Diane M. Simeone, MD, Laura and Isaac Perlmutter Professor of Surgery, Department of Surgery, professor, Department of Pathology, NYU Grossman School of Medicine, director, the Pancreatic Cancer Center, associate director, Translational Research, the Perlmutter Cancer Center, discusses the phase 1/2 EVEREST-1 trial (NCT05736731) evaluating the autologous CAR T-cell therapy A2B530 in patients with solid tumors.

The study is enrolling patients with solid tumors that express carcinoembryonic antigen (CEA) and have lost HLA-A*02 expression. To be eligible for enrollment, patients must have first undergone apheresis to store T cells for a future interventional study upon disease relapse during the BASECAMP-1 trial (NCT04981119). Through the apheresis and next-generation sequencing, the BASECAMP-1 trial is identifying patients who would be potential candidates to receive A2B530 in EVEREST-1, Simeone says.

BASECAMP-1 is enrolling a broad range of patients, and those that match the specific inclusion criteria of loss of HLA-A*02 expression and CEA overexpression will be eligible for EVEREST-1, Simeone notes. Although EVEREST-1 is currently limited to patients with a loss of HLA-A*02 expression, investigators plan to gradually broaden the HLA subtypes that will be eligible for the trial, Simeone adds, noting that the HLA-A*02 subtype accounts for approximately 30% of the United States population. The current inclusion criteria could create a funneling effect to include a smaller subset of patients; however, limiting enrollment to this subset of patients represents a good start for the study, Simeone expands.

As the approach broadens to include different activators or antigens expressed on the surface of tumor cells, this may increase the number of patients with solid tumors who will be eligible for enrollment, Simeone says. Investigators are also exploring approaches to best mitigate off-target effects of treatment with A2B530 so that the product can be delivered at a high payload while still allowing for the management of adverse effects associated with CAR T therapies, Simeone concludes.

Videos

Diane M. Simeone, MD, discusses the phase 1/2 EVEREST-1 trial evaluating the autologous CAR T-cell therapy A2B530 in patients with solid tumors.


Dr Simeone on the EVEREST-1 Trial Evaluating A2B530 in Solid Tumors

Diane M. Simeone, MD, Laura and Issac Perlmutter Professor of Surgery in the Department of Surgery; professor in the Department of Pathology; associate director of Translational Research at Perlmutter Cancer Center; professor in the Department of Pathology at NYU Grossman School of Medicine; and director of the Pancreatic Cancer Center of NYU Langone Health, discusses the importance of germline testing in pancreatic cancer.

All patients with pancreatic cancer should receive germline testing, says Simeone. Germline testing helps physicians to identify family members who might be at risk and help said family members undergo the screening they need. Patients should know whether they have family members or parents with pancreatic cancer, or whether they have a family history of pancreatic cancer—especially if it is associated with other cancer types. These patients should seek out a genetic counselor to determine whether or not they should get germline testing and screening done, says Simeone.

For those identified as high risk for pancreatic cancer, annual screening is recommended, along with a pancreatic MRI or magnetic resonance cholangiopancreatography, alternating with an endoscopic ultrasound. That should be done in the setting of a high-risk clinic, where there is a genetic counselor and a team of physicians involved in the patient’s care, concludes Simeone.

Diane M. Simeone, MD, discusses the importance of germline testing in pancreatic cancer.

Dr. Simeone on the Importance of Germline Testing in Pancreatic Cancer

Diane M. Simeone, MD, Laura and Issac Perlmutter Professor of Surgery in the Department of Surgery; professor in the Department of Pathology; associate director of Translational Research at Perlmutter Cancer Center; professor in the Department of Pathology at NYU Grossman School of Medicine; and director of the Pancreatic Cancer Center of NYU Langone Health, discusses the benefit of using a gemcitabine “sandwich approach” in patients with resectable pancreatic cancer.

 that are relevant to this space, says Simeone. For example, a phase 2 study that came from Europe enrolled patients with resectable or borderline resectable disease and randomized those patients to receive either surgery and adjuvant gemcitabine or neoadjuvant gemcitabine, surgery, and then gemcitabine afterward, almost like a sandwich approach, says Simeone.

The preliminary data suggest that patients who were treated with neoadjuvant gemcitabine and then surgery followed by more gemcitabine seemed to have improved overall survival, concludes Simeone.

Diane M. Simeone, MD, discusses the benefit of using a gemcitabine “sandwich approach” in patients with resectable pancreatic cancer.

Dr. Simeone on Benefit of Neoadjuvant Gemcitabine in Pancreatic Cancer

Diane M. Simeone, MD, Laura and Issac Perlmutter Professor of Surgery in the Department of Surgery; professor in the Department of Pathology; associate director of Translational Research at Perlmutter Cancer Center; and director of the Pancreatic Cancer Center of NYU Langone Health, explains which patients with pancreatic cancer should receive neoadjuvant therapy.

When considering which patients with locally-confined pancreatic cancer should receive neoadjuvant therapy, one must look at 3 categories: resectable, borderline, and locally advanced and unresectable categories, says Simeone.

For the resectable category, it is not in the guidelines that patients should receive neoadjuvant therapy, says Simeone. The standard of care is for patients to receive a high-quality, thin-slice CT scan for proper staging. If a tumor is determined to be resectable, then the patient can be offered a a surgical resection, explains Simeone. However, surgery alone is not the only tool used to treat those patients. The standard of care dictates that following recovery from surgery, which usually ranges from 4 to 6 weeks, patients should start adjuvant chemotherapy to help minimize the risk of disease recurrence, says Simeone.

Occasionally, up-front chemotherapy may be considered for some patients have resectable disease. For example, patients with larger tumors or tumors with a high level of CA 19-9 may be appropriate candidates for neoadjuvant chemotherapy, concludes Simeone.

Diane M. Simeone, MD, explains which patients with pancreatic cancer should receive neoadjuvant therapy.

Dr. Simeone on Selecting Patients With Pancreatic Cancer for Neoadjuvant Therapy

Diane M. Simeone, MD, director, Pancreatic Cancer Center, NYU Langone Health’s Perlmutter Cancer Center, discusses the impact of PARP inhibitors on pancreatic cancer.

PARP inhibitors alone contributed to doubling the progression-free survival in patients with pancreatic cancer, explains Simeone. In the post-POLO trial era, research is investigating the impact of PARP inhibitors plus another agent.

In the nonmetastatic setting, does a patient’s 

 status impact their adjuvant therapy? PARP inhibitors, according to Simeone, may eventually be used in a prevention setting for patients who have germline 

 mutations, though that is still several years away from consideration.

Diane M. Simeone, MD, discusses the impact of PARP inhibitors on pancreatic cancer.

Diane M. Simeone, MD

Articles

Dr Simeone on the EVEREST-1 Trial Evaluating A2B530 in Solid Tumors

Dr. Simeone on the Importance of Germline Testing in Pancreatic Cancer

Dr. Simeone on Benefit of Neoadjuvant Gemcitabine in Pancreatic Cancer

Dr. Simeone on Selecting Patients With Pancreatic Cancer for Neoadjuvant Therapy

Dr. Simeone on Impact of PARP Inhibitors on Pancreatic Cancer