#United States #Cambridge #CREATE Medicines #HCC Trial #MT-303

Introduction

CREATE Medicines Inc., a clinical-stage biotechnology company, has taken a significant step in cancer treatment by administering the first dose of MT-303 in its innovative clinical trial aimed at advanced hepatocellular carcinoma (HCC). This therapy utilizes an in vivo CAR approach combined with established immunotherapy, promising potentially transformative outcomes for patients suffering from this challenging liver cancer.

The Breakthrough Trial

On December 9, 2025, CREATE announced that it successfully dosed the first patient in its frontline HCC clinical trial. This study evaluates the effectiveness of MT-303, which is an investigational therapy designed to target the glypican-3 (GPC3) protein found predominantly in HCC cells. Delivered via CREATE's proprietary mRNA-LNP platform, MT-303 seeks to engage the body’s immune system against cancer cells effectively. The trial combines MT-303 with atezolizumab and bevacizumab, two validated medications that represent the current standard of care for patients newly diagnosed with metastatic HCC.

Understanding MT-303

MT-303 is noteworthy for its approach that programs immune cells directly within the body, a novel method that differentiates it from traditional therapies. This therapy has demonstrated a safe and well-tolerated profile in previous studies, making it an ideal candidate to be investigated in combination with other therapies. The performance of MT-303 in terms of engaging the immune system and eliciting responses against tumor cells has been substantiated through clinical data, where over 40 patients have shown promising results, including CAR expression and immune cell activation.

Clinical Significance

The trial holds particular significance because it targets treatment-naïve patients, which means they have not yet undergone systemic therapy. In this context, the immune system’s inherent fitness is preserved, increasing the likelihood of achieving substantial, lasting effects. Dr. Matthew Maurer, the Chief Medical Officer at CREATE Medicines, emphasized the trial's potential, stating, "Advancing MT-303 into a frontline combination study represents an important evolution for the in vivo CAR field."

Addressing a Critical Need

Currently, liver cancer is among the rapidly rising global cancer threats, with more than 850,000 new diagnoses each year. Hepatocellular carcinoma, the most common form of primary liver cancer, frequently occurs in individuals with underlying health issues like chronic liver disease or viral hepatitis. While advancements in medical technology have provided some therapeutic options, long-term outcomes remain disappointingly low for many patients, particularly once first-line treatments fail.

The need for innovative therapies that can offer significant, sustained immune responses is pressing. Dr. Vladimir Andelkovic, a principal investigator at ICON Cancer Centre in Brisbane, highlighted the vital need for new modalities like MT-303 to enhance existing treatment regimens.

Conclusion

CREATE Medicines's commitment to advancing MT-303 embodies the spirit of innovation required to tackle one of the most formidable cancers. As the trial progresses, the data collected will not only inform the efficacy and safety profiles of MT-303 but will also pave the way for future treatment strategies in overcoming the limitations imposed by current therapies. The healthcare community watches in anticipation for the profound changes MT-303 may bring to patients battling HCC and brings hope for improved outcomes in the near future.

For more information about CREATE Medicines and its groundbreaking work in the oncology space, visit their official website: createmedicines.com.