What side effects are associated with this type of intervention?

Checkpoint inhibitor immunotherapy for esophageal cancer, such as pembrolizumab, nivolumab, and ipilimumab, can cause a range of side effects. Common side effects include pneumonitis, skin reactions, endocrine events, and gastrointestinal issues like diarrhea. Severe adverse events may include pneumonia, febrile neutropenia, anemia, acute kidney injury, and respiratory failure. While rare, fatal adverse reactions have also been reported.

What prior FDA approvals exist?

The FDA has approved several checkpoint inhibitor immunotherapy drugs for the treatment of esophageal cancer. Pembrolizumab, an anti-PD-1 monoclonal antibody, has shown superiority over systemic chemotherapy in the KEYNOTE-181 trial for second-line therapy in patients with advanced or metastatic esophageal squamous cell carcinoma (SCC) or adenocarcinoma. Nivolumab, another anti-PD-1 antibody, has also been approved based on its efficacy in improving overall survival and progression-free survival in patients with advanced gastric, esophageal, or gastroesophageal junction cancer, as demonstrated in trials like CheckMate-032. These approvals highlight the role of immune checkpoint inhibitors in enhancing the immune system's ability to target and destroy cancer cells in esophageal cancer.

What other types of research exist?

Promising novel alternatives to checkpoint inhibitor immunotherapy for esophageal cancer patients include combination therapies involving chemotherapy and other immunotherapy agents, such as nivolumab plus ipilimumab. Additionally, personalized antibody treatments and therapies targeting specific biomarkers like dMMR/MSI-H or high TMB are emerging as potential options. Ongoing clinical trials and research into these combination and targeted therapies may provide new avenues for treatment in 2024.

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Chemotherapy

Immunotherapy Combinations for Esophageal Cancer

Phase 1 & 2

Waitlist Available

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

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

Must have

Histologically or cytologically confirmed diagnosis of squamous cell carcinoma or adenocarcinoma of the esophagus in locally advanced or metastatic disease;

Age >/= 18 years

Must not have

Symptomatic, untreated, or actively progressing central nervous system (CNS) Metastases

Serious or non-healing wound, peptic ulcer, or bone fracture within 28 days prior to initiation of study treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up pre-dose (0 hr) on day 1 of priming period (1 week prior to day 1 of cycle 1) up to 30 days after last dose (up to approximately 3-6 years) (detailed timeframe is provided in outcome measure description)

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of chemotherapy and immunotherapy in patients with advanced gastric and esophageal cancers. It aims to see if this combination is safe and effective, especially for those who haven't responded to other treatments or haven't been treated before. Combination therapies involving chemotherapy and immunotherapy have shown promising results in initial clinical trials for cancer treatment.

Who is the study for?

Adults with advanced gastric or gastroesophageal junction cancer, or esophageal cancer who have not had certain treatments. They must be in good physical condition (ECOG 0-1), expect to live at least 3 months, and agree to use contraception. Excluded are those with uncontrolled hypertension, recent severe infections, significant heart disease, autoimmune diseases, HIV/HBV/HCV infection, CNS metastases risk factors for bleeding disorders.

What is being tested?

The trial is testing combinations of immunotherapy and chemotherapy in patients with advanced gastric or esophageal cancers. It includes drugs like Atezolizumab and Tiragolumab alongside standard chemotherapies such as Cisplatin and Paclitaxel. Patients will be randomly assigned to different treatment groups.

What are the potential side effects?

Possible side effects include reactions related to the immune system affecting organs, infusion-related reactions from the drug administration process itself, fatigue, gastrointestinal issues like nausea or diarrhea, blood-related problems including anemia or clotting issues, increased risk of infections.

Eligibility Criteria

Inclusion Criteria

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

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My esophagus cancer is confirmed and is either advanced or has spread.

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I am 18 years old or older.

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I am fully active or can carry out light work.

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My esophageal cancer is confirmed and has spread or is very advanced.

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I agree to not have sex or use birth control and not donate sperm.

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My gastric cancer is HER2-negative.

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I can take care of myself and am up and about more than half of my waking hours.

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I am able to care for myself and perform daily activities.

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I am fully active or can carry out light work.

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My cancer is advanced and cannot be removed by surgery.

Exclusion Criteria

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

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I have brain metastases that are untreated or getting worse.

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

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I have a history of serious bowel problems or surgeries.

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My blood pressure is high (over 150/90) despite taking medication.

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I have a serious heart condition.

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I have high calcium levels in my blood that aren't controlled or cause symptoms.

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I have a history of specific lung conditions or signs of lung inflammation on a recent CT scan.

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I have a condition that causes significant bleeding.

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I have had a previous transplant of stem cells or an organ.

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I haven't had major surgery in the last 4 weeks and don't expect to need one during the study.

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I am currently on blood thinners like warfarin or heparin for treatment.

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I am at high risk for developing an esophageal fistula.

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I have active tuberculosis.

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I have had lung conditions like pulmonary fibrosis or pneumonitis, or my CT scan shows active pneumonitis.

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I have had cancer spread to the lining of my brain and spinal cord.

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I have brain metastases that are untreated or getting worse.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ pre-dose (0 hr) on day 1 of priming period (1 week prior to day 1 of cycle 1) up to 30 days after last dose (up to approximately 3-6 years) (detailed timeframe is provided in outcome measure description)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~pre-dose (0 hr) on day 1 of priming period (1 week prior to day 1 of cycle 1) up to 30 days after last dose (up to approximately 3-6 years) (detailed timeframe is provided in outcome measure description)

This trial's timeline: 3 weeks for screening, Varies for treatment, and pre-dose (0 hr) on day 1 of priming period (1 week prior to day 1 of cycle 1) up to 30 days after last dose (up to approximately 3-6 years) (detailed timeframe is provided in outcome measure description) for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Percentage of Participants With ADA to BL-8040

Plasma Concentration of BL-8040

Plasma Concentration of PEGPH20

Awards & Highlights

No Placebo-Only Group

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

Trial Design

12Treatment groups

Experimental Treatment

Active Control

Group I: 2L-4: Atezo + Linagliptin (Gastric Cancer)Experimental Treatment2 Interventions

Participants in the 2L-4 Gastric Cancer arm received atezolizumab in combination with linagliptin. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.

Group II: 2L-3: Atezo + BL-8040 (Gastric Cancer)Experimental Treatment2 Interventions

Participants in the 2L-3 Gastric Cancer arm received atezolizumab in combination with BL-8040. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.

Group III: 2L-2: Atezo + PEGPH20 (Gastric Cancer)Experimental Treatment2 Interventions

Participants in the 2L-2 Gastric Cancer arm received atezolizumab in combination with PEGylated recombinant human hyaluronidase (PEGPH20). Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.

Group IV: 2L-1: Atezo + Cobi (Gastric Cancer)Experimental Treatment2 Interventions

Participants in the 2L-1 Gastric Cancer arm received atezolizumab in combination with cobimetinib. Enrollment completed as of October 2019.

Group V: 1L-A: mFOLFOX6 + Atezo + Cobi (Gastric Cancer)Experimental Treatment5 Interventions

Participants in the 1L-A Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab plus cobimetinib. No longer enrolling participants as of June 2018.

Group VI: 1L-A2: Atezo+mFOLFOX6 followed by Atezo+Cobi (Gastric Cancer)Experimental Treatment5 Interventions

Participants in the 1L-A2 Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab during cycles 1 and 2 followed by atezolizumab plus cobimetinib during cycles 3 and beyond. No longer enrolling participants as of June 2018.

Group VII: 1L-3: Atezo+Tiragolumab (Esophageal Cancer Cohort)Experimental Treatment2 Interventions

Participants in the 1L-3 Esophageal Cancer arm will receive atezolizumab + tiragolumab treatment. Participants from the cisplatin + 5-FU esophageal cancer cohort arm may be permitted to enroll in this arm if they progress after receiving chemotherapy.

Group VIII: 1L-2: Atezo+Cisplatin+5-FU (Esophageal Cancer Cohort)Experimental Treatment3 Interventions

Participants in the 1L-2 Esophageal Cancer arm will receive atezolizumab in combination with chemotherapy.

Group IX: 1L-1:Atezo+Tiragolumab+Cisplatin+5FU(Esophageal Cancer Cohort)Experimental Treatment4 Interventions

Participants in the 1L-1 Esophageal Cancer arm will receive atezolizumab in combination with tiragolumab and chemotherapy.

Group X: 2L-Control: Ramucirumab + Paclitaxel (Gastric Cancer)Active Control2 Interventions

Participants in the 2L Gastric Cancer Control arm received ramucirumab plus paclitaxel. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.

Group XI: 1L-Control: mFOLFOX6 (Gastric Cancer)Active Control3 Interventions

Participants in the 1L Gastric Cancer Control arm will receive modified FOLFOX6 (mFOLFOX6) treatment consisting of 5-fluorouracil (5-FU), leucovorin (folinic acid), and oxaliplatin. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria. No longer enrolling participants as of June 2018.

Group XII: 1L-Control: Cisplatin+5-FU (Esophageal Cancer Cohort)Active Control2 Interventions

Participants in the 1L-Control Eophageal Cancer arm will receive chemotherapy.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cobimetinib

2017

Completed Phase 3

~3630

5-Fluorouracil (5-FU)

2003

Completed Phase 3

~5560

Oxaliplatin

2011

Completed Phase 4

~2890

BL-8040

2014

Completed Phase 2

~560

Cisplatin

2013

Completed Phase 3

~3120

Atezolizumab

2016

Completed Phase 3

~5860

Leucovorin

2005

Completed Phase 4

~6010

Tiragolumab

2019

Completed Phase 3

~2330

Linagliptin

2010

Completed Phase 4

~19930

0 / 26Eligibility 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

Checkpoint inhibitor immunotherapy, such as pembrolizumab and nivolumab, works by blocking proteins like PD-1 or PD-L1 that cancer cells use to evade the immune system. By inhibiting these checkpoints, the therapy enhances the immune system's ability to recognize and attack cancer cells. This is particularly important for esophageal cancer patients because it offers a targeted approach that can improve survival rates and provide an option for those who have not responded to traditional chemotherapy. These treatments are being actively studied and have shown promise in improving outcomes for patients with advanced or metastatic esophageal cancer.

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