MD Anderson Research Highlights Special Edition: ESMO 2024

The University of Texas MD Anderson Cancer Center’s Research Highlights provides a glimpse into recent basic, translational and clinical cancer research from MD Anderson experts. This special edition features upcoming oral presentations by MD Anderson researchers at the 2024 European Society for Medical Oncology (ESMO) Congress focused on clinical advances across a variety of cancer types.

Featuring promising novel immunotherapies and targeted therapies, predictive biomarkers, and insights into COVID mRNA vaccines and immunotherapy responses.

In addition to the studies summarized below, forthcoming press releases will feature the following oral presentations:

• Initial results from a first-in-human study of the B7-H4-directed antibody-drug conjugate AZD8205 (puxitatug samrotecan) in patients with advanced/metastatic solid tumors (Abstract 606O)
• NKT2152, a novel oral HIF-2α inhibitor, in participants with previously treated advanced clear cell renal carcinoma: Preliminary results of a Phase I/II study (Abstract 1690O)
• Haloperidol and lorazepam for agitated delirium in patients with advanced cancer: A multicenter, double-blind, randomized clinical trial (Abstract 1476O)

Pembrolizumab provides lasting cancer control in patients with localized MSI-H/dMMR cancers (Abstract 510MO)

Cancers with defects in DNA mismatch repair have high microsatellite instability (MSI-H/dMMR) and are more responsive to immune checkpoint inhibitors. In a study led by Kaysia Ludford and Michael Overman, researchers assessed the long-term effects of pembrolizumab in 35 patients with MSI-H/dMMR.

After a median follow-up of nearly three years, the disease-free survival rate was 80% and the overall survival rate was 94%. Additionally, almost 40% of patients achieved complete responses, with their cancers becoming undetectable.

In the non-operative group, most patients preserved their affected organs. Importantly, the study found clearance of circulating tumor DNA (ctDNA) during treatment was linked with better patient outcomes, suggesting that ctDNA could be a useful tool for monitoring treatment efficacy. These results highlight pembrolizumab’s potential for long-term cancer control and organ preservation in this patient population. Ludford presented the findings Sept. 14.

Next-generation combination treatment demonstrates safety and early efficacy in CDK4/6-treated HR+ HER2- breast cancer (Abstract 618MO)

CDK4/6 inhibitors combined with endocrine therapy have improved survival outcomes for patients with HR+ HER2- metastatic breast cancer, but on-target toxicities and acquired resistance are common. A Phase Ib/II trial led by Timothy Yap, evaluated a novel combination of the next-generation CDK4-selective inhibitor, atirmociclib (formerly PF-07220060), and the first-in-class selective CDK2 inhibitor, PF-07104091, to investigate safety and whether the combination can overcome acquired resistance.

Atirmociclib does not target CDK6, which has been associated with many of the known toxicities reported with the approved CDK4/6 inhibitors. In 26 heavily pretreated patients with metastatic breast cancer, the objective response rate was 27.8%, the disease control rate was 55.6% and the median progression-free survival was 8.3 months.

The combination was well-tolerated and had a manageable safety profile overall, with neutropenia being the most common grade three or higher adverse event. Dose expansion arms of the trial are ongoing. Yap presented the findings Sept. 14.

Baseline cytokine levels may predict dyspnea treatment response (Abstract 1821MO)

Dyspnea, or breathlessness, is a common symptom among many patients with advanced cancer. Previous results from a trial led by David Hui, demonstrated that both high-dose dexamethasone and placebo improved dyspnea, but there was no significant difference between the two arms.

In a secondary analysis of trial results, researchers evaluated blood samples from 45 trial patients to explore predictive biomarkers. Those treated with dexamethasone had significantly decreased levels of cytokines TNF, IL-6 and IL-8 over 14 days, unlike those treated with placebo.

Higher baseline cytokine levels were associated with a greater reduction in dyspnea intensity in the dexamethasone group and a smaller reduction in the placebo group, highlighting their potential as predictive biomarkers. These findings may have implications for personalizing dexamethasone treatment and understanding the placebo response. Dr. Hui presented the final data Sept. 15.

New combination therapy shows efficacy in advanced melanoma (Abstract 71MO)

While checkpoint inhibitors provide significant clinical benefit for patients with metastatic melanoma, many still develop treatment resistance. In a Phase I/II trial, researchers led by Salah-Eddine Bentebibel and Adi Diab, investigated an intratumoral injection of CD40 agonist sotigalimab combined with immunotherapy drug pembrolizumab in 32 untreated patients with melanoma.

The combination achieved an objective response rate of 50% with a 91% disease control rate. The study demonstrated that sotigalimab effectively engaged the CD40 pathway, boosting the infiltration and activation of antigen-presenting cells. The combination led to a strong activation of both innate and adaptive immune responses at the injection site as well as throughout the body.

Additional analyses showed a higher clonality of T cells associated with improved clinical outcomes. The combination was well-tolerated and safe, highlighting its potential as a treatment alternative for patients with metastatic melanoma. Diab will present the findings Sept. 16.

COVID mRNA vaccines associated with improved responses to immunotherapy in multiple cancers (Abstract 995MO)

Personalized mRNA vaccines have improved the effectiveness of immune checkpoint inhibitors in preclinical models. To investigate the possible effects of COVID mRNA vaccines, researchers led by Adam Grippin and Steven Lin, analyzed data from more than 8,000 patients with various cancers.

Patients who received a COVID mRNA vaccine within 100 days prior to their biopsies had a significant increase in the immune checkpoint protein PD-L1, which is targeted by several checkpoint inhibitors. Among patients with non-small cell lung cancer (NSCLC) who were treated with checkpoint inhibitors, those who received a COVID mRNA vaccine lived twice as long as those who did not.

Patients with metastatic melanoma who received the vaccine also had better outcomes, including improved survival and a lower risk of disease progression. This study suggests that COVID mRNA vaccines may enhance cancer immunotherapy by increasing PD-L1 expression, leading to improved survival. Grippin will present the findings Sept. 16.

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