Exploratory study of an anti-PD-L1/TGF-β antibody, TQB2858, in patients with refractory or recurrent osteosarcoma and alveolar soft part sarcoma: a report from Chinese sarcoma study group (TQB2858-Ib-02)
Abstract Background Novel and effective immunotherapies are required for refractory or recurrent sarcomas. Transforming growth factor-beta (TGF-β) is a diverse regulatory and fibrogenic protein expressed in multiple sarcoma tumors that promotes epithelial-mesenchymal transition and excessive deposit...
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-11390-4 |
| _version_ | 1797452325222088704 |
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| author | Lu Xie Xin Liang Jie Xu Xin Sun Kuisheng Liu Kunkun Sun Yuan Li Xiaodong Tang Xianan Li Xing Zhan Xiaohui Niu Wei Guo |
| author_facet | Lu Xie Xin Liang Jie Xu Xin Sun Kuisheng Liu Kunkun Sun Yuan Li Xiaodong Tang Xianan Li Xing Zhan Xiaohui Niu Wei Guo |
| author_sort | Lu Xie |
| collection | DOAJ |
| description | Abstract Background Novel and effective immunotherapies are required for refractory or recurrent sarcomas. Transforming growth factor-beta (TGF-β) is a diverse regulatory and fibrogenic protein expressed in multiple sarcoma tumors that promotes epithelial-mesenchymal transition and excessive deposition of extracellular matrix. This study evaluated the efficacy and safety of the anti-PD-L1/TGF-β antibody TQB2858 in patients with refractory osteosarcoma and alveolar soft part sarcoma (ASPS). Methods This single-arm phase 1b exploratory study included patients with refractory osteosarcoma or ASPS who had previously undergone at least two lines of systemic therapy. Patients were administered 1200 mg of TQB2858 once every 3 weeks. The primary endpoint was objective response rate (ORR), with null and alternative hypotheses of ORR ≤5% and ≥20%, respectively. Exploratory biomarker analyses using immunohistochemistry (IHC) staining (for PD-L1 and TGF-β) were performed on pre-treatment tumor samples. Results Eleven eligible patients were included in this study. TQB2858 did not demonstrate evidence of efficacy as 0/5 osteosarcomas had any objective response, while 2/6 ASPS showed a partial response. The median progression-free survivals were 1.51 (1.38, Not Evaluable) and 2.86 (1.38, Not Evaluable) months for the osteosarcoma and ASPS groups, respectively. None of the administered cycles met the criteria for unacceptable toxicity. Other Grade 3 toxicities included abnormal liver function and elevation of γ-glutamyl transferase. IHC analysis revealed that functional enrichment in the TGF-β pathway or PD-L1 was not associated with treatment outcomes. Conclusions The combination of PD-L1 and TQB2858 did not significantly improve the ORR in patients with recurrent osteosarcoma. However, it improved immunogenic responses in ASPS, even after progression upon anti-PD-1/PD-L1 therapy, with an acceptable safety profile. IHC profiling with pathway enrichment analysis may not have any predictive value for survival outcomes. Trial registration Prospectively registered in the Ethical Review Committee of Peking University People’s Hospital. The trial registration number is 2021PHA105-001 and 2021PHA140-001 and the registration date was March 2, 2022. ClinicalTrials.gov Identifier CTR20213001 and CTR20220390 |
| first_indexed | 2024-03-09T15:06:55Z |
| format | Article |
| id | doaj.art-a15bad3cad8749fcb9e000a820908431 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-09T15:06:55Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-a15bad3cad8749fcb9e000a8209084312023-11-26T13:36:11ZengBMCBMC Cancer1471-24072023-09-0123111110.1186/s12885-023-11390-4Exploratory study of an anti-PD-L1/TGF-β antibody, TQB2858, in patients with refractory or recurrent osteosarcoma and alveolar soft part sarcoma: a report from Chinese sarcoma study group (TQB2858-Ib-02)Lu Xie0Xin Liang1Jie Xu2Xin Sun3Kuisheng Liu4Kunkun Sun5Yuan Li6Xiaodong Tang7Xianan Li8Xing Zhan9Xiaohui Niu10Wei Guo11Musculoskeletal Tumor Center, Peking University People’s HospitalMusculoskeletal Tumor Center, Peking University People’s HospitalMusculoskeletal Tumor Center, Peking University People’s HospitalMusculoskeletal Tumor Center, Peking University People’s HospitalMusculoskeletal Tumor Center, Peking University People’s HospitalPathology Department, Peking University People’s HospitalRadiology Department and Nuclear Medicine Department, Peking University People’s HospitalMusculoskeletal Tumor Center, Peking University People’s HospitalOrthopedic Oncology Department, Hunan Cancer HospitalMedical Oncology, Sun Yat-sen University Cancer CenterOrthopedic Oncology Department, Beijing Jishuitan HospitalMusculoskeletal Tumor Center, Peking University People’s HospitalAbstract Background Novel and effective immunotherapies are required for refractory or recurrent sarcomas. Transforming growth factor-beta (TGF-β) is a diverse regulatory and fibrogenic protein expressed in multiple sarcoma tumors that promotes epithelial-mesenchymal transition and excessive deposition of extracellular matrix. This study evaluated the efficacy and safety of the anti-PD-L1/TGF-β antibody TQB2858 in patients with refractory osteosarcoma and alveolar soft part sarcoma (ASPS). Methods This single-arm phase 1b exploratory study included patients with refractory osteosarcoma or ASPS who had previously undergone at least two lines of systemic therapy. Patients were administered 1200 mg of TQB2858 once every 3 weeks. The primary endpoint was objective response rate (ORR), with null and alternative hypotheses of ORR ≤5% and ≥20%, respectively. Exploratory biomarker analyses using immunohistochemistry (IHC) staining (for PD-L1 and TGF-β) were performed on pre-treatment tumor samples. Results Eleven eligible patients were included in this study. TQB2858 did not demonstrate evidence of efficacy as 0/5 osteosarcomas had any objective response, while 2/6 ASPS showed a partial response. The median progression-free survivals were 1.51 (1.38, Not Evaluable) and 2.86 (1.38, Not Evaluable) months for the osteosarcoma and ASPS groups, respectively. None of the administered cycles met the criteria for unacceptable toxicity. Other Grade 3 toxicities included abnormal liver function and elevation of γ-glutamyl transferase. IHC analysis revealed that functional enrichment in the TGF-β pathway or PD-L1 was not associated with treatment outcomes. Conclusions The combination of PD-L1 and TQB2858 did not significantly improve the ORR in patients with recurrent osteosarcoma. However, it improved immunogenic responses in ASPS, even after progression upon anti-PD-1/PD-L1 therapy, with an acceptable safety profile. IHC profiling with pathway enrichment analysis may not have any predictive value for survival outcomes. Trial registration Prospectively registered in the Ethical Review Committee of Peking University People’s Hospital. The trial registration number is 2021PHA105-001 and 2021PHA140-001 and the registration date was March 2, 2022. ClinicalTrials.gov Identifier CTR20213001 and CTR20220390https://doi.org/10.1186/s12885-023-11390-4PD-L1/TGF-βAlveolar Soft Part Sarcoma (ASPS)OsteosarcomaTumor immune microenvironment |
| spellingShingle | Lu Xie Xin Liang Jie Xu Xin Sun Kuisheng Liu Kunkun Sun Yuan Li Xiaodong Tang Xianan Li Xing Zhan Xiaohui Niu Wei Guo Exploratory study of an anti-PD-L1/TGF-β antibody, TQB2858, in patients with refractory or recurrent osteosarcoma and alveolar soft part sarcoma: a report from Chinese sarcoma study group (TQB2858-Ib-02) BMC Cancer PD-L1/TGF-β Alveolar Soft Part Sarcoma (ASPS) Osteosarcoma Tumor immune microenvironment |
| title | Exploratory study of an anti-PD-L1/TGF-β antibody, TQB2858, in patients with refractory or recurrent osteosarcoma and alveolar soft part sarcoma: a report from Chinese sarcoma study group (TQB2858-Ib-02) |
| title_full | Exploratory study of an anti-PD-L1/TGF-β antibody, TQB2858, in patients with refractory or recurrent osteosarcoma and alveolar soft part sarcoma: a report from Chinese sarcoma study group (TQB2858-Ib-02) |
| title_fullStr | Exploratory study of an anti-PD-L1/TGF-β antibody, TQB2858, in patients with refractory or recurrent osteosarcoma and alveolar soft part sarcoma: a report from Chinese sarcoma study group (TQB2858-Ib-02) |
| title_full_unstemmed | Exploratory study of an anti-PD-L1/TGF-β antibody, TQB2858, in patients with refractory or recurrent osteosarcoma and alveolar soft part sarcoma: a report from Chinese sarcoma study group (TQB2858-Ib-02) |
| title_short | Exploratory study of an anti-PD-L1/TGF-β antibody, TQB2858, in patients with refractory or recurrent osteosarcoma and alveolar soft part sarcoma: a report from Chinese sarcoma study group (TQB2858-Ib-02) |
| title_sort | exploratory study of an anti pd l1 tgf β antibody tqb2858 in patients with refractory or recurrent osteosarcoma and alveolar soft part sarcoma a report from chinese sarcoma study group tqb2858 ib 02 |
| topic | PD-L1/TGF-β Alveolar Soft Part Sarcoma (ASPS) Osteosarcoma Tumor immune microenvironment |
| url | https://doi.org/10.1186/s12885-023-11390-4 |
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