Key Insights from SITC 2024

Keya Watkins

November 25, 2024

Overcoming Cancer Resistance to Immunotherapy

The Society for Immunotherapy of Cancer (SITC) is the premier conference dedicated to the advancement of immunology and immunotherapy treatments. Taking place in Houston, Texas, this year’s event had more than 6,000 representatives from academia, government and industry in attendance. Nearly 1,500 cutting-edge oral and poster abstracts were presented during the conference.

Progress in cell therapy research

As we look to the future of immunotherapy research, delegates at this year’s SITC conference paused to reflect on the last decade plus of progress.

Beginning with the US Food and Drug Administration’s (FDA’s) approval in 2011 of ipilimumab for advanced melanoma, immunotherapy, and specifically immune checkpoint inhibitors, have experienced much success. Yet despite these successes, particularly in melanoma and metastatic non-small cell lung cancer (NSCLC), challenges and limitations persist. For example, less than half of melanoma patients treated with checkpoint inhibitors respond to immunotherapy. Additionally, some cancer types, such as pancreatic or prostate, are highly resistant to immunotherapy treatment, showing little to no response at all.

Resistance and varied response to immunotherapy

Conference delegates hotly debated the leading reasons for cancer resistance or varying responses to immunotherapy treatment, including:

Addressing T cell exhaustion: T cell exhaustion is a phenomenon that occurs when T cells lose their ability to kill cancer cells because of overstimulation of the immune system. Researchers are exploring ways to restore T cell function and, ultimately, the effectiveness of checkpoint inhibitors.³
Tumor heterogeneity: Antigen expression can vary widely within a single tumor, across different tumors in the same patient or across patients, greatly impacting overall immunotherapy response. Drug developers are looking at ways to overcome tumor heterogeneity and enhance responsiveness to immunotherapy treatments.⁴

The converging of technology and science

The rapid integration of technology with science in drug development was yet another big theme at this year’s conference. This powerful combination is radically transforming our understanding of disease and the development of new treatments. The following are just a few of the areas that were being discussed.

Next-generation sequencing

Next-generation sequencing (NGS), a technology that allows for rapid sequencing of DNA and RNA, is enabling researchers to analyze genetic material at scales and speed never seen before. Our growing understanding of disease mechanism at the molecular level will enable us to develop more targeted, effective cancer therapies in less time.

Assays to detect specific biomarkers

Biomarkers provide insight into the characteristics of a patient’s tumor, thereby enabling us to develop more personalized, effective treatments. Immunohistochemistry has been a widely used assay to date but researchers are still searching for more precise measurements. Some of the new promising techniques being discussed include multiplex immunofluorescence (mIF), CODEX, single-cell RNA sequencing and gene expression profiling.

Biomarkers designed for early detection to guide immunotherapy response

Researchers are diligently exploring the development of new biomarkers for earlier detection, as they can help guide immunotherapy response and identify which patients will benefit most from treatment.

Machine learning and artificial intelligence

There was a tremendous buzz around the use of machine learning (ML) and artificial intelligence (AI) to facilitate the development of new immunotherapies. Experts believe that leveraging the power of ML and AI will allow us to streamline research and more accurately predict and optimize cancer patients’ responses to immunotherapy.

Innovative, breakthrough poster presentations

The latest breakthroughs and significant research findings in immunotherapy are always exciting to hear about at SITC. These were two of the most notable poster presentations I attended:

First-in-class T cell receptor chain in patients with antigen-rich solid tumors resistant to anti-PD-L1

Researchers with Gustave Roussy, a top-ranked cancer treatment center in France, and other institutions published an impressive poster focused on START001, a phase I/II trial of invikafusp alfa, a first-in-class T cell receptor (TCR) β chain-targeted bispecific antibody, as a monotherapy in patients with antigen-rich solid tumors resistant to anti-PD-L1. This research is significant because the development of a new T cell receptor chain could help overcome resistance and improve the immune system’s ability to recognize and attack these tumors.

IGNYTE trial findings in patients with anti-PD-1 failed melanoma

The University of Texas MD Anderson Cancer Center presented an oral analysis focusing on the registration-intended cohort of patients in the IGNYTE trial with anti-PD-1 failed melanoma. The study included a clinical subgroup analysis and initial biomarker data for this subpopulation. This research is crucial to better understand which patients benefit the most from immunotherapy and how to improve outcomes for patients who have limited options after failing standard immunotherapy.

SITC offered a great opportunity to celebrate the successes and rally around the challenges that persist in immunotherapy research. Immunotherapy continues to lead the way as an innovative, next-generation treatment for cancer patients.

We can help

With our exclusive biotech focus and next-gen oncology experience, Catalyst Oncology supports early- to late-phase drug development across a range of both solid and hematologic indications. Greater than 41% of our active trial portfolio is in immuno-oncology (IO). Connect with us to learn more about our IO expertise and discover how we can support your IO trial.