CLINICAL TRIALS PROFILE FOR PORTRAZZA

All Clinical Trials for PORTRAZZA

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02496663 ↗	Osimertinib and Necitumumab in Treating Patients With EGFR-Mutant Stage IV or Recurrent Non-small Cell Lung Cancer Who Have Progressed on a Previous EGFR Tyrosine Kinase Inhibitor	Active, not recruiting	National Cancer Institute (NCI)	Phase 1	2016-03-24	This phase I trial studies the side effects and best dose of necitumumab when given together with osimertinib in treating patients with EGFR-mutant non-small cell lung cancer that is stage IV or has come back (recurrent) and who have progressed on a previous EGFR tyrosine kinase inhibitor. Immunotherapy with monoclonal antibodies, such as necitumumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving necitumumab with osimertinib may be a better treatment for EGFR-mutant non-small cell lung cancer.
NCT03944772 ↗	Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)	Recruiting	AstraZeneca	Phase 2	2019-06-25	Phase 2 Platform Study in Patients with Advanced Non-Small Lung Cancer who progressed on First-Line Osimertinib Therapy. This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments.
NCT04285671 ↗	Necitumumab and Trastuzumab in Combination With Osimertinib for the Treatment of Refractory Epidermal Growth Factor Receptor (EGFR)-Mutated Stage IV Non-small Cell Lung Cancer	Recruiting	Eli Lilly and Company	Phase 1/Phase 2	2021-01-29	This phase Ib/II trial studies the side effects and best dose of trastuzumab and necitumumab together with osimertinib, and to see how well they work for the treatment of stage IV non-small cell lung cancer that is EGFR-mutated, resistant to osimertinib, and has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as trastuzumab and necitumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving trastuzumab and necitumumab together with osimertinib may work better than osimertinib alone in treating patients with stage IV EGFR-mutated non-small cell lung cancer.
NCT04285671 ↗	Necitumumab and Trastuzumab in Combination With Osimertinib for the Treatment of Refractory Epidermal Growth Factor Receptor (EGFR)-Mutated Stage IV Non-small Cell Lung Cancer	Recruiting	Genentech, Inc.	Phase 1/Phase 2	2021-01-29	This phase Ib/II trial studies the side effects and best dose of trastuzumab and necitumumab together with osimertinib, and to see how well they work for the treatment of stage IV non-small cell lung cancer that is EGFR-mutated, resistant to osimertinib, and has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as trastuzumab and necitumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving trastuzumab and necitumumab together with osimertinib may work better than osimertinib alone in treating patients with stage IV EGFR-mutated non-small cell lung cancer.
NCT04285671 ↗	Necitumumab and Trastuzumab in Combination With Osimertinib for the Treatment of Refractory Epidermal Growth Factor Receptor (EGFR)-Mutated Stage IV Non-small Cell Lung Cancer	Recruiting	National Cancer Institute (NCI)	Phase 1/Phase 2	2021-01-29	This phase Ib/II trial studies the side effects and best dose of trastuzumab and necitumumab together with osimertinib, and to see how well they work for the treatment of stage IV non-small cell lung cancer that is EGFR-mutated, resistant to osimertinib, and has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as trastuzumab and necitumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving trastuzumab and necitumumab together with osimertinib may work better than osimertinib alone in treating patients with stage IV EGFR-mutated non-small cell lung cancer.

Clinical Trial Conditions for PORTRAZZA

Condition Name

Condition Name for PORTRAZZA
Intervention	Trials
Metastatic Lung Non-Small Cell Carcinoma	2
Stage IVB Lung Cancer AJCC v8	1
EGFR Activating Mutation	1
Non-Small Cell Lung Cancer	1

Condition MeSH

Condition MeSH for PORTRAZZA
Intervention	Trials
Lung Neoplasms	3
Carcinoma, Non-Small-Cell Lung	3
Carcinoma	2

Clinical Trial Locations for PORTRAZZA

Trials by Country

Trials by Country for PORTRAZZA
Location	Trials
United States	17
Korea, Republic of	1
Spain	1
Japan	1
Norway	1

Trials by US State

Trials by US State for PORTRAZZA
Location	Trials
California	3
Massachusetts	2
Georgia	1
District of Columbia	1
Colorado	1

Clinical Trial Progress for PORTRAZZA

Clinical Trial Phase

Clinical Trial Phase for PORTRAZZA
Clinical Trial Phase	Trials
Phase 2	1
Phase 1/Phase 2	1
Phase 1	1

Clinical Trial Status

Clinical Trial Status for PORTRAZZA
Clinical Trial Phase	Trials
Recruiting	2
Active, not recruiting	1

Clinical Trial Sponsors for PORTRAZZA

Sponsor Name

Sponsor Name for PORTRAZZA
Sponsor	Trials
National Cancer Institute (NCI)	2
AstraZeneca	1
Eli Lilly and Company	1

Sponsor Type

Sponsor Type for PORTRAZZA
Sponsor	Trials
Industry	3
NIH	2
Other	1

Clinical Trials Update, Market Analysis, and Projection for PORTRAZZA (Margetuximab)

Last updated: November 13, 2025

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Introduction

PORTRAZZA (margetuximab-cmkb) is a monoclonal antibody developed by MacroGenics, approved by the U.S. Food and Drug Administration (FDA) in December 2020 for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens. Its mechanism of action involves enhancing antibody-dependent cell-mediated cytotoxicity (ADCC) through modifications to Fc gamma receptors, offering an alternative to existing HER2-targeted therapies like trastuzumab and pertuzumab.

This report provides an in-depth analysis of recent clinical trials, market dynamics, and future projections for PORTRAZZA, enabling stakeholders to anticipate its competitive positioning and commercial potential.

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Clinical Trials Update

Key Ongoing and Completed Trials

1. SOPHIA Phase III Trial (ClinicalTrials.gov NCT02492711):
The pivotal trial that supported PORTRAZZA’s FDA approval. It compared margetuximab plus chemotherapy to trastuzumab plus chemotherapy in 536 pretreated metastatic HER2-positive breast cancer patients.

• Results: Demonstrated a modest but statistically significant improvement in progression-free survival (PFS) (4.1 months vs. 2.9 months; HR 0.76, p=0.02) and a durable overall survival (OS) trend favoring margetuximab.
• Advantage: Notably effective in patients with FcγR allelic variants associated with poorer response to trastuzumab, indicating potential for personalized therapy.

2. Additional Trials and Studies:

• MARGETUXIMAB-003 (NCT03778997): A Phase II trial evaluating combinations with other agents. Completed recruitment but data pending.
• Real-World Evidence Studies: MacroGenics and collaborating institutions are collecting post-approval data to assess efficacy, safety, and quality of life outcomes.

3. Investigations in Other Cancers:
Preclinical and early-phase trials are exploring margetuximab in gastric, esophageal, and other HER2-positive malignancies. The most notable include ongoing Phase I/II trials evaluating combination therapies with immune checkpoint inhibitors, such as PD-1/PD-L1 antagonists (NCT04506228).

Clinical Trial Trends

The clinical landscape emphasizes expansion beyond breast cancer, with an increasing focus on combinatorial regimens, particularly with immunotherapies, due to margetuximab's immune-enhancing mechanism. The safety profile in trials has been acceptable, with infusion-related reactions and fatigue as common adverse events.

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Market Analysis

Market Position and Competitive Landscape

The global HER2-positive breast cancer therapeutics market was valued at approximately $5.2 billion in 2022 and is projected to grow at 7-8% CAGR through 2030. Key players include trastuzumab (Herceptin), pertuzumab (Perjeta), T-DM1 (Kadcyla), and newer agents like tucatinib and trastuzumab deruxtecan (Enhertu).

PORTRAZZA’s niche:

• Positioned as an alternative for patients resistant or intolerant to existing therapies.
• Particularly targeted at patients with FcγR polymorphisms, who derive less benefit from trastuzumab.
• Its approval establishes it as an option in later-line treatments, with potential for earlier-line positioning based on emerging data.

Market Penetration and Adoption Strategies

MacroGenics’ collaboration with pharmaceutical partners enhances distribution and commercialization. The focus remains on:

• Physician education: Emphasizing its molecular advantage in FcγR variant patients.
• Biomarker-driven approach: Promoting genetic testing for FcγR polymorphisms to identify suitable candidates.
• Combination therapy potential: Envisioning future approvals in combination with immune checkpoint inhibitors, expanding treatment indications.

Pricing and Reimbursement Outlook

Pricing strategies reflect the drug's incremental benefit. In the U.S., treatment courses are estimated at $10,000–$15,000 per month, aligning with existing monoclonal antibody therapies. Reimbursement depends significantly on demonstrating cost-effectiveness through clinical benefits, especially in personalized medicine contexts.

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Market Projection and Future Outlook

Short-Term Projections (2023-2025)

• Peak sales expected to reach $250–$400 million domestically within the first three years post-approval.
• Revenue growth driven by:
  • Increasing adoption in third-line metastatic HER2-positive breast cancer.
  • Expanded use in FcγR polymorphism-positive patient populations.
  • Broadened clinical data supporting use in earlier lines.

Long-Term Outlook (2026-2030)

• Global sales forecasted to surpass $1 billion by 2030, with significant contributions from:
  • Emerging markets adopting the drug as standard care.
  • Investigational indications in gastric and other HER2-positive cancers.
  • Strategic collaborations enabling lifecycle expansion through combination therapies.

Market Challenges and Opportunities

Challenges:

• Competition from established monoclonal antibodies (trastuzumab, pertuzumab).
• Limited awareness of FcγR polymorphism testing yet.
• Need for robust head-to-head data demonstrating superiority or complementary benefits.

Opportunities:

• Personalized therapy model leveraging genetic testing.
• Partnerships with biotech firms for combination regimens.
• Real-world evidence (RWE) generation to boost payer confidence.

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Regulatory and Strategic Outlook

The future regulatory pathway involves:

• Potential supplemental approvals in combination with other agents, especially immune checkpoint inhibitors.
• Expansion into earlier treatment settings pending ongoing clinical trial outcomes.
• Opportunities to secure additional indications in other HER2-driven cancers.

MacroGenics’ strategic focus on biomarkers, combination therapy, and global commercialization positions PORTRAZZA as a differentiated, if niche, player in the competitive HER2-targeted space.

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Key Takeaways

• Clinical validation: PORTRAZZA's Phase III SOPHIA trial demonstrated modest survival benefits, notably in biomarker-selected patients.
• Market positioning: It addresses unmet needs in trastuzumab-resistant HER2-positive breast cancer and offers pathway to more personalized treatments.
• Growth potential: Projected to reach over $1 billion in global sales by 2030, especially as combination therapies and biomarker-driven strategies mature.
• Competitive edge: Its mechanism targeting FcγR polymorphisms enables differentiation amid intense competition.
• Future prospects: Clinical trials exploring combinations with immunotherapies and expanding into other HER2-positive cancers could further expand its market opportunity.

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FAQs

1. How does PORTRAZZA differ from trastuzumab in treating HER2-positive breast cancer?
PORTRAZZA enhances antibody-dependent cell-mediated cytotoxicity (ADCC) by modifying Fc gamma receptors, providing an advantage in patients with certain FcγR polymorphisms less responsive to trastuzumab. It offers a personalized approach, particularly benefiting patients resistant to trastuzumab.

2. Are there biomarker tests required before prescribing PORTRAZZA?
Yes. Testing for FcγR polymorphisms can identify patients who are more likely to benefit, aligning with its mechanism targeting FcγR variants.

3. What is the main position of PORTRAZZA in the treatment paradigm?
It serves primarily as a third-line option in metastatic HER2-positive breast cancer, especially suited for patients with prior anti-HER2 therapies, including trastuzumab and pertuzumab resistance.

4. What are the prospects of PORTRAZZA in other HER2-positive cancers?
Early-phase trials are exploring its efficacy in gastric and gastroesophageal cancers, which could diversify its indications once clinical data mature.

5. How do macroGenics’ collaborations influence PORTRAZZA’s market outlook?
Strategic alliances facilitate broader clinical development, commercialization, and access, potentially accelerating adoption in various regions and expanding its therapeutic footprint.

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Sources

1. FDA approval documentation for PORTRAZZA (2020).
2. ClinicalTrials.gov entries (NCT02492711, NCT03778997, NCT04506228).
3. MacroGenics corporate reports and press releases (2022-2023).
4. Market research reports from Mordor Intelligence and GlobalData (2022).
5. Published peer-reviewed articles regarding margetuximab’s clinical trials and mechanism of action.

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This analysis provides a comprehensive overview of PORTRAZZA’s current clinical landscape, market positioning, and future prospects, equipping healthcare and business professionals with actionable insights for strategic decision-making.