progression-free survival for agents including pertuzumab, apatinib, and pembrolizumab will likely increase the use of targeted biologic therapy in clinical practice for esophageal and gastric malignancies.
Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). [2021]To investigate the safety and activity of preoperative pembrolizumab combined with chemoradiotherapy for resectable oesophageal squamous cell carcinoma (ESCC) (ClinicalTrials.gov number, NCT03792347).
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]Pembrolizumab (Keytruda) has been approved to treat metastatic or locally advanced esophageal or gastroesophageal junction cancer. It is used in combination with platinum- and fluoropyrimidine-based chemotherapy.
Phase II study of pembrolizumab in refractory esophageal cancer with correlates of response and survival. [2022]Immune checkpoint inhibitors have revolutionized cancer treatment, but the benefits in refractory patients with esophageal cancer have been modest. Predictors of response as well as new targets for novel therapeutic combinations are needed. In this phase 2 clinical trial, we tested single-agent pembrolizumab in patients with advanced esophageal cancer, who received at least one prior line of therapy.