A Phase Ib/II Study of Pepinemab in Combination with Avelumab in Advanced Non–Small Cell Lung Cancer

Shafique, Michael; Fisher, Terrence L.; Evans, Elizabeth E.; Leonard, John E.; Pastore, Desa Rae E.; Mallow, Crystal; Em, Smith; Mishra, Vikas; Schröder, Andreas; Chin, Kevin M.; Beck, J. Thaddeus; Baumgart, Megan; Govindan, Ramaswamy; Gabrail, Nashat; Spira, Alexander I.; Seetharamu, Nagashree; Lou, Yanyan; Mansfield, Aaron S.; Sanborn, Rachel E.; Goldman, Jonathan W.; Zauderer, Maurice

doi:10.1158/1078-0432.ccr-20-4792

Cited by 13 publications

(17 citation statements)

References 31 publications

(40 reference statements)

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“…The combination of camrelizumab and chemotherapy including carboplatin and pemetrexed could also ameliorate the mPFS (11 months) of NSCLC patients without EGFR and ALK mutations ( 184 ). More interestingly, in a phase Ib/II study ( NCT03268057 (first posted: 31 August 2017) ), pepinemab that mainly treats Alzheimer’s disease and Huntington’s disease in combination with avelumab (an anti-PD-L1 antibody) was proved well-tolerated in NSCLC patients ( 185 ). Even though the patients’ mPFS was only 8.4 weeks in this trial ( Table 3 ), this clinical study provides a new option for the treatment of NSCLC ( Figure 3 ).…”

Section: Treatments For Lung Cancermentioning

confidence: 99%

Current treatments for non-small cell lung cancer

et al. 2022

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Despite improved methods of diagnosis and the development of different treatments, mortality from lung cancer remains surprisingly high. Non-small cell lung cancer (NSCLC) accounts for the large majority of lung cancer cases. Therefore, it is important to review current methods of diagnosis and treatments of NSCLC in the clinic and preclinic. In this review, we describe, as a guide for clinicians, current diagnostic methods and therapies (such as chemotherapy, chemoradiotherapy, targeted therapy, antiangiogenic therapy, immunotherapy, and combination therapy) for NSCLC.

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Section: Treatments For Lung Cancermentioning

confidence: 99%

Current treatments for non-small cell lung cancer

et al. 2022

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“…This change in the tumor architecture was associated with durable tumor rejection in murine Colon26 and ERBB2(+) mammary carcinoma models (46). Recently, a Phase Ib/II study of pepinemab (anti-Sema4D) in combination with avelumab (anti-PD-L1) showed that the combination therapy was well tolerated and exerted antitumor activity in immunotherapy-resistant and PD-L1-low NSCLC patients (76). However, the function of Sema4D on Treg responses in cancer is still unknown.…”

Section: Sema4dmentioning

confidence: 99%

“…For instance, the combination of Sema4D mAb with either CTLA-4 or PD-1 inhibitor abrogates tumor growth in murine oral cancer-1 mice by inhibiting MDSC recruitment and enhances CTL infiltration (44). Recently, the combination of lgG mAb targeting Sema4D (pepinemab) with PD-L1 inhibitor avelumab has been evaluated as a safe and tolerated synthetic therapy in phase II clinical trials of immunotherapy-resistant NSCLC patients (76). Another phase I trial (NCT03425461) has been registered on ClinicalTrials.gov.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Semaphorins as Potential Immune Therapeutic Targets for Cancer

et al. 2022

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Semaphorins are a large class of secreted or membrane-bound molecules. It has been reported that semaphorins play important roles in regulating several hallmarks of cancer, including angiogenesis, metastasis, and immune evasion. Semaphorins and their receptors are widely expressed on tumor cells and immune cells. However, the biological role of semaphorins in tumor immune microenvironment is intricate. The dysregulation of semaphorins influences the recruitment and infiltration of immune cells, leading to abnormal anti-tumor effect. Although the underlying mechanisms of semaphorins on regulating tumor-infiltrating immune cell activation and functions are not fully understood, semaphorins can notably be promising immunotherapy targets for cancer.

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“…Although CD100 has been described as a costimulatory ligand for DETC, its role in cancer appears to be mostly pro-tumorigenic as demonstrated by the antitumor activity of blocking anti-CD100 antibodies in mouse tumor models [ 52 , 59 ]. Based on these studies, an antagonistic anti-human CD100 antibody (pepinemab) is currently being tested in phase II clinical trials for the treatment of human cancers [ 123 , 124 ]. If successful in clinical trials, the effect of blocking anti-CD100 antibodies on inhibition of pro-tumor IL-17-producing γδ T cells versus antitumor IFNγ-producing γδ T cells will be of interest and may help inform which solid tumor indications are most suitable for treatment [ 61 ].…”

Section: Introductionmentioning

confidence: 99%

γδ T cell costimulatory ligands in antitumor immunity

McGraw

Witherden

2022

Explor Immunol

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Antitumor immunity relies on the ability of T cells to recognize and kill tumor targets. γδ T cells are a specialized subset of T cells that predominantly localizes to non-lymphoid tissue such as the skin, gut, and lung where they are actively involved in tumor immunosurveillance. γδ T cells respond to self-stress ligands that are increased on many tumor cells, and these interactions provide costimulatory signals that promote their activation and cytotoxicity. This review will cover costimulatory molecules that are known to be critical for the function of γδ T cells with a specific focus on mouse dendritic epidermal T cells (DETC). DETC are a prototypic tissue-resident γδ T cell population with known roles in antitumor immunity and are therefore useful for identifying mechanisms that may control activation of other γδ T cell subsets within non-lymphoid tissues. This review concludes with a brief discussion on how γδ T cell costimulatory molecules can be targeted for improved cancer immunotherapy.

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A Phase Ib/II Study of Pepinemab in Combination with Avelumab in Advanced Non–Small Cell Lung Cancer

Abstract: biomarker analysis demonstrated improved tumoral infiltration of CD8+ T cells and supported the proposed mechanism of action of pepinemab, namely, to shift the tumor microenvironment toward immunity and away from immunosuppression thus enhancing immune checkpoint inhibition.Research.

Cited by 13 publications

References 31 publications

Current treatments for non-small cell lung cancer

Current treatments for non-small cell lung cancer

Semaphorins as Potential Immune Therapeutic Targets for Cancer

γδ T cell costimulatory ligands in antitumor immunity

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