What side effects are associated with this type of intervention?

Common treatments for gastroesophageal cancer, particularly those involving PD-1 inhibitors like pembrolizumab, are associated with several side effects. Pembrolizumab can cause severe (≥grade 3) treatment-related adverse effects in about 27% of patients, with common issues including pneumonitis, fatigue, and skin reactions. Other frequent side effects include nausea, vomiting, and diarrhea. In some cases, immune-related adverse events such as endocrine disorders can also occur. These side effects are generally consistent with those observed in other immunotherapy treatments for similar cancers.

What prior FDA approvals exist?

Pembrolizumab, an anti-PD-1 monoclonal antibody, has been approved by the FDA for the treatment of gastroesophageal cancer, particularly for patients with PD-L1-positive tumors. In the KEYNOTE-181 trial, pembrolizumab demonstrated superiority over systemic chemotherapy in patients with advanced/metastatic squamous cell carcinoma (SCC) or adenocarcinoma of the esophagus or gastroesophageal junction, showing improved overall survival and fewer severe adverse events. Other PD-1 inhibitors like avelumab have been studied, but pembrolizumab remains a key FDA-approved option for this indication.

What other types of research exist?

Promising novel alternatives to Pembrolizumab for gastroesophageal cancer patients include: 1) Nivolumab, which has shown efficacy in the ATTRACTION-3 trial for esophageal squamous cell carcinoma. 2) Camrelizumab, which demonstrated positive results in the ESCORT study for advanced or metastatic esophageal squamous cell carcinoma. 3) Tislelizumab, which has been evaluated as a second-line treatment for advanced or metastatic esophageal cancer. These alternatives offer potential options for patients considering treatment in 2024.

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Anti-microtubule agent

Immunotherapy + Anti-angiogenesis + Chemotherapy for Gastroesophageal Cancer (SEQUEL Trial)

Phase 2

Recruiting

Led By Harry H Yoon, MD, MHS

Research Sponsored by Harry H Yoon

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically or cytologically proven adenocarcinoma of the stomach or GEJ

Metastatic, recurrent, or locally advanced unresectable disease

Must not have

Disease progression according to RECIST v1.1 or irRECIST, or treatment intolerance, during prior therapy with an anti-PD-1, anti-PD-L1, or anti- PD-L2 agent

Pre-existing motor or sensory neurotoxicity grade 3 or higher

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial uses a combination of drugs to treat cancer patients who may not respond to standard treatments. The drugs help the immune system fight cancer, block blood supply to tumors, and stop cancer cells from dividing.

Who is the study for?

Adults with advanced stomach or gastroesophageal cancer, good organ function, and an ECOG Performance Status of 0-1. They must provide tissue samples, have measurable disease per RECIST v1.1, not be pregnant or breastfeeding, use effective contraception if of childbearing potential, and agree to follow-up visits.

What is being tested?

The trial tests Pembrolizumab alone followed by combination therapy with Ramucirumab and Paclitaxel for advanced stomach cancers. Patients are randomly assigned to two groups receiving these treatments to compare effectiveness.

What are the potential side effects?

Possible side effects include allergic reactions to the drugs used; fatigue; blood disorders; issues affecting organs like the liver or lungs; gastrointestinal complications such as bleeding or perforation; and increased risk of infection.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is a type of stomach or GEJ cancer confirmed by lab tests.

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My cancer has spread, come back, or can't be removed with surgery.

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I agree to give tissue and blood samples for research and have a cancer that can be biopsied again.

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I cannot provide a tissue sample for medical reasons.

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I am 18 years old or older.

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I have had a biopsy to confirm my cancer before joining the trial or starting treatment.

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I have been mostly active and able to carry on all pre-disease activities without restriction in the last 28 days.

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I am 18 years old or older.

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I am eligible for treatment with pembrolizumab, ramucirumab, and paclitaxel.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My cancer got worse or I couldn't tolerate the treatment with specific immune therapy.

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I do not have severe nerve damage.

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I have had a heart attack or stroke in the last 6 months.

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I have had a solid organ or bone marrow transplant.

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I lost 5% or more of my weight while on anti-PD-1/L1/L2 therapy.

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My heart health meets the study's requirements.

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My liver condition is severe, with significant symptoms like confusion or fluid in the abdomen.

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I haven't had serious wounds, ulcers, or fractures in the last 28 days.

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I have had a GI perforation or am at risk for one in the last 6 months.

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I have not coughed up blood or have a tumor invading major blood vessels.

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I have had severe GI bleeding in the last 3 months.

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I have an autoimmune disease treated with medication in the last 2 years.

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I have had lung conditions that needed steroid treatment.

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I haven't had any cancer treatment with monoclonal antibodies in the last 3 weeks or have recovered from their side effects.

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I have a history of lung inflammation not caused by an infection.

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I am currently being treated for an infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Cohort 1: Evaluate the best overall response rate (BORR) by pooling Arm A and Arm B

Cohort 2: Evaluate Progression free survival (PFS) of Ramucirumab (RAM) plus Paclitaxel plus Pembrolizumab (PEM)

Secondary study objectives

Assess the frequency and severity of adverse events

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm BExperimental Treatment3 Interventions

Pembrolizumab will be administered every 3 weeks in combination with ramucirumab + paclitaxel. The paclitaxel schedule differs between the 2 arms.

Group II: Arm AExperimental Treatment3 Interventions

Pembrolizumab will be administered every 3 weeks in combination with ramucirumab + paclitaxel. The paclitaxel schedule differs between the 2 arms.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ramucirumab

2017

Completed Phase 3

~5050

Paclitaxel

2011

Completed Phase 4

~5450

0 / 25Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for gastroesophageal cancer include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy uses cytotoxic drugs to kill rapidly dividing cancer cells, while targeted therapies like trastuzumab and ramucirumab focus on specific molecular targets such as HER2 and VEGFR2, respectively, to inhibit tumor growth. Immunotherapy, particularly PD-1 inhibitors like pembrolizumab, works by blocking the PD-1 pathway, which cancer cells exploit to evade the immune system. By inhibiting this pathway, pembrolizumab enhances the body's immune response against cancer cells. This is particularly important for gastroesophageal cancer patients as it offers a treatment option that can potentially improve survival rates and quality of life, especially in cases where traditional therapies are less effective.

Esophageal and Esophagogastric Junction Cancers, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.