A Multi-Center Phase IIA Trial to Assess the Safety and Efficacy of BL-8040 (a CXCR4 Inhibitor) in Combination with Pembrolizumab and Chemotherapy in Patients with Metastatic Pancreatic Adenocarcinoma (PDAC)

Hidalgo, Manuel; Semenisty, Valerya; Bockorny, Bruno; Borazanci, Erkut; Hoff, Daniel D. Von; Feliú, Jaime; Sarvise, M. Ponz; Abad, David Gutiérrez; Peled, Amnon; Bohana‐Kashtan, Osnat; Gozlan, Yosi; Sorani, Ella; Chaney, Marya; Kadosh, Shaul; Vainstein, Abi; Macarulla, Teresa

doi:10.1093/annonc/mdz451

Cited by 11 publications

(6 citation statements)

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“…The COMBAT/KEYNOTE‐202 trial is an ongoing phase II study evaluating BL‐8040, a CXCR4 inhibitor, with pembrolizumab and chemotherapy in patients with metastatic pancreatic cancer (ClinicalTrials.gov; NCT02826486). Thus far, preliminary data from this trial shows promising rates of disease control (12 of 15 evaluable patients) 67 …”

Section: Stromal Landscape Of Pancreatic Cancermentioning

confidence: 88%

“…Thus far, preliminary data from this trial shows promising rates of disease control (12 of 15 evaluable patients). 67 The CCR2/CCL2 axis is also an attractive therapeutic target in conjunction with immunotherapy. As described above, the production of CCL2 by pancreatic cancer facilitates the mobilization of inflammatory monocytes from the bone marrow into the peripheral blood and the recruitment of immunosuppressive CCR2+…”

Section: Targeting Stroma To Improve Immunotherapy Efficacymentioning

confidence: 99%

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Understanding the immune landscape and tumor microenvironment of pancreatic cancer to improve immunotherapy

Torphy

Schulick

Zhu

2020

Molecular Carcinogenesis

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Immunotherapy has revolutionized cancer treatment for several hematologic and solid organ malignancies; however, pancreatic cancer remains unresponsive to conventional immunotherapies. Several characteristics of pancreatic cancer present challenges to successful treatment with immunotherapy, including its aggressive biology, poor immunogenicity, and abundant desmoplastic stroma which can impede effector T cell infiltration and promote an immunosuppressive microenvironment.In this review, we evaluate the current understanding of the immune and stromal landscapes of pancreatic cancer, discuss the successes and failures of stromatargeted therapies, and highlight how stroma-directed therapies may be synergistic with immunotherapy. K E Y W O R D S desmoplasia, immunotherapy, pancreatic ductal adenocarcinoma, stroma 1 | INTRODUCTION Cancer immunosurveillance is the concept that the immune system can identify and kill tumors and is based on the foundational principle that T cells can identify and kill cancer cells with unique or foreign antigens. 1 The concept of cancer immunosurveillance was further refined to the theory of cancer immunoediting based on the understanding that the immune system can act to protect a host from tumor development, but also is capable of promoting tumor growth. 2 The field of cancer immunotherapy focuses on unleashing the ability of the host's immune system to eliminate tumors through disrupting immunosuppressive signals with immune checkpoint blockade, enhancing tumor-specific T cell activity through adoptive T cell therapy, and improving antitumor T cell education with vaccines. Chimeric antigen receptor (CAR) T cell therapies are now successfully being used to treat several hematological malignancies. 3,4 Some solid organ malignancies are also now effectively being treated using immunotherapy as immune checkpoint blockade has revolutionized the field of immunotherapy over the past decade. 5,6Despite the success of immune checkpoint blockade in treating several solid organ malignancies, pancreatic cancer remains unresponsive to conventional immunotherapies. 7,8 Pancreatic ductal adenocarcinoma, which comprises well over 90% of pancreatic cancers and is estimated to be the third leading cause of cancer-related deaths in the United States in 2020 has several unique characteristics which present challenges to successful treatment with immunotherapy. 9 Pancreatic cancer often presents at a very late stage, with only 20% of the patients diagnosed with surgically resectable disease, which currently is the only potentially curative treatment. This late presentation, in conjunction with the aggressive biology of this disease, leads to patients often being diagnosed with metastatic disease and poor overall survival rates. 10 Secondly, pancreatic cancer is often described as an immunologically cold cancer with relatively few neoantigens to be recognized by immune cells.Lastly, pancreatic cancer has a characteristic desmoplastic stromal

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Section: Stromal Landscape Of Pancreatic Cancermentioning

confidence: 88%

Section: Targeting Stroma To Improve Immunotherapy Efficacymentioning

confidence: 99%

Understanding the immune landscape and tumor microenvironment of pancreatic cancer to improve immunotherapy

Torphy

Schulick

Zhu

2020

Molecular Carcinogenesis

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“…Additional ablation ameliorated effectiveness with acceptable toxicity, and the RR rose from 10 to 24% (12/50). The median time to progression (MTP), PFS, and OS was 6.1, 5, and 16.9 months, respectively (68).…”

Section: Immune Checkpoint Inhibitors In Localized Hccmentioning

confidence: 99%

Immune Checkpoint Inhibitors in the Treatment of HCC

et al. 2021

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Hepatocellular carcinoma (HCC) is the typical inflammation-induced neoplasia. It often prospers where a chronic liver disease persists, thus leading a strong rationale for immune therapy. Several immune-based treatments, including immune checkpoint inhibitors (ICI), cytokines, adoptive cell transfer, and vaccines, have been tested in the treatment of HCC. In this review, we summarize the role of the ICI in HCC patients in various sets of treatment. As for advanced HCC, the anti-Programmed cell Death protein 1 (PD1) antibodies and the anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) antibodies have been examined in patients with enthusiastic results in phase I-II-III studies. Overall, this led the Food and Drug Administration (FDA) to approve pembrolizumab, nivolumab, and nivolumab + ipilimumab in the second-line setting. The anti- Programmed Death-Ligand 1 (PDL-1) antibodies have also been evaluated. Thanks to the results obtained from phase III IMbrave study, atezolizumab + bevacizumab is now the standard of care in the first-line advanced setting of HCC. As for localized HCC, the putative immunological effect of locoregional therapies led to evaluate the combination strategy with ICI. This way, chemoembolization, ablation with radiofrequency, and radioembolization combined with ICI are currently under study. Likewise, the study of adjuvant immunotherapy following surgical resection is underway. In addition, the different ICI has been studied in combination with other ICI as well as with multikinase inhibitors and anti-angiogenesis monoclonal antibody. The evidence available suggests that combining systemic therapies and locoregional treatments with ICI may represent an effective strategy in this context.

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“…Для прерывания передачи сигнала через иммунную контрольную точку PD-1 используются 2 класса препаратов, схожих по действию: ингибиторы рецептора PD-1 Таблица 2. Сравнение популяций MIRACULUM и аналогичных исследований [11][12][13] Table 2. Comparison of mIRACuLum and similar studies populations [11][12][13]…”

Section: Immunotherapy In Oncologyunclassified

“…Сравнение популяций MIRACULUM и аналогичных исследований [11][12][13] Table 2. Comparison of mIRACuLum and similar studies populations [11][12][13]…”

Section: Immunotherapy In Oncologyunclassified

inhibitor prolgolimab in metastatic skin melanoma: recent data and experience of use

Редакционная¹

2021

Medicinskij sovet

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A Multi-Center Phase IIA Trial to Assess the Safety and Efficacy of BL-8040 (a CXCR4 Inhibitor) in Combination with Pembrolizumab and Chemotherapy in Patients with Metastatic Pancreatic Adenocarcinoma (PDAC)

Cited by 11 publications

References 0 publications

Understanding the immune landscape and tumor microenvironment of pancreatic cancer to improve immunotherapy

Understanding the immune landscape and tumor microenvironment of pancreatic cancer to improve immunotherapy

Immune Checkpoint Inhibitors in the Treatment of HCC

inhibitor prolgolimab in metastatic skin melanoma: recent data and experience of use

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