Pancreatic Cancer Highlights: ASCO 2021

With ASCO 2021 kicking off at full speed, there is a lot to take in, ranging from cutting-edge clinical trials, approvals, and investments in the Pancreatic Cancer domain, as demonstrated by the abstract presentation at ASCO21. Have a read of DelveInsight’s SMEs take on the same. 

Abstract Number: 4144: PDAC: Oncolytics Biotech/Merck

On 4th June 2021, Oncolytics and Merck have presented Phase II safety, and efficacy results with pembrolizumab in combination with the oncolytic virus (pelareorep) promotes anti-tumor immunity in patients with advanced pancreatic adenocarcinoma for pancreatic ductal adenocarcinoma (PDAC).

Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease, mostly due to late diagnosis, aggressive growth, and therapy resistance. Nearly 95 out of 100 (95%) of all pancreatic cancers are PDAC. The company is exploring pembrolizumab in combination with pelareorep work in treating patients with pancreatic cancer that has spread to other parts of the body.

The study has shown that nearly 33% of the 12 efficacy-evaluable patients had achieved disease control. One patient achieved a partial response (PR). Three additional patients achieved stable disease (SD). On-treatment tumor biopsies, collected during C1, showed pelareorep replication, increased infiltration of CD8+ T cells and PD-L1+ cells, and decreased expression of VDAC1, a mitochondrial gatekeeper for tumor promotion, relative to archival tissue. Reduced infiltration of Foxp3+ regulatory T cells (Treg) was observed in patients showing tumor response. Peripheral blood was collected on day 1 of each cycle and on C1 day 8. Relative to pretreatment samples, the number of CD8+ effector memory T cells and B cells tend to increase while the number of Treg cells declined in C2 onwards in patients with tumor response. Furthermore, these patients had increased expression of the mitochondrial protein TOMM20 in CD8+ T cells and decreased expression of PD-1 and the H3K27me3 epigenetic mark in Treg. Treatment was well tolerated, with most treatment-related adverse events being grade 1 or 2.

Expert Views “The combination of pelareorep and pembrolizumab showed a manageable safety profile and modest efficacy in an unselected PDAC population. In the efficacy results, both disease control and overall survival are also consistent with prior studies in second-line PDAC patients despite the absence of chemotherapy in the study.”

Abstract Number: 4018: Pancreatic Cancer: AB Science

On 4th June 2021, AB science presented Phase III results for MAS in combination with gemcitabine (GEM) to improve overall survival (OS) in pancreatic cancer (PC) patients with pain.

The study has enrolled 384 patients. In the predefined subgroup of unresectable LAPC with pain, MAS-GEM (n = 62) showed significant benefit over PBO-GEM (n = 30) with a median OS of 13.0 months vs 11.2 months. The HR was 0.46, corresponding to a significant 54% reduction in risk of death for MAS-GEM patients relative to control. Secondary analyses in the same subgroup were convergent with this primary outcome. Median PFS showed a 1.8-month between-group difference in favor of MAS-GEM. The 12-month and 18-month OS rates showed a 1.3 fold and 3.4 fold improvement, respectively, in favor of MAS-GEM (53.2% and 33.9% for MAS-GEM vs 40.0% and 10% for PBO-GEM, respectively). In the overall population, comprising LAPC and mPC patients with pain, no survival benefit was observed; median OS for MAS-GEM (n = 244) was 6.9 months vs 8.0 months for PBO-GEM (n = 135). The MAS-GEM combination was well tolerated with no sign of add-on toxicity. 

Expert Views “The combination MAS plus GEM may provide a new first-line treatment option for unresectable LAPC patients with associated pain. MAS plus GEM confers a meaningful overall survival benefit (+1.8 months, significant 54% reduced risk of death) in unresectable locally advanced pancreatic cancer patients with pain. Furthermore, PFS and response rate were consistent with OS results.

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