AACR Annual Meeting 2024

SHOWCASING TECHNOLOGICAL ADVANCES

The AACR Annual Meeting has always been a showcase for emerging technologies, with an increasing emphasis in recent years on data science, artificial intelligence, and computational biology. However, while developing the 2024 program, Annual Meeting Program Cochairs Keith T. Flaherty, MD, FAACR, and Christina Curtis, PhD, noted that these technologies have reached an inflection point, where a vast compendium of molecular information has been generated that can be used to better diagnose patients, to better stratify them, and to better identify the therapies that may benefit them.

The program for the AACR Annual Meeting 2024 highlighted this technological tipping point in two different ways:

• Several scientific sessions—including the Opening Plenary Session—integrated technology by pairing presentations on discoveries in basic, translational, and clinical science with presentations on the tools that support and amplify those discoveries.
• The program included an expanded number of technology-focused sessions—including the launch of a new Advances in Technology session type, which featured topics such as functional precision genomics, harnessing computational oncology for biological insight, and new approaches to liquid biopsies. The program also featured a Plenary Session chaired by Vivek Subbiah, MD, dedicated to “Artificial Intelligence at the Interface: Accelerating Evidence Generation, Advancing Disparities Research, and Improving Trial Design.”

HIGH-IMPACT CLINICAL TRIALS

Under the leadership of the AACR Annual Meeting Clinical Trials Committee—led by Cochairs Shivaani Kummar, MD, and Ryan B. Corcoran, MD, PhD—the AACR Annual Meeting continued to serve as a premier presentation venue for practice-changing clinical trials. More than 240 clinical trials—including 24 Phase III studies—were presented during the meeting, 37 of which were showcased in oral plenary session and minisymposium presentations.

The clinical trial plenary sessions highlighted a wide range of treatment approaches, including novel immunotherapy strategies, immune checkpoint inhibitor combinations, and advances in targeted therapies. An additional plenary session featured trials that explored the use of biomarkers to identify subgroups of patients who may respond best to novel combination therapies.

These clinical trial presentations outlined critical advances in cancer care across a range of treatment options and cancer types:

• COMPASSION-15 Trial: Cadonilimab Plus Chemotherapy Improves Survival in Gastric Cancer Patients Regardless of PD-L1 Status. Immune checkpoint inhibitors (ICIs) are approved by the U.S. FDA for the first-line treatment of gastric and gastroesophageal junction (G/GEJ) cancers that do not express HER2. However, while ICIs are most effective in patients whose tumors express high levels of PD-L1, treatment options are limited for patients whose tumors have low PD-L1 expression. Early-phase clinical trials demonstrated that the PD-1/CTLA-4 bispecific antibody cadonilimab plus chemotherapy showed benefit for G/GEJ cancer patients regardless of PD-L1 expression.

  Building on these studies, Jiafu Ji, MD, PhD, presented interim results from the phase III COMPASSION-15 trial, which evaluated the efficacy and safety of cadonilimab plus chemotherapy versus placebo plus chemotherapy for the first-line treatment of G/GEJ adenocarcinoma with low PD-L1 expression. Dr. Ji reported that patients in the cadonilimab arm of the trial had a median overall survival of 15 months, compared with 10.8 months in the placebo arm. Overall response rate was 65.2% with a median response duration of 8.8 months in the cadonilimab arm and 48.9% with a median response duration of 4.4 months in the placebo arm.

  If they hold up in follow-up studies, these results indicate that cadonilimab combined with chemotherapy could become a new standard of care in first-line treatment of gastric cancer, regardless of the tumor’s PD-L1 status.

• KRYSTAL-1 Trial: Adagrasib Plus Cetuximab in KRAS^G12C-Mutated Metastatic Colorectal Cancer. KRAS^G12C mutations occur in around 4% of colorectal cancers (CRCs) and are associated with a poor prognosis. Drugs targeting KRAS^G12C, such as adagrasib, were previously only approved by the FDA to treat non-small cell lung cancer. Citing the need for more effective late-line regimens for metastatic CRC, Scott Kopetz, MD, PhD, presented efficacy and safety data from the phase I/II KRYSTAL-1 trial, which evaluated adagrasib in combination with the EGFR inhibitor cetuximab in patients with KRAS^G12C-mutated, heavily pretreated, metastatic CRC. The results were also published simultaneously in the AACR journal Cancer Discovery.

  Dr. Kopetz reported that adagrasib plus cetuximab demonstrated clinically meaningful antitumor activity, with an objective response rate of 34% and a disease control rate of 85.1%. Median progression-free survival was 6.9 months, and the median overall survival was 15.9 months. Dr. Kopetz noted that the combination was under priority review by the FDA, and it has since received an accelerated approval for this indication. Dr. Kopetz and his colleagues are further exploring the efficacy of the regimen in a phase III trial.

  Read the original study published in Cancer Discovery

  

  Read a summary of the FDA Approval of adagrasib plus cetuximab on the AACR website

  

• PETRA Trial: Next-generation PARP Inhibitor Saruparib Demonstrates Clinical Benefit in Patients with Homologous Recombination Repair (HRR)-deficient Breast Cancer. All PARP inhibitors currently approved by the FDA block both the PARP1 and PARP2 enzymes, which can limit their utility because of their higher toxicity. However, evidence has suggested that blocking PARP1 may be sufficient to prevent DNA repair in HRR-deficient tumors—and because they are less toxic, selective PARP1 inhibitors could be administered at higher doses, which could lead to improved outcomes for patients.

  Former AACR Clinical Trials Committee Chair Timothy A. Yap, MBBS, PhD, and colleagues investigated this possibility and presented the results of PETRA, a first-in-human, multicenter phase I/II clinical trial evaluating the safety, tolerability, and efficacy of the PARP1-specific inhibitor saruparib (AZD5305) in patients with previously treated HRR-deficient breast, ovarian, pancreatic, or prostate cancer. Patients in the trial had tumors with mutations in one of five HRR genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.

  Among the breast cancer patients who were treated with the recommended dose of saruparib, the objective response rate was 48.4%, the median duration of response was 7.3 months, and the median progression-free survival was 9.1 months. Dr. Yap noted that the adverse events profile from this trial compared favorably to those from trials of other PARP inhibitors and that patients maintained higher blood concentrations of saruparib at all dose levels than was typically observed with other PARP inhibitors. These results indicated that patients may be able to remain on saruparib treatment with sustained maximal target engagement and limited dose reductions or discontinuation.

• Personalized Vaccine Provides Clinical Benefit for Some Patients with Resected Head and Neck Cancers (HNSCCs). Patients with locoregional HNSCC have a high risk of disease relapse after surgery, and currently available treatments offer limited efficacy against relapsed disease. Olivier Lantz, MD, PhD, and colleagues tested the hypothesis that a personalized therapeutic vaccine tailored to a patient’s unique tumor could delay relapse of surgically resected HNSCC by triggering strong immune responses to eliminate residual disease and by making tumors more responsive to other forms of immunotherapy. They developed TG4050, an individualized vaccine that delivers 30 personalized neoantigens to induce activation and expansion of antitumor T cells. The development process featured the use of artificial intelligence and machine learning tools to analyze the genome of each patient’s tumor and identify relevant mutations and immunogenic neoantigens to create individualized vaccines.

  Dr. Lantz shared data from an ongoing phase I clinical trial evaluating the safety and efficacy of TG4050. Patients with stage 3 or 4 HPV-negative HNSCC who underwent surgery and other standard-of-care treatments were randomly assigned to receive TG4050 immediately after standard-of-care treatment (Arm A) or only upon disease relapse (Arm B). None of the Arm A patients experienced relapse after a median follow-up of 16.2 months, while three patients in Arm B experienced relapse—one after 6.2 months, another after 8.8 months, and a third after 18.5 months.

  Sixteen of the 17 vaccinated patients whose immune responses were evaluated showed evidence of activated neoantigen-specific T cells, and adverse events associated with the treatment were mild to moderate. Dr. Lantz noted that the results demonstrated the potential of individualized neoantigen-based therapeutic vaccines, and he suggested that these vaccines could become a standard of care in the future.

• Investigational RNA Vaccine for Pancreatic Cancer. Pancreatic cancer is a very deadly disease; only about 13% of pancreatic cancer patients are alive five years after diagnosis. Recent research has suggested that therapeutic cancer vaccines made from personalized neoantigens could train a patient’s immune system to recognize their pancreatic cancer cells as foreign and launch a response against them; however, these vaccines must be custom-made for each patient, which can delay treatment and negatively impact outcomes.

  Vinod Balachandran, MD, and colleagues explored the use of an mRNA platform, which enabled the rapid development of autogene cevumeran, an mRNA-based personalized cancer vaccine that targets up to 20 unique neoantigens identified from a patient’s tumor. Dr. Balachandran reported three-year follow-up data from a phase I clinical trial that evaluated the postsurgical use of autogene cevumeran combined with immune checkpoint inhibition and chemotherapy for patients with resectable pancreatic cancer.

  After a median follow-up of three years, the patients with vaccine-induced T-cell responses had significantly longer median recurrence-free survival (not reached) compared with patients who received the vaccine but had not experienced an immune response (13.4 months). According to Dr. Balachandran, the results indicated that individualized neoantigen-specific cancer vaccines can induce a robust immune response that correlates with delayed disease recurrence, which suggests that these vaccines could be an encouraging therapeutic approach for pancreatic cancer.

Read a full summary of these cancer vaccine trials on the AACR Blog, Cancer Research Catalyst

CUTTING-EDGE EDUCATIONAL PROGRAM

Under the leadership of Chair Victor E. Velculescu, MD, PhD, FAACR, the AACR Education Committee developed a comprehensive educational program for the Annual Meeting, organizing nearly 70 educational sessions and methods workshops. In addition to the long-running series on Chemistry to the Clinic and Clinical Trial Design, the educational program covered a wide range of topics, including:

• Determinants and Meanings of T Cell Recognition, Exhaustion, and Persistence
• Chemo-proteomics Approaches in Drug Discovery
• Cell Therapies for Solid Tumors
• New Targets and Mechanisms of Synthetic Lethality in Cancer Therapy
• Characterizing Complex Structural Variation and 3D Genome Architecture
• Pathology for Cancer Researchers
• Emerging Data Analysis Methods for Cancer Research

INSPIRING PLENARY SESSIONS

The highlight of the Annual Meeting program was the series of five leading-edge plenary sessions that set the tone for each day of the meeting. The central event of the meeting was the Opening Plenary Session titled “Inspiring Science | Fueling Progress | Revolutionizing Care.” Moderated by Drs. Flaherty and Curtis, the session addressed a range of topics, including translating cell atlases to medicines, artificial intelligence-based biomarkers, activity-based proteomics, and developing cancer therapies using bioorthogonal chemistry.

The plenary program also featured a Discovery Science session on Early Cancer Biology and Interception, as well as sessions on Profiling Tumor Ecosystems in Native Tissue Context; Evolution of the Genome, Microenvironment, and Host through Metastasis; and AI at the Interface of Accelerating Evidence Generation, Advancing Disparities Research, and Improving Trial Design.

Read a summary of the Opening Plenary Session on the AACR Blog

Early Cancer Biology and Interception: Read a summary of this Discovery Science Plenary Session on the AACR Blog

Profiling Tumor Ecosystems in Native Tissue Context: Read a summary of this Plenary Session on the AACR Blog

Evolution of the Genome, Microenvironment, and Host through Metastasis: Read a summary of this Plenary Session on the AACR Blog

AI at the Interface: Read a summary of this Plenary Session on the AACR Blog

AACR Annual Meeting 2024 Highlights: Vision for the Future—Read a summary of the Closing Plenary Session on the AACR Blog

The AACR Annual Meeting 2024 generated global interest, as the innovative cancer science presented in San Diego produced a significant amount of news coverage and social media activity.