Effect of anti-CTGF human recombinant monoclonal antibody pamrevlumab on resectability and resection rate when combined with gemcitabine/nab-paclitaxel in phase 1/2 clinical study for the treatment of locally advanced pancreatic cancer patients.

Picozzi, Vincent J.; Pishvaian, Michael J.; Mody, Kabir; Winter, Jordan M.; Glaspy, John A.; Larson, Tim; Matrana, Marc; Saikali, Khalil G.; Carney, Mairead; Porter, Seth; Yu, Peony; Kouchakji, Elias; Carrier, Ewa

doi:10.1200/jco.2018.36.15_suppl.4016

Cited by 17 publications

(8 citation statements)

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“…However, it was unclear whether the higher resectability among patients treated with pamrevlumab and chemotherapy was due to higher response rates or lower incidence of disease progression during the six cycles of treatment. Importantly, addition of pamrevlumab did not increase perioperative adverse events or delay in surgical wound healing[ 61 ]. A phase III trial is currently underway evaluating the safety and efficacy of pamrevlumab in combination with gemcitabine and nab-paclitaxel for patients with locally advanced PDAC (NCT03941093).…”

Section: Targeting Stroma-promoting Pathways In Pdac Cellsmentioning

confidence: 99%

Stroma-targeting strategies in pancreatic cancer: Past lessons, challenges and prospects

Polani¹,

Grierson²,

Lim³

2021

WJG

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Pancreatic ductal adenocarcinoma (PDAC) is projected to emerge as the second leading cause of cancer-related death after 2030. Extreme treatment resistance is perhaps the most significant factor that underlies the poor prognosis of PDAC. To date, combination chemotherapy remains the mainstay of treatment for most PDAC patients. Compared to other cancer types, treatment response of PDAC tumors to similar chemotherapy regimens is clearly much lower and shorter-lived. Aside from typically harboring genetic alterations that to date remain un-druggable and are drivers of treatment resistance, PDAC tumors are uniquely characterized by a densely fibrotic stroma that has well-established roles in promoting cancer progression and treatment resistance. However, emerging evidence also suggests that indiscriminate targeting and near complete depletion of stroma may promote PDAC aggressiveness and lead to detrimental outcomes. These conflicting results undoubtedly warrant the need for a more in-depth understanding of the heterogeneity of tumor stroma in order to develop modulatory strategies in favor of tumor suppression. The advent of novel techniques including single cell RNA sequencing and multiplex immunohistochemistry have further illuminated the complex heterogeneity of tumor cells, stromal fibroblasts, and immune cells. This new knowledge is instrumental for development of more refined therapeutic strategies that can ultimately defeat this disease. Here, we provide a concise review on lessons learned from past stroma-targeting strategies, new challenges revealed from recent preclinical and clinical studies, as well as new prospects in the treatment of PDAC.

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Section: Targeting Stroma-promoting Pathways In Pdac Cellsmentioning

confidence: 99%

Stroma-targeting strategies in pancreatic cancer: Past lessons, challenges and prospects

Polani¹,

Grierson²,

Lim³

2021

WJG

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“…The results showed that pamrevlumab was well tolerated with no dose-limiting toxicity or dose-related trends in the type or incidence of serious AEs. In a subsequent phase I/II study using gemcitabine/nab-paclitaxel with pamrevlumab or gemcitabine/nab-paclitaxel alone for patients with locally advanced PC, pamrevlumab combination arm showed a higher percentage of surgical resection (33.3% versus 7.7%) and improved median survival rate, plus the combination was feasible and well tolerated with no incremental safety signals (90). Accordingly, a phase III (LAPIS) trial is currently ongoing to investigate the efficacy of pamrevlumab plus gemcitabine with nabpaclitaxel in locally advanced, unresectable PC (NCT03941093).…”

Section: Connective Tissue Growth Factormentioning

confidence: 99%

Targeting the Stroma in the Management of Pancreatic Cancer

2021

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Pancreatic cancer (PC) presents extremely aggressive tumours and is associated with poor survival. This is attributed to the unique features of the tumour microenvironment (TME), which is known to create a dense stromal formation and poorly immunogenic condition. In particular, the TME of PC, including the stromal cells and extracellular matrix, plays an essential role in the progression and chemoresistance of PC. Consequently, several promising agents that target key components of the stroma have already been developed and are currently in multiple stages of clinical trials. Therefore, the authors review the latest available evidence on novel stroma-targeting approaches, highlighting the potential impact of the stroma as a key component of the TME in PC.

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“…The efficacy of pamrevlumab (FG-3019) against pancreatic tumors was further confirmed by another study that showed its effectiveness in selectively targeting pancreatic tumor cells and inhibiting metastases ( 101 ). In a phase I and II study, pamrevlumab, enhanced gemcitabine activity in locally advanced pancreatic cancer patients ( 102 ). Similarly, another study also demonstrated the use of peptides targeting CTGF alone and in combination with gemcitabine in reducing tumor size ( 103 ).…”

Section: Growth Factors and Chemoresistancementioning

confidence: 99%

Targeting Growth Factor Signaling Pathways in Pancreatic Cancer: Towards Inhibiting Chemoresistance

et al. 2021

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Pancreatic cancer is one of the most deadly cancers, ranking amongst the top leading cause of cancer related deaths in developed countries. Features such as dense stroma microenvironment, abnormal signaling pathways, and genetic heterogeneity of the tumors contribute to its chemoresistant characteristics. Amongst these features, growth factors have been observed to play crucial roles in cancer cell survival, progression, and chemoresistance. Here we review the role of the individual growth factors in pancreatic cancer chemoresistance. Importantly, the interplay between the tumor microenvironment and chemoresistance is explored in the context of pivotal role played by growth factors. We further describe current and future potential therapeutic targeting of these factors.

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Effect of anti-CTGF human recombinant monoclonal antibody pamrevlumab on resectability and resection rate when combined with gemcitabine/nab-paclitaxel in phase 1/2 clinical study for the treatment of locally advanced pancreatic cancer patients.

Cited by 17 publications

References 0 publications

Stroma-targeting strategies in pancreatic cancer: Past lessons, challenges and prospects

Stroma-targeting strategies in pancreatic cancer: Past lessons, challenges and prospects

Targeting the Stroma in the Management of Pancreatic Cancer

Targeting Growth Factor Signaling Pathways in Pancreatic Cancer: Towards Inhibiting Chemoresistance

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