Summit Therapeutics Unveils Breakthrough Lung Cancer Drug Data

Summit Therapeutics Unveils Groundbreaking Lung Cancer Treatment Data at World Conference on Lung Cancer

Summit Therapeutics caught the attention of the World Conference on Lung Cancer in San Diego as it revealed Phase III data from its HARMONi-2 study, creating waves with its groundbreaking lung cancer treatment, ivonescimab. The study, conducted in China, encompassed 398 patients with PD-L1-positive, advanced non-small cell lung cancer (NSCLC). The most significant revelation was that Summit’s ivonescimab slashed the risk of cancer progression or death by nearly half in comparison to MSD’s Keytruda. Patients using ivonescimab experienced a median progression-free survival (PFS) of over 11 months, significantly outstripping the six months PFS for those on Keytruda. This compelling 5.3-month disparity translated to a 49% reduction in risk, an outcome of notable statistical significance that could potentially revolutionize the NSCLC treatment landscape.

In May 2024, Summit had initially announced the trial's success, triggering a dramatic surge in its stock price. With detailed data now available, Summit's market cap stands at a substantial $13.55 billion. This achievement is exceptionally noteworthy, as no other Phase III NSCLC trial has demonstrated such a substantial PFS improvement against Keytruda, a lucrative drug that raked in $25 billion last year and is anticipated to reach $33.7 billion by 2028.

Summit acquired ivonescimab in 2022 for $500 million from Akeso, securing rights in the US and Europe. If approved, ivonescimab's sales could reach up to $1.7 billion by 2030. Nevertheless, the study did raise concerns regarding higher rates of severe side effects with ivonescimab in comparison to Keytruda. The incidence of Grade 3 or above treatment-related adverse events (TRAEs) stood at 29.4% for ivonescimab, while it was 15.6% for Keytruda. Despite this, Summit has plans to launch a Phase III trial in early 2025 to further evaluate ivonescimab's efficacy in high PD-L1 expression metastatic NSCLC patients.

Summit's CEO, Robert Duggan, described the results as a "historic moment" and hinted at the possibility of a radical shift in cancer treatment options. Indeed, this data could mark a turning point in the management of advanced NSCLC, offering patients a new, potentially more effective treatment choice.

Key Takeaways

• Ivonescimab reduced lung cancer progression risk by 49% compared to Keytruda in Phase III HARMONi-2 study.
• The study showed a 5.3-month increase in progression-free survival for ivonescimab versus Keytruda.
• HARMONi-2 involved 398 Chinese patients with PD-L1-positive, advanced non-small cell lung cancer.
• Summit plans to initiate Phase III HARMONi-7 trial in early 2025 to further compare ivonescimab and Keytruda.
• Ivonescimab reported higher rates of severe side effects, with 29.4% Grade 3 or above TRAEs versus 15.6% for Keytruda.

Analysis

Summit Therapeutics' success with ivonescimab could potentially disrupt the NSCLC treatment market, significantly impacting MSD's Keytruda sales and market share. The remarkable 49% reduction in progression risk positions ivonescimab as a robust competitor, potentially attracting investment and partnership interest. However, the higher incidence of side effects might restrict uptake, prompting the necessity for further trials. In the short term, Summit's stock and market cap are expected to surge, while in the long term, regulatory approval and market penetration will determine ivonescimab's impact. The significant role of China in this study underscores its growing influence in global clinical trials.

Did You Know?

- **PD-L1-positive, advanced non-small cell lung cancer (NSCLC)**:
  - **PD-L1**: Programmed Death-Ligand 1, a protein found on the surface of some cancer cells that interacts with PD-1 receptors on immune cells, inhibiting the immune response and allowing cancer cells to evade detection.
  - **NSCLC**: Non-small cell lung cancer, the most common type of lung cancer, accounting for about 85% of all lung cancer cases. It is typically less aggressive than small cell lung cancer but still requires advanced treatment options.
  - **PD-L1-positive, advanced NSCLC**: Refers to cases of NSCLC where the cancer cells express PD-L1, making them particularly responsive to treatments that target this pathway, such as immunotherapies like Keytruda and ivonescimab.

- **Progression-free survival (PFS)**:
  - **PFS**: A measure of the time during and after treatment during which a patient lives with a disease but it does not get worse. In oncology, it is a critical endpoint in clinical trials as it indicates how long patients live without their cancer progressing.
  - **Statistical significance**: In the context of clinical trials, it means that the observed difference in PFS between treatment groups (e.g., ivonescimab vs. Keytruda) is unlikely to have occurred by chance and is likely a true effect of the treatment.

- **Grade 3 or above treatment-related adverse events (TRAEs)**:
  - **Grade 3 or above TRAEs**: A classification system used to describe the severity of adverse events (side effects) caused by medical treatments. Grade 3 indicates severe or medically significant but not immediately life-threatening events, while Grade 4 indicates life-threatening consequences.
  - **TRAEs**: Adverse events that are directly related to the treatment being administered, as opposed to the underlying disease or other factors. In the context of ivonescimab, higher rates of Grade 3 or above TRAEs suggest that while the drug is effective, it may also cause more severe side effects compared to Keytruda.