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Monoclonal Antibodies

Ziv-aflibercept + Pembrolizumab for Cancer

Phase 1

Waitlist Available

Led By Frank S Hodi

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

Patients must have PD-1 resistant melanoma, PD-1 resistant renal cancer, or sarcoma for dose expansion part 2

Renal cell patients must have had at least one prior vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI)

Must not have

History within 3 months prior to treatment of grade 3-4 gastrointestinal (GI) bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolus, or other uncontrolled thromboembolic event

History of active malignancy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up time from start of trial treatment to death from any cause, assessed up to 12 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing ziv-aflibercept given with pembrolizumab to see if it is safe and effective in treating patients with advanced solid tumors.

Who is the study for?

Adults with advanced solid tumors, specifically melanoma, renal cancer, ovarian cancer or colorectal cancer that's spread and is resistant to certain treatments. Participants must have adequate organ function, no more than two prior therapies for metastatic disease, and not be pregnant or breastfeeding. They should agree to use contraception and not have a history of severe autoimmune diseases or other conditions that could interfere with the trial.

What is being tested?

The trial is testing the combination of ziv-aflibercept (which cuts off blood supply to tumors) with pembrolizumab (an immunotherapy drug). It aims to find the safest dose while observing how well this combo works against advanced cancers by leveraging the body's immune system.

What are the potential side effects?

Potential side effects include reactions at the infusion site, fatigue, changes in blood pressure and bleeding risks due to ziv-aflibercept; pembrolizumab may cause immune-related issues like inflammation in organs as well as flu-like symptoms.

Eligibility Criteria

Inclusion Criteria

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

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My cancer is resistant to PD-1 treatment.

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I have had treatment with a VEGF inhibitor for my kidney cancer.

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My kidney function is normal or only slightly below normal.

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I can provide a sample of my tumor, either from previous or new biopsies.

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I have confirmed metastatic melanoma, kidney, ovarian, or colorectal cancer.

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My ovarian cancer does not respond to platinum-based treatments.

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I have had 2 or fewer treatments for my cancer that has spread.

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My colorectal cancer did not respond to a treatment that included oxaliplatin.

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I am 18 years old or older.

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My cancer has spread and this was confirmed through testing.

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I am mostly self-sufficient and can carry out daily activities.

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My liver enzymes are within the required range, even with liver metastases.

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My melanoma or kidney cancer didn't respond to previous PD-1/PD-L1 therapy.

Exclusion Criteria

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

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I haven't had severe GI bleeding or uncontrollable blood clot issues in the last 3 months.

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I have a history of cancer.

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I am on a full dose of Coumadin for blood thinning.

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My cancer involves areas at high risk of bleeding, like the bowel or lungs.

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I have had a condition where my lymphocytes grow abnormally.

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My high blood pressure is not well-managed.

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I have cancer that has spread to my brain.

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I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

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I have another cancer that is getting worse or needs treatment.

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I have open sores on my skin.

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I have cancer cells in the fluid around my brain and spinal cord.

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I have been treated with specific immune-targeting medications before.

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I have an autoimmune disease that needed treatment in the last 3 months or have had a severe case before.

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I haven't taken steroids or immunosuppressants in the last 7 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ time from start of trial treatment to death from any cause, assessed up to 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~time from start of trial treatment to death from any cause, assessed up to 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and time from start of trial treatment to death from any cause, assessed up to 12 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Recommended combination dose of ziv-aflibercept and pembrolizumab

Secondary study objectives

Objective response rate (ORR)

Overall survival

Progression-free survival

+1 more

Other study objectives

Changes in antigen specific responses to known melanoma antigen epitopes (melanoma antigen recognized by T cells 1, NY-ESO-1)

Effects on tumor vasculature and vascular active molecules

Humoral and cellular immune responses

+2 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (pembrolizumab and ziv-aflibercept)Experimental Treatment6 Interventions

Patients receive pembrolizumab intravenously (IV) over approximately 30 minutes and ziv-aflibercept IV over 1-2 hours on day 1. Cycles repeat every 2 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, blood sample collection and tumor biopsy throughout the study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biopsy

2014

Completed Phase 4

~1150

Computed Tomography

2017

Completed Phase 2

~2790