World Pancreatic Cancer Day 2024: Looking Back at Progress in Cell and Gene Therapy

According to the Hirshberg Foundation for Pancreatic Cancer Research, approximately 66,440 Americans will be diagnosed with pancreatic cancer in 2024 and more than 51,750 Americans will die from pancreatic cancer. Notably, pancreatic cancer has the highest mortality rate of all major cancers and is one of the leading causes of cancer deaths in the United States, sitting only behind lung cancer and colon cancer.

An important new frontier for the treatment of pancreatic cancer is cell therapy and gene therapy and a number of companies and academic institutions are now pursuing the development of a range of such advanced therapeutics for the disease. In honor of World Pancreatic Cancer Day, held on the third Thursday of November each year, CGTLive® is taking a look back at some of the progress that has been made for cell therapy and gene therapy candidates in pancreatic cancer over the past year. Click the "READ MORE" buttons for more details and information about each item.

FDA Removes Clinical Holds Previously Placed on 3 of CARsgen's Oncology Cell Therapies

November 7, 2024 — The FDA has removed clinical holds from the phase 1b/2 LUMMICAR 2 clinical trial (NCT03915184) evaluating CARsgen's BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapy zevorcabtagene autoleucel (zevor-cel) for relapsed/refractory (r/r) multiple myeloma (MM), the phase 1b/2 ELIMYN18.2 (ST-02) clinical trial (NCT04404595) evaluating its Claudin18.2-directed CAR-T satricabtagene autoleucel (satri-cel) for gastric/pancreatic cancers, and a phase 1/2 clinical trial (NCT06333509) evaluating its GPRC5D-directed CAR-T CT071 for r/r MM and r/r primary plasma cell leukemia.

The clinical holds on the 3 products were originally placed by the FDA in December 2023 based on chemistry, manufacturing, and controls (CMC)-related questions that arose from findings of an inspection of CARsgen’s manufacturing facility in Durham, North Carolina, according to a notice the company provided to the Hong Kong Stock Exchange on December 12, 2023. At the time, the company stated that it planned to conduct a comprehensive review and improve its current Good Manufacturing Practices (cGMP) at the facility, noting that it is “committed to working closely with the FDA to address the findings to ensure the smooth progress and production quality for clinical trials and launching applications.”

CGTLive® has previously provided coverage of the ELIMYN18.2 clinical trial, which is evaluating satri-cel in heavily pretreated Claudin18.2 (CLDN18.2)-positive advanced gastric/gastroesophageal (GC/GEJ) or pancreatic cancer (PC). The ELIMYN18.2 trial is evaluating the safety and efficacy of satri-cel in patients with advanced GC/GEJ or PC whose disease had progressed or was unresponsive to at least 2 prior lines (GC/GEJ) or 1 prior line (PC) of systemic therapy.

A2 Bio’s Trial for Solid Tumor Tmod CAR-T A2B694 Doses First Patient

May 19, 2024 — The first patient has been dosed in A2 Biotherapeutics (A2 Bio)’s phase 1/2 EVEREST-2 clinical trial (NCT06051695) evaluating A2B694, an investigational logic-gated Tmod CAR-T therapy, in patients with mesothelin (MSLN)-expressing solid tumors that have lost HLA-A*02 expression.

EVEREST-2 is recruiting patients with solid tumors with MSLN-expression, including lung cancer, colorectal cancer, pancreatic cancer, ovarian cancer, and mesothelioma cancers. Patients must have previously participated in the company’s BASECAMP-1 screening study (NCT04981119) that is identifying patients with solid tumors that are positive for somatic human leukocyte antigen (HLA)-A*02 loss of heterozygosity (LOH). The Tmod approach is intended to allow the CAR-T to selectively kill tumor cells while sparing healthy tissue by conferring the CAR T-cells with an “activator” that targets MSLN and a “blocker” that protects cells that do not have HLA-A*02 LOH.

“Dosing our first patient in this trial is a key step to provide a precise, novel CAR-T therapy to patients with solid tumors that express mesothelin with no curative treatment options,” William Go, MD, PhD, the chief medical officer of A2 Bio, said in a statement. “Sadly, current treatment options for these patients are palliative and limited by toxicity in the recurrent, unresectable, locally advanced or metastatic setting. All of us at A2 Bio would like to thank participating patients, investigators, and clinical care providers.”

Next ACGT Grant to Focus on Cell and Gene Therapy for Pancreatic Cancer

May 17, 2024 — During the ACGT Summit 2024 in March, Alliance for Cancer Gene Therapy announced the next research grant – the ACGT Edward Netter Memorial Investigator Award in Cell and Gene Therapy Research for Pancreatic Cancer.

Pancreatic cancer takes the lives of nearly 52,000 people in the United States each year. In 2011, ACGT Co-Founder Edward Netter died of this cancer, which is predicted to become the second leading cause of cancer-related death worldwide by 2030.

The ACGT Edward Netter Memorial Investigator Award in Cell and Gene Therapy Research for Pancreatic Cancer will be a $500,000 grant. It is designed to stimulate research and clinical progress in advancing cancer cell and gene therapy research to bring new hope to pancreatic cancer patients.

Tumor Agnostic Deltarex-G+ Gene Therapy Demonstrates Activity in Breast, Pancreatic, Sarcoma Cancers

May 11, 2024 — CCNG1-targeted Deltarex-G gene therapy plus an FDA approved drug (Deltarex-G+) showed some evidence of response in patients’ tumors, including pancreatic cancer, breast cancer, and sarcoma. All tested tumors had enhanced CCNG1 expression.

Data from the BLESSED expanded access study (NCT04091295) were presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland, by Erlinda Gordon, MD, founder and president, Aveni Foundation, and director, biological and immunological therapies, and chairman, institutional biosafety committee director, Cancer Center of Southern California/Sarcoma Oncology Center, and founder, chief operating officer, and FDA liaison, Counterpoint Biomedica.

“Deltarex-G is the only tumor targeted gene therapy that can be injected intravenously and it in vivo gets into the tumor microenvironment by binding to abnormal signature proteins in the tumor. So, it's unlike the ex vivo gene therapies for cancer... it's an off the shelf gene therapy product that has a navigation system that goes to the tumor itself,” Gordon told CGTLive during the meeting. “We tested that... CCNG1 is present in all the tumor types that we have tested including sarcoma, pancreatic cancer, breast cancer, testicular cancer, bladder cancer, so that we think it's a tumor agnostic therapy, rather than looking for a very rare oncogene to target."

CAR TEAM Cells Show Promise in Multiple Preclinical Models of Pancreatic Cancer

April 10, 2024 — In multiple preclinical models, chimeric antigen receptor (CAR) T-cell–engaging molecule (TEAM) cells modified tumor stroma and exhibited increased pancreatic ductal adenocarcinoma (PDAC) antitumor activity.

Data on the CAR-TEAM cells in models of pancreatic cancer were published in an online paper for the American Association for Cancer Research (AACR) Annual Meeting 2024, held on April 5-10, 2024, in San Diego, California.

“In pancreatic cancer, about 100% of the adenocarcinoma cells will express MSLN but there is a significant stroma made by cancer-associated fibroblasts (CAFs) that turns out to be quite dense and can be inhibitory toward the T-cells entering,” senior author Marcela V. Maus, MD, PhD, Associate Professor of Medicine, Harvard Medical School, and director, cellular immunotherapy, Cancer Center, Massachusetts General Hospital, said during a talk about CAR TEAMS at the AACR meeting.

REFEENCE
1. Pancreatic Cancer Facts. Hirshberg Foundation for Pancreatic Cancer Research. Website. Accessed November 21, 2024. https://pancreatic.org/pancreatic-cancer/pancreatic-cancer-facts/