Efficacy and Safety of TRC105 Plus Pazopanib vs Pazopanib Alone for Treatment of Patients With Advanced Angiosarcoma

Jones, Robin L.; Ravi, Vinod; Brohl, Andrew S.; Chawla, Sant P.; Ganjoo, Kristen N.; Italiano, Antoîne; Burgess, Melissa; Thornton, Katherine A.; Cranmer, Lee D.; Cheang, Maggie C.U.; Liu, Lingyun; Robertson, Liz; Adams, Bonne J.; Theuer, Charles P.; Maki, Robert G.

doi:10.1001/jamaoncol.2021.3547

Cited by 27 publications

(19 citation statements)

References 25 publications

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“…This is of less concern as various studies that exploited CD105 for therapeutic applications reported little to no adverse effects (38,48). Similarly, the monoclonal antibody TRC105 was well-tolerated in monotherapy and combination therapy in clinical trials (53,54). Here, we confirmed that this CTL-based therapy against CD105 did not impact the wound- healing capacities of the mice, nor did it affect the overall health of experimental mice (Figure 8).…”

Section: Discussionsupporting

confidence: 73%

Listeria-based immunotherapy directed against CD105 exerts anti-angiogenic and anti-tumor efficacy in renal cell carcinoma

et al. 2022

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Targeting tumor-associated angiogenesis is currently at the forefront of renal cell carcinoma (RCC) therapy, with sunitinib and bevacizumab leading to increased survival in patients with metastatic RCC (mRCC). However, resistance often occurs shortly after initiation of therapy, suggesting that targeting the tumor-associated vascular endothelium may not be sufficient to eradicate RCC. This study reports the therapeutic efficacy of a Listeria (Lm)-based vaccine encoding an antigenic fragment of CD105 (Lm-LLO-CD105A) that targets both RCC tumor cells and the tumor-associated vasculature. Lm-LLO-CD105A treatment reduced primary tumor growth in both subcutaneous and orthotopic models of murine RCC. The vaccine conferred anti-tumor immunity and remodeled the tumor microenvironment (TME), resulting in increased infiltration of polyfunctional CD8+ and CD4+ T cells and reduced infiltration of immunosuppressive cell types within the TME. We further provide evidence that the therapeutic efficacy of Lm-LLO-CD105A is mediated by CD8+ T cells and is dependent on the robust antigenic expression of CD105 by RCC tumor cells. The result from this study demonstrates the safety and promising therapeutic efficacy of targeting RCC-associated CD105 expression with Lm-based immunotherapy.

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Section: Discussionsupporting

confidence: 73%

Listeria-based immunotherapy directed against CD105 exerts anti-angiogenic and anti-tumor efficacy in renal cell carcinoma

et al. 2022

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“…A recent multicenter, phase 2 study evaluating pazopanib for uncurable angiosarcoma reported median PFS of 14.4 weeks and 3‐month PFS of 54.6% (95% CI 36.0–82.9%) 18 . In another clinical trial, the median PFS was 4.3 months with pazopanib for chemotherapy‐resistant angiosarcoma 19 . The median PFS was 132 days (4.4 months) in the present study, suggesting that the efficacy of pazopanib is comparable to that seen in previous clinical studies, even in a Japanese cohort 18,19 .…”

Section: Discussionmentioning

confidence: 99%

Treatment for taxane‐resistant cutaneous angiosarcoma: A multicenter study of 50 Japanese cases

Fujimura

Maekawa

Katô

et al. 2023

The Journal of Dermatology

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Cutaneous angiosarcoma (CAS) is a rare and highly aggressive type of vascular tumor. Although chemoradiotherapy with taxanes is recognized as a first‐line therapy for CAS, second‐line therapy for CAS remains controversial. From the above findings, the efficacy and safety profiles of taxane‐switch (change paclitaxel to docetaxel or vise), eribulin methylate, and pazopanib regimens in second‐line chemotherapy were evaluated retrospectively in 50 Japanese taxane‐resistant CAS patients. Although there was no significant difference in progression‐free survival (P = 0.3528) among the regimens, the incidence of all adverse events (AEs) (P = 0.0386), as well as severe G3 or more AEs (P = 0.0477) was significantly higher in the eribulin methylate group and pazopanib group than in the taxane‐switch group. The present data suggest that switching to another taxane should be considered for the treatment of taxane‐resistant CAS in second‐line therapy based on the safety profiles.

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“…In March 2022 the TAPPAS trial a phase 3, multinational, multicentre, open label, parallel group trial reported the efficacy and safety of TRC105 (carotuximab, an IgG1 antibody binding to endoglin) combined with pazopanib compared to treatment with pazopanib alone in patients with advanced angiosarcoma (89). However, the results were disappointing whilst the PFS (primary endpoint) was not improved with treatment with carotuximab combined with pazopanib compared to pazopanib alone.…”

Section: Combinations Of Immune Checkpoint Inhibitors With Targeted T...mentioning

confidence: 99%

Exploring the landscape of immunotherapy approaches in sarcomas

Pilavaki

Panagi²,

Arifi³

et al. 2023

Front. Oncol.

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Sarcomas comprise a heterogenous group of malignancies, of more than 100 different entities, arising from mesenchymal tissue, and accounting for 1% of adult malignancies. Surgery, radiotherapy and systemic therapy constitute the therapeutic armamentarium against sarcomas, with surgical excision and conventional chemotherapy, remaining the mainstay of treatment for local and advanced disease, respectively. The prognosis for patients with metastatic disease is dismal and novel therapeutic approaches are urgently required to improve survival outcomes. Immunotherapy, is a rapidly evolving field in oncology, which has been successfully applied in multiple cancers to date. Immunomodulating antibodies, adoptive cellular therapy, cancer vaccines, and cytokines have been tested in patients with different types of sarcomas through clinical trials, pilot studies, retrospective and prospective studies. The results of these studies regarding the efficacy of different types of immunotherapies in sarcomas are conflicting, and the application of immunotherapy in daily clinical practice remains limited. Additional clinical studies are ongoing in an effort to delineate the role of immunotherapy in patients with specific sarcoma subtypes.

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Efficacy and Safety of TRC105 Plus Pazopanib vs Pazopanib Alone for Treatment of Patients With Advanced Angiosarcoma

Abstract: This randomized clinical trial investigates whether carotuximab plus pazopanib improves progression-free survival vs pazopanib alone in adult patients with advanced angiosarcoma.

Cited by 27 publications

References 25 publications

Listeria-based immunotherapy directed against CD105 exerts anti-angiogenic and anti-tumor efficacy in renal cell carcinoma

Listeria-based immunotherapy directed against CD105 exerts anti-angiogenic and anti-tumor efficacy in renal cell carcinoma

Treatment for taxane‐resistant cutaneous angiosarcoma: A multicenter study of 50 Japanese cases

Exploring the landscape of immunotherapy approaches in sarcomas

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