Pancreatic Cancer: Novel Therapies, New Directions & Latest Treatments 2024

•Genetic testing and liquid biopsies for early detection are improving. Our ability to detect targets has progressed even from a couple of years ago. One of the greatest uses right now of liquid biopsies (from a blood draw) is being able to understand whether you have a KRAS mutation or not.

•Around 12% of people have a hereditary predisposition to pancreatic cancer, which can be identified through genetic testing.

•You should get “point of care” genetic testing (hereditary testing on your normal cells and testing on your tumor cells) at your first meeting, accompanied by educational videos to explain the test and its results.

•Although early detection of pancreatic cancer through tests may be expensive or infeasible today, using AI on medical records, and finding patients with certain kinds of diabetes, are identifying selected groups of patients who may benefit from screening tests. We are on the cusp of identifying pancreatic cancer with a lead time prior to clinical presentation, when, sadly, a lot of people are quite sick.

•Early research suggests immune response may predict outcomes in a pancreatic cancer vaccine trial. What are the challenges in improving tests and treatments for pancreatic cancer?

•It can be difficult to get high-quality tissue from the pancreas for testing.

•It is difficult to detect pancreatic cancer early from a liquid biopsy (blood draw) due to the lack of circulating tumor DNA in the blood.

•Pancreatic cancer has strong immune system suppression. What are the latest improvements in treatments for pancreatic cancer that are available today?

•KRAS inhibitors, including emerging combinations with chemotherapy and immunotherapy

•If you have homologous repair deficiency or have ineffective DNA repair (courtesy of a BRCA1, BRCA2 PALB2, and some other gene alterations), then there are chemotherapeutics, PARP inhibitors, and an emerging role for immunotherapy-based combinations. What are new treatments for pancreatic cancer that are being studied and may be available in the near future?

•About 15%, maybe 20%, of pancreatic cancer patients have deletion of a gene called “MTAP”, which is associated with other genes, which may have a treatment implication.

•Immunotherapy approaches for pancreatic cancer (e.g., personalized neoantigen vaccines, CD40 agonists which activate the immune system, CD73 inhibitors which target immune system suppression)

•Additional RAS-targeted drugs, such as RMC-6236, including in combinations How can you learn more and engage in choosing among the latest pancreatic cancer treatments?

•Get a second opinion from the big academic centers; usually, they will have a good sense of what's happening and where the field is headed and what trials are most relevant, and what might be an approximate horizon for access

•See our discussion with John Strickler, MD, on KRAS treatments .

•Check out PanCAN and other pancreatic cancer advocacy organizations

•Get a free second opinion from Cancer Commons

•Check out clinical trial resources and search tools at Massive Bio and myTomorrows, free services which review your medical records and make recommendations on suitable clinical trials for you, tailored to specifics, including what might be practical geographically

•Get germline and somatic testing at your diagnosis

•Research the importance of diabetes, weight changes, and other atypical symptoms as potential early warning signs The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action. You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health. Meeting Notes KEYWORDS pancreas cancer, people, disease, k ras, targeting, mutation, treatment, question, immunotherapy, part, pancreas, drugs, setting, chemotherapy, terms, therapeutics, important, tumor, early, field SPEAKERS Eileen O’Reilly (71%), Brad Power (9%), Rick Davis (5%), Gitte Pedersen (5%), Jill Rosen (3%), Roger Royse (3%), Francesca Paradiso (2%), Kathi Peterson (2%), Allen Morris (1%) CHAT CONTRIBUTORS Rick Davis, Robyn Caldwell, Allen Morris, Ellen Miller, Saed Sayad, David Plunkett, Roger Royse, Gitte Pedersen, Rob Weker SUMMARY Pancreatic cancer treatments can be tailored to individual patients based on their unique genetic profiles and immune systems. Emerging targets and therapies for pancreatic cancer include KRAS inhibitors, vaccines, and small molecule inhibitors. Genetic testing and liquid biopsies for early detection are improving, though there are challenges, such as the need for high-quality tissue and the difficulties in detecting targets due to the lack of circulating tumor DNA in the blood. Further research is needed to overcome technical challenges and improve early detection and treatment strategies. OUTLINE Pancreatic cancer research and treatment advancements, including targeted therapies and immunotherapies

•Dr. Eileen O'Reilly discusses pancreatic cancer research and future developments.

•There have been recent announcements of targeted therapies for KRAS-mutated tumors and homologous repair deficient subgroups.

•Genetic testing is evolving, including point-of-care testing and timely results.

•Researchers are exploring new treatments for pancreas cancer, including PARP inhibitors and high-dose therapy, with promising results in early trials. Emerging areas of targeted therapies and immunotherapies in pancreatic cancer

•KRAS mutations provide potential treatment targets, including combination with chemotherapy and immunotherapy.

•Immunotherapy approaches for pancreatic cancer include personalized neoantigen vaccines and CD40 agonists.

•Early research signals suggest immune response may predict outcome in pancreas cancer vaccine trial.

•Researchers explore personalized neoantigen vaccine approach for pancreas cancer, showing oncologic signal in early phase study. Challenges and potential solutions for early detection and monitoring of pancreatic cancer, including liquid biopsies and blood-based biomarkers.

•Challenges in obtaining high-quality tissue and DNA for liquid biopsies in pancreas cancer, including difficulty in detecting tumor shedding and obtaining usable biopsy samples.

•Early detection of pancreatic cancer through blood tests is challenging due to lack of circulating tumor DNA.

•Speaker discusses potential for blood-based biomarkers in early detection of pancreas cancer, particularly in high-risk groups such as those with a family history or diabetes diagnosis over age 50. Pancreatic cancer biomarkers and clinical trials for new treatments.

•Roger Royse luckily detected his pancreatic cancer early, despite subtle symptoms that were overlooked by his primary care physician.

•Dr. O'Reilly discusses RMC 6236, a pancreas cancer drug in phase 2 trials, with potential to move to phase 3 soon.

•She also mentions ongoing phase 1 and phase 1b combinations for pancreas cancer, with more opportunities for access to these drugs.

•She discusses the rarity of KRAS Q61 mutation in pancreatic cancer, with only 5% of cases having this mutation.

•Speaker 5 asks about clinical trials for KRAS Q61 mutation, expressing interest in potentially enrolling in a study despite being in stage four cancer and having already undergone chemotherapy for years.

•Dr. O'Reilly discusses the most common gene mutations in pancreatic cancer, including G12D, G12V, and G12R, and their response to current drugs.

•Advocacy organizations and clinical trial search platforms like Massive Bio and myTomorrows can help patients find relevant clinical trials tailored to their specific needs. Using AI and models to predict pancreatic cancer treatment response.

•Gitte Pedersen asks Dr. O’Reilly about the potential link between pancreatic microbiome and treatment resistance, as well as the availability of tests to guide chemotherapy delivery to the pancreas.

•Dr. O’Reilly discusses potential for microbiome analysis to predict cancer treatment response.

•Researchers are using AI and EMR data to identify pancreatic cancer patients 12 months prior to d diagnosis. Early detection and treatment of pancreatic cancer, with a focus on AI tools and community clinics.

•Dr. O'Reilly highlights the potential of AI tools in early detection of pancreatic cancer, citing examples of successful implementation in health systems.

•Rick Davis questions the choice of treatment for patients in community settings, where healthcare providers may not be aware of the importance of ATR2 expression.

•Dr. O’Reilly discusses adenocarcinoma of the pancreas, including prognosis and treatment options.

•Comprehensive cancer centers are best for optimal care. Cancer treatment options for a patient with a KRAS mutation.

•Dr. O’Reilly discusses concerns about using an older drug combination for a patient with KRAS mutation.

•She mentions that high expression of the signal is more modest than expected in pancreatic cancer, suggesting that other factors may be at play.

•In phase 1 trials, the extent of prior treatments is less restrictive compared to phase three trials, which typically require only one line of prior chemotherapy. Immunotherapy for pancreatic cancer, including genetic profiling and liquid biopsy.

•Understanding the genetic profile of tumor and immunotherapy approaches are key considerations for patients with pancreatic cancer.

•Key takeaway: Loss of second gene copy predicts benefit from BRCA-targeted therapy.

•Francesca Paradiso discusses using PBMCs for immunoprofiling to predict outcomes in immunotherapy.

•Dr. O'Reilly believes there is a subset of pancreas cancer patients who may benefit from immunotherapies, and the immune environment is important for these agents.