78 Participants Needed

Ziv-aflibercept + Pembrolizumab for Cancer

Recruiting at 8 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

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, you cannot participate if you have had chemotherapy, targeted therapy, or radiotherapy within 4 weeks before the study, or if you are on certain immunosuppressive therapies. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Ziv-aflibercept and Pembrolizumab for cancer?

Pembrolizumab has shown effectiveness in treating non-small cell lung cancer by helping the immune system attack cancer cells. Ziv-aflibercept has been effective in improving survival in patients with metastatic colorectal cancer when used with other chemotherapy drugs.12345

Is the combination of Ziv-aflibercept and Pembrolizumab safe for humans?

Pembrolizumab (also known as KEYTRUDA) has been shown to be generally safe in humans, with common side effects including tiredness, rash, itching, and diarrhea. Ziv-aflibercept (also known as Zaltrap) has been used safely in combination with other treatments for cancer, but it can increase some chemotherapy-related side effects. Both drugs have been tested in various conditions, showing a favorable safety profile.56789

What makes the drug combination of Ziv-aflibercept and Pembrolizumab unique for cancer treatment?

This drug combination is unique because it combines Ziv-aflibercept, which inhibits blood vessel growth in tumors, with Pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This dual approach targets both the tumor's blood supply and enhances the body's immune response against cancer.1261011

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of ziv-aflibercept when given together with pembrolizumab in treating patients with solid tumors that that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Ziv-afibercept works by decreasing blood and nutrient supply to the tumor, which may result in shrinking the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving ziv-aflibercept together with pembrolizumab may be a better treatment for patients with advanced solid tumors.

Research Team

FS

Frank S Hodi

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

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.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document
Your hemoglobin level is at least 9 g/dL or 5.6 mmol/L.
My cancer is resistant to PD-1 treatment.
See 22 more

Exclusion Criteria

I haven't had severe GI bleeding or uncontrollable blood clot issues in the last 3 months.
I have a history of cancer.
I am on a full dose of Coumadin for blood thinning.
See 22 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab and ziv-aflibercept intravenously. Cycles repeat every 2 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

Up to 2 years
Bi-weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, including CT scans, MRIs, blood sample collection, and tumor biopsy.

12 weeks

Treatment Details

Interventions

  • Pembrolizumab
  • Ziv-Aflibercept
Trial Overview 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.
Participant Groups
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.

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

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

Aflibercept combined with FOLFIRI significantly improved overall survival in patients with metastatic colorectal cancer (mCRC) previously treated with oxaliplatin, showing median survival of 12.5 months compared to 11.7 months with placebo.
The treatment effect of aflibercept was consistent across various patient subgroups, including those with or without prior bevacizumab treatment, indicating its broad efficacy in this patient population.
Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial.Tabernero, J., Van Cutsem, E., Lakomý, R., et al.[2022]
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.
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]
Intravitreal injections of ziv-aflibercept (IVI-ZA) over 48 weeks were found to be safe, with no significant changes in electroretinogram results or any systemic or ocular complications in the seven patients with diabetic macular edema (DME).
The treatment led to a significant improvement in best-corrected visual acuity (BCVA) after the first injection, which was maintained throughout the study, and a notable decrease in central retinal thickness (CRT), indicating its efficacy in managing DME.
Intravitreal Ziv-Aflibercept for Diabetic Macular Edema: 48-Week Outcomes.de Andrade, GC., de Oliveira Dias, JR., Maia, A., et al.[2019]

References

Evaluation of efficacy and safety markers in a phase II study of metastatic colorectal cancer treated with aflibercept in the first-line setting. [2022]
Ziv-aflibercept: a novel angiogenesis inhibitor for the treatment of metastatic colorectal cancer. [2022]
Aflibercept and Docetaxel versus Docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: a randomized, controlled phase III trial. [2022]
Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. [2022]
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]
Intravitreal Ziv-Aflibercept for Diabetic Macular Edema: 48-Week Outcomes. [2019]
Pembrolizumab in the management of metastatic melanoma. [2020]
[Aflibercept (Zaltrap(®)) approved in metastatic colorectal cancer]. [2013]
FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]
Ziv-aflibercept: A cost-effective, off-label, highly potent antagonist of vascular endothelial growth factor. [2023]
11.United Statespubmed.ncbi.nlm.nih.gov
Safety and Efficacy of Ziv-Aflibercept in the Treatment of Refractory Diabetic Macular Edema. [2022]
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