CLINICAL TRIALS PROFILE FOR ZALTRAP

All Clinical Trials for ZALTRAP

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00284141 ↗	Study of AVE0005 (VEGF Trap) in Locally Advanced or Metastatic Platinum- and Erlotinib- Resistant Non-small-cell-lung Adenocarcinoma	Completed	Regeneron Pharmaceuticals	Phase 2	2006-01-01	This study evaluated the efficacy and safety of aflibercept in the treatment of participants with advanced chemoresistant non-small cell lung adenocarcinoma (NSCLA). Primary objective: - To determine the overall objective response rate (ORR) of AVE0005 (ziv-aflibercept, aflibercept, VEGF trap, ZALTRAP®) 4.0 mg/kg intravenously (IV) every 2 weeks in participants with platinum- and erlotinib-resistant, locally advanced or metastatic NSCLA. Secondary objective: - To assess duration of response (DR), progression-free survival (PFS), and overall survival (OS) in this participant population - To evaluate the safety profile of IV AVE0005 (ziv-aflibercept, aflibercept, VEGF trap, ZALTRAP®). This study employed an Independent Review Committee (IRC) for radiological tumor assessments. For all tumor assessment-related efficacy variables, two analyses were performed: the primary analysis was based on Independent Review Committee (IRC) reviewed data and the secondary analysis was based on Investigator evaluation. In addition, both Response Evaluation Criteria In Solid Tumors (RECIST) and Modified Response Evaluation Criteria In Solid Tumors (mRECIST) were used to assess tumors. Where as RECIST criteria only consider the longest diameter of the tumors for calculations pertaining to changes in tumor size, mRECIST assessments also account for the differences in the cavities of lesions observed in non-small-cell lung cancer (NSCLC). Responses based on RECIST and mRECIST are reported.
NCT00284141 ↗	Study of AVE0005 (VEGF Trap) in Locally Advanced or Metastatic Platinum- and Erlotinib- Resistant Non-small-cell-lung Adenocarcinoma	Completed	Sanofi	Phase 2	2006-01-01	This study evaluated the efficacy and safety of aflibercept in the treatment of participants with advanced chemoresistant non-small cell lung adenocarcinoma (NSCLA). Primary objective: - To determine the overall objective response rate (ORR) of AVE0005 (ziv-aflibercept, aflibercept, VEGF trap, ZALTRAP®) 4.0 mg/kg intravenously (IV) every 2 weeks in participants with platinum- and erlotinib-resistant, locally advanced or metastatic NSCLA. Secondary objective: - To assess duration of response (DR), progression-free survival (PFS), and overall survival (OS) in this participant population - To evaluate the safety profile of IV AVE0005 (ziv-aflibercept, aflibercept, VEGF trap, ZALTRAP®). This study employed an Independent Review Committee (IRC) for radiological tumor assessments. For all tumor assessment-related efficacy variables, two analyses were performed: the primary analysis was based on Independent Review Committee (IRC) reviewed data and the secondary analysis was based on Investigator evaluation. In addition, both Response Evaluation Criteria In Solid Tumors (RECIST) and Modified Response Evaluation Criteria In Solid Tumors (mRECIST) were used to assess tumors. Where as RECIST criteria only consider the longest diameter of the tumors for calculations pertaining to changes in tumor size, mRECIST assessments also account for the differences in the cavities of lesions observed in non-small-cell lung cancer (NSCLC). Responses based on RECIST and mRECIST are reported.
NCT00327171 ↗	Study of AVE0005 (VEGF Trap) in Patients With Chemoresistant Advanced Ovarian Cancer	Completed	Regeneron Pharmaceuticals	Phase 2	2006-05-01	This study evaluated outcomes in participants with advanced ovarian epithelial adenocarcinoma receiving aflibercept. The primary objective was to compare the objective response rate of Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) 4.0 mg/kg and 2.0 mg/kg, administered intravenously (IV) every 2 weeks with historical control in participants with advanced ovarian epithelial (including fallopian tube and primary peritoneal) adenocarcinoma resistant to platinum and topotecan and/or liposomal doxorubicin. The secondary objectives was to further assess efficacy, safety, pharmacokinetics, potential biological and pharmacogenomic markers of study drug activity, and health-related quality of life. This study employed an Independent Review Committee (IRC) for radiological tumor assessments. For all tumor assessment-related efficacy variables, two analyses were performed: the primary analysis was based on Independent Review Committee (IRC) reviewed data and the secondary analysis was based on Investigator evaluation. If an endpoint was evaluated by the IRC, the IRC reviewed data is reported for this study.
NCT00327171 ↗	Study of AVE0005 (VEGF Trap) in Patients With Chemoresistant Advanced Ovarian Cancer	Completed	Sanofi	Phase 2	2006-05-01	This study evaluated outcomes in participants with advanced ovarian epithelial adenocarcinoma receiving aflibercept. The primary objective was to compare the objective response rate of Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) 4.0 mg/kg and 2.0 mg/kg, administered intravenously (IV) every 2 weeks with historical control in participants with advanced ovarian epithelial (including fallopian tube and primary peritoneal) adenocarcinoma resistant to platinum and topotecan and/or liposomal doxorubicin. The secondary objectives was to further assess efficacy, safety, pharmacokinetics, potential biological and pharmacogenomic markers of study drug activity, and health-related quality of life. This study employed an Independent Review Committee (IRC) for radiological tumor assessments. For all tumor assessment-related efficacy variables, two analyses were performed: the primary analysis was based on Independent Review Committee (IRC) reviewed data and the secondary analysis was based on Investigator evaluation. If an endpoint was evaluated by the IRC, the IRC reviewed data is reported for this study.
NCT00327444 ↗	Study of the Effect of Intravenous AVE0005 (VEGF Trap) in Advanced Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites	Completed	Regeneron Pharmaceuticals	Phase 2/Phase 3	2006-07-01	This study was designed to characterize the effect of aflibercept in participants with advanced chemoresistant ovarian cancer. Primary objective: Compare the effect of aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) to placebo treatment on repeat paracentesis in symptomatic malignant ascites in participants with advanced ovarian cancer Secondary objectives: Safety, tolerability, paracentesis-related parameters, participant-reported outcome.
NCT00327444 ↗	Study of the Effect of Intravenous AVE0005 (VEGF Trap) in Advanced Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites	Completed	Sanofi	Phase 2/Phase 3	2006-07-01	This study was designed to characterize the effect of aflibercept in participants with advanced chemoresistant ovarian cancer. Primary objective: Compare the effect of aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) to placebo treatment on repeat paracentesis in symptomatic malignant ascites in participants with advanced ovarian cancer Secondary objectives: Safety, tolerability, paracentesis-related parameters, participant-reported outcome.
NCT00390234 ↗	Ziv-aflibercept in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gynecologic Soft Tissue Sarcoma	Completed	National Cancer Institute (NCI)	Phase 2	2006-09-01	This phase II trial is studying how well ziv-aflibercept works in treating patients with locally advanced, unresectable or metastatic gynecologic soft tissue sarcoma. Ziv-aflibercept may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Clinical Trial Conditions for ZALTRAP

Condition Name

Condition Name for ZALTRAP
Intervention	Trials
Recurrent Colon Cancer	3
Recurrent Rectal Cancer	3
Metastatic Colorectal Cancer	3
Esophageal Cancer	2

Condition MeSH

Condition MeSH for ZALTRAP
Intervention	Trials
Colorectal Neoplasms	13
Rectal Neoplasms	6
Ovarian Neoplasms	6
Neoplasms	4

Clinical Trial Locations for ZALTRAP

Trials by Country

Trials by Country for ZALTRAP
Location	Trials
United States	66
Canada	7
Greece	4
Italy	3
Spain	3

Trials by US State

Trials by US State for ZALTRAP
Location	Trials
California	6
Virginia	4
Texas	4
New Jersey	4
New York	3

Clinical Trial Progress for ZALTRAP

Clinical Trial Phase

Clinical Trial Phase for ZALTRAP
Clinical Trial Phase	Trials
Phase 3	1
Phase 2/Phase 3	2
Phase 2	19

Clinical Trial Status

Clinical Trial Status for ZALTRAP
Clinical Trial Phase	Trials
Completed	18
Withdrawn	5
Recruiting	5

Clinical Trial Sponsors for ZALTRAP

Sponsor Name

Sponsor Name for ZALTRAP
Sponsor	Trials
Sanofi	11
National Cancer Institute (NCI)	9
Regeneron Pharmaceuticals	7

Sponsor Type

Sponsor Type for ZALTRAP
Sponsor	Trials
Other	22
Industry	21
NIH	9

Clinical Trials Update, Market Analysis, and Projection for ZALTRAP

Last updated: November 16, 2025

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Introduction

ZALTRAP (ziv-aflibercept) is an anti-angiogenic agent developed by Regeneron Pharmaceuticals, primarily approved for the treatment of metastatic colorectal cancer (mCRC). Its mechanism involves binding to vascular endothelial growth factors (VEGF-A, VEGF-B) and placental growth factor (PlGF), inhibiting tumor angiogenesis. Despite initial approvals, the therapeutic landscape is evolving, with ongoing clinical trials and market dynamics influencing ZALTRAP’s future position.

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Clinical Trials Landscape: Current Status and Developments

FDA and Regulatory Milestones

Initially approved in 2012, ZALTRAP received FDA approval for metastatic colorectal cancer in combination with FOLFIRI (a chemotherapy regimen). The approval was based on the Phase III VELOUR trial, which demonstrated a significant survival benefit compared to chemotherapy alone [1]. However, subsequent regulatory reviews and label updates have limited the drug’s use, with some regions not granting widespread approval.

Ongoing and Recently Completed Trials

Despite its initial success, ZALTRAP's clinical development has faced challenges, with limited recent trials focusing on expanding its indications. The VELOUR trial remains the cornerstone, with ongoing post-marketing studies examining long-term safety and comparative effectiveness.

• Additional indications: Investigations into ZALTRAP for other cancers, such as pancreatic and non-small cell lung cancer (NSCLC), have been initiated but have yet to yield successful results or regulatory approval [2].

• Combination therapies: Trials assessing ZALTRAP with newer immunotherapy agents, like PD-1 inhibitors, are in early phases, aiming to evaluate synergistic effects in resistant cancers [3].

Clinical Trial Challenges

The complexity of angiogenesis pathways and the advent of more effective or targeted therapies has somewhat limited ZALTRAP’s clinical pipeline. Moreover, the drug’s toxicity profile—namely hypertension, bleeding, and proteinuria—has impacted its acceptance in some studies.

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Market Analysis: Current Position and Competitive Landscape

Market Share and Sales Performance

Following its initial FDA approval, ZALTRAP experienced moderate market uptake, bolstered by the success of other anti-VEGF agents like bevacizumab. However, sales plateaued due to:

• Limited indications: ZALTRAP’s approval is restricted mainly to mCRC, reducing its broader market potential.
• Competitive alternatives: Bevacizumab, ramucirumab, and newer agents with improved safety profiles and broader indications captured significant market share.
• Generic and biosimilar threats: As patent protections mature, biosimilars are entering the market, exerting downward pressure on pricing and sales.

According to recent earnings reports and market intelligence, ZALTRAP's annual sales have declined steadily, with estimates hovering around $50-100 million globally, primarily in the U.S. and Europe [4].

Competitive Landscape

The anti-angiogenic market is highly competitive, dominated by:

• Bevacizumab (Avastin): The pioneer in VEGF inhibition, with extensive indications and patent protections.
• Ramucirumab (Cyramza): Approved for gastric, colorectal, and lung cancers; positioned as a direct competitor.
• Apatinib and other small-molecule inhibitors: Offering oral administration with promising efficacy signals.

ZALTRAP's niche remains in mCRC post-failure of prior therapies, but the rapid evolution of immuno-oncology and targeted therapies limits its growth prospects.

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Market Projection and Future Outlook

Factors Influencing Future Growth

1. Regulatory Approvals and Expansions:
   The potential approval of ZALTRAP in other indications could revitalize its market position. However, current clinical trial data do not robustly support expansion beyond mCRC.

2. Pipeline Development and Combination Approaches:
   Ongoing studies exploring combinations with immuno-oncology agents may enhance efficacy, attracting regulatory interest for new indications or label extensions.

3. Competitive Dynamics:
   The emergence of more targeted therapies and biologics with better safety and efficacy profiles continues to challenge ZALTRAP’s market share.

4. Pricing and Reimbursement:
   Price sensitivity, especially amidst biosimilar competition, could further limit sales growth.

Market Forecast (2023-2030)

Given these factors, ZALTRAP’s global sales are projected to decline modestly over the next five years, stabilizing around $30-50 million annually by 2025. Without significant new indications or breakthroughs in combination therapies, its role will likely remain niche, confined primarily to specific mCRC patient subsets.

In emerging markets and regions with limited access to new biologics, ZALTRAP may sustain marginal popularity. Conversely, in North America and Europe, the outlook is more cautious, with sales likely diminishing further due to competitive pressures.

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Conclusion: Strategic Considerations

While ZALTRAP remains a viable therapeutic option in metastatic colorectal cancer, its clinical and market trajectories are constrained by competition and limited broadening of indications. Developers and investors should monitor ongoing trials for potential breakthroughs in combination strategies and label expansions. Cost-effective biosimilars and shifting treatment paradigms emphasize the need for continuous innovation to sustain ZALTRAP’s relevance in the evolving oncology landscape.

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Key Takeaways

• Clinical stagnation: ZALTRAP’s clinical development has been largely stagnant post-approval, with limited new trials or indications being explored.
• Market saturation: Competitive biologics and biosimilars significantly diminish ZALTRAP’s market share and sales potential.
• Future prospects: Growth hinges on successful combination therapies and regulatory expansion, which are currently uncertain.
• Strategic positioning: Market players should evaluate the drug’s niche applications and pipeline developments to inform investment and development decisions.
• Industry outlook: The anti-angiogenic market faces continued disruption from immunotherapies and targeted agents, pressuring older biologics like ZALTRAP.

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FAQs

1. Is ZALTRAP still being actively developed for new indications?
No, most development efforts have been limited, with ongoing studies primarily focusing on combination therapies in existing indications.

2. How does ZALTRAP compare to other VEGF inhibitors like bevacizumab?
ZALTRAP's efficacy in mCRC is comparable but less established than bevacizumab, which has broader indications and a more extensive clinical history.

3. What are the main safety concerns associated with ZALTRAP?
Hypertension, bleeding, thromboembolic events, and proteinuria are common adverse effects leading to cautious use.

4. Are biosimilars available for ZALTRAP?
Currently, no biosimilars for ZALTRAP are on the market; however, biosimilar VEGF inhibitors exist, intensifying price competition.

5. What is the outlook for ZALTRAP’s role in future oncology treatments?
Its future depends on successful combination strategies and regulatory approvals for expanded indications. Without significant breakthroughs, its role will likely diminish.

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References

1. Van Cutsem E, et al. (2012). "Rationale and design of the VELOUR trial." Journal of Clinical Oncology.
2. ClinicalTrials.gov. Multiple studies involving ziv-aflibercept combinations. Available at: clinicaltrials.gov.
3. Smith JD, et al. (2020). "Emerging combination therapies involving anti-VEGF agents." Oncology Reports.
4. FiercePharma. (2023). "ZALTRAP sales report & market analysis." FiercePharma.

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This analysis aims to furnish healthcare professionals and industry stakeholders with comprehensive insights into ZALTRAP’s clinical and market outlook, fostering strategic decision-making based on the latest data.