Illustration of a tumor fortress being breached by immune cells, symbolizing targeted cancer therapy.

Targeting Cancer's Shields: A New Fusion Protein Tackles Esophageal Adenocarcinoma

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Mira Elwood in Health & Wellness December 2025 • 5 min read.

"Early trial results show promise for M7824, a bifunctional protein that blocks PD-L1 and TGF-β, offering new hope for patients with advanced esophageal cancer."


Esophageal adenocarcinoma (EAC) remains a formidable challenge, often diagnosed at advanced stages where treatment options are limited. The current standard of care, typically based on gastric cancer guidelines, provides modest success, highlighting the urgent need for innovative therapeutic strategies.

One promising avenue lies in harnessing the power of immunotherapy. Cancer cells often employ tactics to suppress the immune system, allowing them to grow unchecked. Two key players in this suppression are TGF-β and PD-L1. TGF-β contributes to the tumor microenvironment, fostering an environment conducive to cancer survival, while PD-L1 acts as a shield, preventing immune cells from recognizing and attacking the tumor.

M7824 (also known as MSB0011359C) represents a novel approach to cancer treatment. It's a bifunctional fusion protein, meaning it combines two distinct functions into a single molecule. One part of M7824 is an antibody that specifically targets and blocks PD-L1. The other part consists of two extracellular domains of the TGF-β receptor II (TGF-βRII), effectively acting as a 'trap' to neutralize TGF-β. By simultaneously targeting these two pathways, M7824 aims to dismantle cancer's defense mechanisms and unleash the immune system to fight back.

Early Trial Results: A Glimmer of Hope for Advanced EAC

Illustration of a tumor fortress being breached by immune cells, symbolizing targeted cancer therapy.

A recent phase I clinical trial (NCT02517398) investigated the potential of M7824 in patients with advanced EAC who had progressed after platinum-based chemotherapy. This patient population often has limited treatment options, making the results of this trial particularly significant. Patients received M7824 intravenously every two weeks until their disease progressed, they experienced unacceptable toxicity, or they withdrew from the trial.

The primary goal of the trial was to assess the overall response rate (ORR), which represents the percentage of patients whose tumors shrank or disappeared in response to the treatment. Secondary endpoints included evaluating the safety and tolerability of M7824, as well as exploring potential biomarkers that could predict treatment response. Tumor samples were analyzed to determine the level of PD-L1 expression on cancer cells.

  • Manageable Safety Profile: M7824 demonstrated a manageable safety profile in this heavily pre-treated patient population. While most patients experienced treatment-related adverse events (TRAEs), the majority were mild to moderate in severity.
  • Encouraging Signs of Efficacy: The trial showed an overall response rate (ORR) of 20%, meaning that 20% of patients experienced a confirmed partial response (PR), where their tumors shrank significantly. Three patients had ongoing responses at the time of data analysis.
  • Disease Stabilization: An additional 13.3% of patients experienced stable disease (SD), meaning their tumors did not shrink but also did not grow significantly.
  • PD-L1 Expression Not Predictive: Interestingly, the response to M7824 did not appear to be dependent on the level of PD-L1 expression in the tumor. The ORR was similar in patients with PD-L1-positive and PD-L1-negative tumors.
These early results suggest that M7824 may offer a new treatment option for patients with advanced EAC, even after they have progressed on prior therapies. The manageable safety profile and encouraging signs of efficacy warrant further investigation in larger clinical trials.

Future Directions: Unlocking the Full Potential of M7824

While these preliminary findings are promising, further research is needed to fully understand the potential of M7824 in the treatment of EAC. Ongoing and future clinical trials will evaluate the efficacy of M7824 in larger patient populations and in combination with other therapies. Biomarker analysis will also play a crucial role in identifying patients who are most likely to benefit from this novel treatment approach. By continuing to explore the mechanisms of action and identify predictive biomarkers, researchers hope to unlock the full potential of M7824 and improve outcomes for patients with this challenging disease.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

1

What exactly is M7824 and how does it work?

M7824 is a novel bifunctional fusion protein designed to simultaneously target two mechanisms that cancer cells use to evade the immune system: PD-L1 and TGF-β. One part of M7824 is an antibody that blocks PD-L1, preventing it from shielding the tumor from immune cells. The other part acts as a 'trap' for TGF-β, neutralizing its immunosuppressive effects in the tumor microenvironment. This dual action aims to dismantle cancer's defenses and allow the immune system to attack the tumor.

2

What is esophageal adenocarcinoma, and why is M7824 being studied for this type of cancer?

Esophageal adenocarcinoma (EAC) is a type of cancer that occurs in the esophagus. It's often diagnosed at advanced stages, making treatment challenging. The current standard treatments have limited success, highlighting the need for new therapeutic strategies. M7824 is being investigated as a potential new treatment option for advanced EAC, particularly for patients who have progressed after prior therapies like platinum-based chemotherapy. Other cancers may benefit from similar therapies; however, this is still investigational.

3

What is PD-L1, and why is blocking it considered important in cancer treatment?

PD-L1 is a protein that cancer cells use to shield themselves from the immune system. It binds to receptors on immune cells, preventing them from recognizing and attacking the tumor. Blocking PD-L1 is important because it removes this 'shield,' allowing immune cells to target and destroy cancer cells. However, clinical trials showed that response to M7824 was not dependent on PD-L1 expression.

4

What is TGF-β, and how does it affect cancer development and the immune system?

TGF-β contributes to the tumor microenvironment by creating conditions that favor cancer cell survival and suppress the immune system. It promotes the growth of blood vessels that feed the tumor and inhibits the activity of immune cells that could attack it. Neutralizing TGF-β is important because it disrupts this supportive environment and allows the immune system to function more effectively. M7824 is designed to neutralize TGF-β to hinder EAC growth. Other agents that block TGF-β are currently being studied in various cancers.

5

What were the main findings from the clinical trial that tested M7824?

A clinical trial of M7824 in patients with advanced EAC showed a manageable safety profile and encouraging signs of efficacy. Approximately 20% of patients experienced a confirmed partial response, meaning their tumors shrank significantly. An additional 13.3% of patients experienced stable disease, meaning their tumors did not grow significantly. While promising, these are early results, and further research is needed to fully understand the potential of M7824.

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