Recognized as one of the most lethal cancers, researchers are striving to improve survival rates for pancreatic cancer patients by focusing on earlier detection. According to Johns Hopkins Medicine, up to 80% of patients are diagnosed at advanced stages, which are significantly harder to treat. A new study published in the journal Cell Genomics demonstrates that researchers have identified key protein biomarkers for early detection of pancreatic cancer. Analysts at Towards Healthcare project the pancreatic cancer market to grow at a rate of 13.7% CAGR, hitting US$7.4 billion by 2032. Meanwhile, biotech developers are fervently working on groundbreaking medical treatments to greatly improve patient health outcomes.
During this year’s American Society of Clinical Oncology (ASCO) Annual Meeting, Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) highlighted two abstracts related to their novel immunotherapy, pelareorep. Among these was a trial-in-progress abstract for cohort 5 of the GOBLET study. This cohort will explore the effectiveness of combining pelareorep with modified FOLFIRINOX (mFOLFIRINOX), with and without atezolizumab, in newly diagnosed patients with metastatic pancreatic ductal adenocarcinoma (PDAC).
“The first abstract outlines the design of a new GOBLET PDAC cohort that could significantly expand the potential of the company’s pancreatic cancer program,” said Dr. Matt Coffey, President and CEO of Oncolytics. “The chemotherapy regimens of mFOLFIRINOX and gemcitabine/nab-paclitaxel are the two most common standards of care in metastatic pancreatic cancer. We previously reported that the combination of pelareorep, gemcitabine, nab-paclitaxel, and atezolizumab yielded tumor response rates nearly triple historical results. Should the combination of pelareorep and mFOLFIRINOX produce a similarly positive outcome, an even broader range of metastatic PDAC patients may benefit from pelareorep-based therapy.”
The cohort is supported by a US$5 million Therapeutic Accelerator Award grant from the Pancreatic Cancer Action Network (PanCAN). Oncolytics Biotech expects enrollment for this cohort to start this quarter.
The GOBLET cohort 5 abstract and poster detail important elements of a study using a Simon two-stage design to assess patients with newly diagnosed metastatic PDAC. In the first stage, 15 evaluable patients per arm are randomly assigned to one of two treatments: pelareorep with mFOLFIRINOX, or pelareorep with mFOLFIRINOX and atezolizumab. The co-primary endpoints of the study are objective response rate and safety. Secondary and exploratory endpoints include further efficacy evaluations, such as progression-free and overall survival, along with biomarker assessments. If the first stage achieves its success criteria, one or both treatment arms may proceed to Stage 2, enrolling an additional 17 evaluable patients per arm. Throughout the study, blood and tumor samples will be collected for translational analyses.
Another important ASCO presentation came from Verastem, Inc. (NASDAQ: VSTM), which presented positive initial interim safety and efficacy results from an ongoing Phase 1/2 trial evaluating its avutometinib plus defactinib in combination with gemcitabine and Nab-paclitaxel in the first-line in patients with metastatic pancreatic cancer. Like with Oncolytics’ pelareorep, Verastem received funding from PanCAN through its Therapeutic Accelerator Award for avutometinib.
“Verastem was the inaugural recipient of the PanCAN Therapeutic Accelerator Award, which has been an important part of PanCAN’s approach to advancing innovative treatments for pancreatic cancer,” said Anna Berkenblit, M.D., MMSc, Chief Scientific and Medical Officer at PanCAN. “There is a critical need for new treatment options in this disease, and we hope that the results from this study lead to improved outcomes for patients with pancreatic cancer.”
As of May 14, 2024, Verastem states that patients receiving this combination achieved a confirmed overall response rate (ORR) of 83% coming from 5 out of 6 patients. Upon the release of the results, the market responded positively boosting shares in the pharma company in pre-market trading. It should be noted that Verastem reported one dose-limiting toxicity of febrile neutropenia in the dose level 1 cohort, however the dose level was cleared after additional patients were enrolled in three other cohorts of the study.
“The initial interim results from the RAMP 205 trial evaluating avutometinib and defactinib in combination with standard of care first-line chemotherapy are encouraging and demonstrate the importance of targeting the RAS/MAPK pathway, as more than 90% of pancreatic tumors have a KRAS mutation,” said John Hayslip, M.D., Chief Medical Officer of Verastem Oncology. “We continue to progress the study evaluating other dose and schedule regimens to determine the recommended Phase 2 dose in the trial.”
Earlier in May, CytomX Therapeutics, Inc. (NASDAQ: CTMX) announced positive initial data from its ongoing Phase 1a dose escalation clinical study for its investigational, masked, conditionally activated PROBODY T-cell engager, CX-904, demonstrating a favorable safety profile and confirmed anti-cancer activity. Within the results, CytomX shared that 2 out of 6 patients (33%) showed a confirmed partial response, and all 6 patients (100%) with disease control in advanced pancreatic cancer.
“These data build on more than a decade of innovation at CytomX, and, we believe, open broad new possibilities for T-cell engagers across many targets and cancer types,” said Sean McCarthy, D.Phil., CEO and Chairman of CytomX. “We look forward to continuing to explore the potential of this exciting agent in multiple EGFR (epidermal growth factor receptor) positive cancers and to determining longer term strategy with our global development partner, Amgen.”
Three years after receiving the experimental cancer vaccine in a phase 1 trial from BioNTech SE (NASDAQ: BNTX), patients with pancreatic cancer continue to have T-cell responses. For 8 out of 16 patients with resected PDAC, BioNTech’s mRNA vaccine, autogene cevumeran, demonstrated persistence of T cells, which is associated with a longer median recurrence-free survival in cancer vaccine responders.
Currently, BioNTech is enrolling patients for a phase 2 trial of the therapy, autogene cevumeran, in combination with atezolizumab and chemotherapy, compared to modified FOLFIRINOX in PDAC patients.
“These new data are an early signal for the potential of our individualized mRNA cancer vaccine approach in this indication with an unmet medical need,” said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. “The results indicate that our uridine mRNA-LPX technology can promote activation of cytotoxic T cells that may help to eliminate residual tumor foci at early stages of the disease to delay or prevent recurrence.”
Later this year, FibroGen, Inc. (NASDAQ: FGEN) expects to deliver important topline data involving its potential first-in-class antibody pamrevlumab for two different types of pancreatic cancer.
“Looking ahead, we expect to report topline data from our two late-stage clinical trials of pamrevlumab in pancreatic cancer in the coming months,” said Thane Wettig, CEO of FibroGen. Among the upcoming milestones within FibroGen’s Q1 2024 financial results, the company said they expect to deliver topline data from the PanCAN Precision Promise Phase 2/3 study of pamrevlumab in metastatic pancreatic in mid-2024, and topline data from the LAPIS Phase 3 study of pamrevlumab in locally advanced unresectable pancreatic cancer (LAPC) in Q3 2024.
