Pancreatic cancer: Are we close to finding an effective treatment?

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A type of cancer that begins in the pancreas – an organ located behind the stomach that plays a key role in digestion and blood sugar regulation – pancreatic cancer is considered one of the most aggressive and deadliest cancers around, largely because it is often diagnosed at an advanced stage. It has been increasing in incidence for decades and is now the third leading cause of cancer death in the U.S., with projections indicating that it will be second only to lung cancer in its lethality by 2025.

Pancreatic ductal adenocarcinoma (PDA), the most common type of pancreatic cancer, accounts for at least 90% of cases and is considered fatal in most instances, with a five-year survival rate of only 12%. Although this statistic has driven significant research efforts into this type of cancer in recent decades, little progress has been made in the understanding and treatment of pancreatic cancer and the investment has yet to result in a meaningful increase in the five-year survival rate.

To really put the numbers into perspective, the American Cancer Society estimates that, in 2024, approximately 67,440 people in the U.S. will be diagnosed with pancreatic cancer and about 51,980 of those people are expected to succumb to the disease.

But why exactly is pancreatic cancer so difficult to treat and what drugs are currently in the therapeutic pipeline?

Why is pancreatic cancer so difficult to treat?

There are several challenges involved here. The location of the pancreas, which is surrounded by several vital structures, makes pancreatic cancer not just difficult to diagnose, but also to treat surgically. Plus, pancreatic cancer is quite resistant to most available systemic anti-cancer agents.

In terms of diagnosis, because the pancreas is located so deep inside the body, tumors often go undetected until the cancer has spread to other parts of the body. When diagnosis happens at this stage, the cancer is very difficult to treat. Additionally, in the early stages of pancreatic cancer, there may be no symptoms at all, or they may be vague. Generally, if there are symptoms present, they include things like indigestion, weight loss, and fatigue, which are also symptoms of many other more common health conditions, meaning it is hard to actually make a diagnosis of pancreatic cancer.

If the cancer is detected before it has metastasized, its deep location once again poses a problem; accessing it for a surgical procedure is extremely complicated. Furthermore, pancreatic tumors are invasive in the abdomen and often cannot be completely removed during surgery, and, in some cases, they become so entangled in blood vessels that feed other vital organs that surgery is not a viable option.

Other treatment options are also not particularly viable for pancreatic cancer. This is because the cancer cells create a cocoon of collagen fibers around the tumor, shielding it not just from the body’s immune system, but also from standard-of-care treatments like chemotherapy. Furthermore, immunotherapy is not a great option either. While some tumors contain dormant immune cells called lymphocytes that may be awakened by checkpoint inhibitors, pancreatic cancer cells are low in immunogenicity and are, therefore, less likely to generate an immune response.

Promising pancreatic cancer clinical trials

However, despite these difficulties, there is still reason to be optimistic about the current clinical landscape for pancreatic cancer, as several biotech companies are making promising strides in developing new and more effective treatments.

Oncolytics Biotech advancing pelareorep for pancreatic cancer

Canadian company Oncolytics Biotech is developing a drug called pelareorep, which has shown promise in a number of cancer types, particularly breast and pancreatic cancer.

Pelareorep is a nonpathogenic, oncolytic virus that can be delivered intravenously and works by generating, recruiting, and training immune cells to recognize and kill cancer while remodeling the tumor microenvironment to give access to immune cells, inducing a cascade of inflammatory responses that enable the immune system to destroy the tumor while sparing normal tissue. These responses, which include PD-L1 upregulation and enhanced T-cell infiltration, are partially due to pelareorep’s ability to introduce double-stranded RNA into cancer cells.

Although the therapy has demonstrated single-agent activity, according to Oncolytics, it can also work in synergy with chemotherapy, immune checkpoint inhibitors (ICIs), CAR-T cell therapy, proteasome inhibitors, bispecific antibodies, and CDK4/6 and PARP inhibitors to enhance its antitumor potential and meaningfully extend patient remissions. This combination approach is what Oncolytics are pushing forward with for the treatment of pancreatic cancer.

In 2022, pelareorep was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) in combination with Roche’s anti-PD-L1 checkpoint inhibitor atezolizumab, and the chemotherapeutic agents gemcitabine and nab-paclitaxel, for the treatment of advanced/metastatic pancreatic ductal adenocarcinoma.

Oncolytics is currently conducting the GOBLET trial, a phase 1/2 study, to examine the potential of certain combination therapies with pelareorep for gastrointestinal cancers, including advanced/metastatic pancreatic cancer. According to the company, the aforementioned combination with atezolizumab and standard-of-care chemotherapy has already shown a promising efficacy signal.

To expand the potential benefit of pelareorep, Oncolytics decided to add another cohort to the GOBLET study to evaluate pelareorep combined with modified FOLFIRINOX both with and without atezolizumab, which is being funded by a $5 million grant from the Pancreatic Cancer Action Network (PanCAN). Earlier this month, Oncolytics reported that safety data from patients treated with pelareorep and a modified FOLFIRINOX regimen support expanding its use across additional chemotherapy options.

In 2024, Oncolytics also announced a preliminary collaboration with the Global Coalition for Adaptive Research (GCAR) to evaluate pelareorep in treating first-line metastatic pancreatic ductal adenocarcinoma, with the intention of expediting the development of the drug by reducing trial costs and time, potentially delivering effective treatment to patients sooner.

Candel Therapeutics receives orphan drug designation for pancreatic cancer candidate CAN-2409

Candel Therapeutics is also focusing on viral immunotherapy for the treatment of various cancers, including pancreatic cancer.

Its candidate, called CAN-2409, uses a genetically modified adenovirus – the same virus that is used for gene therapy – and works by delivering the herpes simplex virus thymidine kinase gene into tumor cells, which then express HSV-thymidine kinase. Alongside this, approved anti-herpes drug valacyclovir is also administered to the patient, ultimately activating a very strong inflammatory signal to the tumor microenvironment. Meanwhile, the adenoviral serotype 5 capsid protein also elicits a strong pro-inflammatory signal in the tumor microenvironment, creating the optimal conditions to induce a specific CD8+ T cell-mediated response against the injected tumor and uninjected distant metastases for broad and systemic anti-tumor activity.

Candle’s candidate received orphan drug designation from the FDA in April 2024 for the treatment of pancreatic cancer. This came thanks to positive phase 2 interim data announced by the company earlier that month, which showed notable improvements in estimated median overall survival of 28.8 months after experimental treatment with CAN-2409 versus only 12.5 months in the control group in borderline resectable pancreatic ductal adenocarcinoma. Additionally, at 24 months, the survival rate was 71.4% in patients treated with CAN-2409 versus only 16.7% in the control group after chemoradiation.

CAN-2409 was also granted fast track designation in pancreatic cancer by the FDA in December 2023.

CytomX Therapeutics’ partnership with Amgen to develop CX-904, a T cell engager for pancreatic cancer

In 2017, CytomX Therapeutics partnered with Amgen to co-develop a T-cell engaging bispecific against the epidermal growth factor receptor (EGFR), a highly validated oncology target expressed on multiple human cancer types, with 90% of pancreatic cancers showing high expression of EGFR.

The candidate in question here is called CX-904. Being a bispecific antibody, it targets both EGFR on cancer cells and the CD3 receptor on T cells. The drug is currently in a phase 1a dose-escalation study in patients with advanced solid tumors.

In May 2024, CytomX announced that CX-904 not only demonstrated a favorable safety profile in the ongoing trial, with no cytokine release syndrome, but also presented encouraging initial signs of efficacy in advanced pancreatic cancer, including two of six patients (33%) with a confirmed partial response, and all six patients (100%) with disease control.

With such promise specifically for the treatment of pancreatic cancer, CX-904 could well be set to move forward in this indication once the phase 1a trial is completed.

Hope rising in the fight against pancreatic cancer

Because of the aforementioned trials, as well as an improvement in diagnostics, with a recent study recently claiming that a blood test can accurately detect early-stage pancreatic cancer with 97% accuracy, hope is rising that there could soon be better outcomes for pancreatic cancer patients.

Additionally, the global pancreatic cancer treatment market size, which was estimated at $2.92 billion in 2024, is expected to grow at a compound annual growth rate (CAGR) of 12.30% from 2025 to 2030. According to Grand View Research, the growing aging population and the associated rise in lifestyle-related diseases are contributing to an increasing demand for specialized treatments, and strong governmental support through healthcare funding and initiatives aimed at early diagnosis and access to advanced therapies will be the driving factors that further propel the market.

Certainly, if we take into account the overall promise and positive results that the current product pipeline has produced, it might not be long before we see regulatory approval for a pancreatic cancer treatment that can finally make a difference for patients.