ASCO Recap

The annual American Society of Clinical Oncology (ASCO) meeting brings together scientists from across the country who are studying every type of cancer to share the latest results from the lab and the clinic. This year’s headlines focused heavily on a small study of immunotherapy in rectal cancer that achieved 100% remission in all 14 participants. There were exciting developments in pancreatic cancer, as well. Reports on two pancreatic cancer clinical studies offer promising insights into the possibilities of delivering the right therapies to the right patient.  

We talked with Andrew Rakeman, PhD, Lustgarten’s VP of Research to learn more about the studies generating the most excitement among pancreatic cancer researchers. 

Phase I trial of adjuvant, individualized mRNA neoantigen vaccine

LEAD RESEARCHERS: Vinod Balachandran, MD, and Benjamin Greenbaum, PhD 

If mRNA vaccines sound familiar, you can likely thank the COVID-19 vaccines which helped protect millions of people around the world from developing the most severe symptoms of the respiratory disease. However, long before the pandemic, scientists were already studying the use of messenger RNA—so called because its sole purpose is to carry instructions to cells—in vaccines to induce specific immune responses against everything from cancer cells to viruses. 

At ASCO, Dr. Vinod Balachandran of the David M. Rubenstein Center for Pancreatic Cancer Research, presented results of the first trial testing a personalized mRNA vaccine for pancreatic cancer. The ASCO presentation came on the heels of the team’s second paper published in the scientific journal Nature. 

The two-year trial, funded by the Pancreatic Cancer Collective (PCC)—a partnership between the Lustgarten Foundation and Stand Up To Cancer—was the culmination of years of research leading to the critical discovery that long-term pancreatic cancer survivors have specific immune responses that the team hoped to mimic with the vaccines. This discovery was the topic of the first paper Dr. Balachandran and his team at Memorial Sloan Kettering Cancer Center published in a 2017 edition of Nature. 

To test their hypothesis in a clinical setting, researchers enrolled pancreatic cancer patients eligible for surgery. After surgical removal of the tumors, scientists analyzed tissue samples using Artificial Intelligence (AI) and machine learning to design patient-specific vaccines. The designer mRNA vaccines included up to 20 neoantigens—proteins that form only on cancer cells—specific to individual patients. Patients were then immunized with their personalized mRNA vaccine and treated with chemotherapy. Patients were tracked for immune response to the vaccine and for disease recurrence. 

Results:

Half of the 16 patients treated in this study showed an immune response to the vaccine. In those eight patients none have shown recurrence for up to 30 months (median follow up 18 months) and they are continuing to be followed. In contrast, the patients that didn’t respond to the vaccine had a median recurrence-free survival of just over a year.   

Why it’s exciting:

The results suggests the possibility of durable protection against pancreatic cancer, if an immune response can be driven against tumor-specific targets. The study also demonstrates the feasibility of developing patient-specific, personalized vaccines in a clinically relevant timeframe. More research is needed to better understand why half of the patients did not respond to the vaccine. 

More Info: Study Abstract on ASCOpubs.org

PRINCE Trial: Distinct biosignatures associated with survival after chemoimmunotherapy in a randomized, three-arm phase II study in patients with metastatic pancreatic cancer

LEAD RESEARCHER:  Lacey J. Padrón, PhD 

Could a combination of immunotherapy and chemo cure advanced metastatic pancreatic ductal adenocarcinoma (PDAC)? That’s the question scientists are exploring through the PRINCE trial that also is generating excitement among researchers. 

Results:

An initial clinical research study suggested a combination of chemotherapy (gemcitabine and nab-paclitaxel), immune checkpoint inhibitor (Nivolumab) and a CD40 agonist (APX005M)—a cell surface molecule—could shrink tumors in PDAC. Based on early results, scientists expanded the trial to a larger, Phase II study which failed to produce a significant number of positive patient outcomes. Despite the setback, researchers discovered a silver lining—using state-of-the-art clinical data analysis tools, scientists identified distinct biosignatures associated with longer survival in the treated patients—biosignatures that could be helpful in predicting which future patients may benefit from this treatment.  

Why it’s exciting: 

Though more work is needed to test the approach in prospective clinical trials, scientists are optimistic the signatures may be an effective tool to identify the right patients to treat with this combination. By understanding the immune features associated with response to the combined treatment, physicians may be better equipped to select patients for a particular treatment, as well as devising strategies to boost response in patients who lack the specific biosignatures.  

More Info: Study Abstract on ASCOpubs.org