Speakers at the 2022 Virtual Growth Conference’s session on pancreatic cancer acknowledged the exceptional challenges while extolling advances in immune-based therapies and combination approaches.
The tide is starting to turn in pancreatic cancer, finally bringing the kind of advances that have been seen in other types of cancers to this difficult-to-treat condition. Speakers at the 2022 Virtual Growth Conference’s session on pancreatic cancer, sponsored by the Maxim Group and M-Vest, acknowledged the exceptional challenges while extolling advances in immune-based therapies, combination approaches, novel molecules and new delivery vehicles for checkpoint inhibitors.
“Getting the drug into the tumor is one of the biggest challenges,” Shaun Bagai, CEO of RenovoRx, Inc., said. His company currently is enrolling the TIGeR-PaC Phase III clinical trial, which delivers intra-arterial gemcitabine directly to the tumor using a dual-balloon infusion catheter called RenovoCath. With the Phase III study, “We’re hoping to confirm early results (from other studies) that indicated a 28-month mean survival. We expected 12-to-15-month survival, so this is a huge bonus for patients.”
Data from the RR2 Observational Registry study, released last autumn, showed a median overall survival of 23 months for patients who had undergone prior radiation therapy, versus nearly 17 months for those who had received prior chemotherapy, and nearly 6 months for treatment naïve patients.
AIM ImmunoTech is developing Ampligen (rintatolimod).
“It has potential in a broad spectrum of antitumor and antiviral applications, including for chronic fatigue syndrome (approved in Argentina), and for long COVID,” Tom Equels, CEO, said. “We repurposed Ampligen® for oncology. It is in Phase II trials for late-stage patients with pancreatic cancer, and also for ovarian cancer.” It is being assessed as a single agent and in combination with checkpoint inhibitors.
Panabela Therapeutics is developing a polyamine (PA) analogue of spermine, SBP-101 (diethyl dihydroxyhomospermine), as a polyamine metabolic inhibitor. A Phase I trial showed this therapeutic inhibited growth in six human pancreatic ductal adenocarcinoma (PDA) cell lines and three murine xenograft tumor models. “All results were better than (standard-of-care) gemcitabine alone, so it will move into a double-blind Phase II/III trial this year,” Jennifer Simpson, CEO, said.
Key opinion leaders working with Panabela have suggested, Simpson said, that SBP-101 could be used to reduce the tumor burden before surgery. “This is important because, although 80% of patients are diagnosed at stage 4, 20% are still diagnosed at a stage when the tumor is resectable. That’s worthy of our focus, as well.”
Synthetic Biologics, which recently acquired the oncolytic virus developer VCN Biosciences, just reported favorable outcomes from a Phase I study involving VCN-01. This intravenous oncolytic adenovirus was used with or without standard-of-care chemotherapy in advanced solid tumors. Data showed viral exposure in the primary tumor and liver metastases, replication within the tumor and the potential to remodel the tumor matrix to promote tumor inflammation, according to the company.
“The oncolytic virus inflames the tumor…to induce apoptosis. We are planning to launch a randomized Phase II trial, and are one of the few companies with effective targeting after systemic administration in tumors,” Manel Cascalló, Ph.D., director general-European region, and former chairman and CEO of VCN Biosciences, said.
These advances are so notable because pancreatic cancer is particularly challenging. These tumors are avascular, which makes it difficult to deliver therapeutics inside the tumor. “That’s one of the reasons checkpoint inhibitors don’t work well for pancreatic cancer,” Cascalló said. “The T cells cannot penetrate the tumors.”
That challenge leaves room for companies to develop therapeutics that can infiltrate the tumor effectively. Combination therapeutics, therefore, are a promising approach that may use one compound to infiltrate the mass and another to attack the tumor. “There is a lot more to learn about…the immune system and what is priming the environment,” Simpson said. Her observation alludes to the challenge of adding therapeutics to standard-of-care chemotherapy.
The strategies of these and other companies have the potential for synergistic combinations as well as notable advances in single agents, the panelists agreed.
For example, the Erasmus Center in the Netherlands completed a small, 27-patient study that found “Ampligen™ extended survival beyond that of the standard of care by eight months in late-stage patients,” Equels said. “It stimulates the innate immune system pathways, which have natural anti-tumor effects. In vitro studies also showed the therapeutic affects the microenvironment of the tumor by altering the ratio of T regulator and T effector cells, thus changing the tumor from cold (camouflaged from the immune system) to hot (where it can be seen).” A 90-subject Phase II trial is planned.
“This malignancy is a death sentence for most people,” Equels said. “There are very few symptoms until it’s almost too late – the tumors are immunosilent.” So, when people are diagnosed, they usually are in the late stages of the condition.
The choice of endpoints for studies is evolving, the panelists agreed, and regulatory agencies are somewhat flexible in this space because there are so few approved treatment options. Equels said, for example, that the percentage of cells that are expressing TLR3 could be a predictor of efficacy for Ampligen, which is a toll-like receptor 3 agonist. Nonetheless, survival is the primary endpoint and is likely to remain so indefinitely. In pancreatic cancer, “If people are surviving, it’s not the result of the placebo effect. You’re doing something right.”
