[Translation] A Phase II/III study of the safety and efficacy of BAT1308 combined with platinum-based chemotherapy ± bevacizumab as a first-line treatment for PD-L1-positive (CPS ≥ 1) persistent, recurrent or metastatic cervical cancer

II期研究： BAT1308联合含铂化疗 ±贝伐珠单抗安全性和初步疗效研究主要目的：评价BAT1308联合含铂化疗±贝伐珠单抗一线治疗PD-L1阳性（CPS≥1）的持续、复发或转移性宫颈癌患者的安全性 III期研究： BAT1308联合含铂化疗 ±贝伐珠单抗用于一线治疗 PD-L1阳性（ CPS≥1）的持续、复发或转移性宫颈癌的安全性和有效性确证性研究主要目的：评价BAT1308联合含铂化疗±贝伐珠单抗对比含铂化疗±贝伐珠单抗一线治疗PD-L1阳性（CPS≥1）的持续、复发或转移性宫颈癌的有效性。

[Translation]

Phase II study: Safety and preliminary efficacy study of BAT1308 combined with platinum-containing chemotherapy ± bevacizumab Main purpose: To evaluate the safety of BAT1308 combined with platinum-containing chemotherapy ± bevacizumab as first-line treatment for patients with persistent, recurrent or metastatic cervical cancer with PD-L1 positive (CPS≥1) Phase III study: Safety and efficacy confirmation study of BAT1308 combined with platinum-containing chemotherapy ± bevacizumab as first-line treatment for persistent, recurrent or metastatic cervical cancer with PD-L1 positive (CPS≥1) Main purpose: To evaluate the efficacy of BAT1308 combined with platinum-containing chemotherapy ± bevacizumab versus platinum-containing chemotherapy ± bevacizumab as first-line treatment for persistent, recurrent or metastatic cervical cancer with PD-L1 positive (CPS≥1)

Start Date01 Dec 2023

Sponsor / Collaborator

Bio-Thera Solutions, Ltd.

NCT06123884 / Not yet recruitingPhase 2/3

A Phase II/III Study to Evaluate the Safety and Efficacy of BAT1308 Combined With Platinum-Based Chemotherapy ± Bevacizumab as First-Line Therapy For PD-L1-Positive (CPS ≥ 1) Persistent, Recurrent or Metastatic Cervical Cancer

Phase II study: a study to explore the safety and preliminary efficacy of BAT1308 combined with platinum-based chemotherapy ± Bevacizumab Phase III study: a confirmatory study to evaluate the safety and efficacy of BAT1308 combined with platinum-based chemotherapy ± Bevacizumab as first-line therapy for PD-L1-positive (CPS ≥ 1) persistent, recurrent or metastatic cervical cancer

Start Date01 Nov 2023

Sponsor / Collaborator

Bio-Thera Solutions, Ltd.

NCT05715840 / Not yet recruitingPhase 3

A Randomised, Double-blind, Placebo-controlled, Multicentre Phase Ш Clinical Study to Evaluate the Efficacy and Safety of First-line Treatment With SG001 Plus Chemotherapy±Bevacizumab Versus Placebo Plus Chemotherapy±Bevacizumab for PD-L1 Positive (CPS≥1) Women With Recurrent, or Metastatic Cervical Cancer

This study is a randomised, double-blind, placebo-controlled, multicentre phase 3 clinical study to evaluate the efficacy and safety of SG001 plus chemotherapy±bevacizumab versus placebo plus chemotherapy±bevacizumab, as first-line treatment, in patients with PD-L1 positive (CPS≥1), Recurrent or Metastatic Cervical Cancer. The study contains a Safety Lead-in Phase in which the safety and tolerability of SG001＋Chemotherapy±Bevacizumab will be assessed prior to the Phase 3 portion of the study.

Start Date31 Jan 2023

Sponsor / Collaborator

CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co., Ltd.

100 Clinical Results associated with PD-L1 positive Uterine Cervical Cancer

100 Translational Medicine associated with PD-L1 positive Uterine Cervical Cancer

0 Patents (Medical) associated with PD-L1 positive Uterine Cervical Cancer

Literatures (Medical) associated with PD-L1 positive Uterine Cervical Cancer

01 Dec 2024·Gynecologic Oncology

Phase II study of enlonstobart (SG001), a novel PD-1 inhibitor in patients with PD-L1 positive recurrent/metastatic cervical cancer

Article

Author: Xiang, Silong ; Ruan, Xiaohong ; Yin, Rutie ; Zuo, Jing ; Li, Guiling ; Li, Xiumin ; Wu, Lingying ; Hao, Deshun ; Liu, Hu ; Wei, Shuqing ; Lin, Daren ; Jiang, Kui ; Niu, Miao ; Feng, Mei ; Kang, Shan ; Chen, Ying ; Wang, Yili ; Li, Xiaofan ; Sun, Li ; Zhang, Yunyan ; Sun, Hongmei ; Zhu, Zhitu ; Wang, Wei

BACKGROUNDPlatinum-based chemotherapy with or without bevacizumab is the first-line treatment for patients with recurrent or metastatic cervical cancer (r/mCC), and the treatment options are limited for r/mCC after first-line treatment. Enlonstobart (SG001) is a fully humanized and high-affinity anti-PD-1 immunoglobulin G4 monoclonal antibody. Previous phase Ib study demonstrated that SG001 had a promising efficacy in patients with PD-L1 positive r/mCC.METHODSIn this multicenter, single-arm, open-label, phase II study, eligible patients were ≥ 18 years with PD-L1-positive cervical cancer who had progression on or intolerance to the first-line platinum-based chemotherapy. Patients received SG001 240 mg every two weeks for 24 months or until disease progression, intolerable toxicities, or other study discontinuation criteria were met. The primary endpoint was confirmed objective response rate (ORR) assessed by RECIST version 1.1 by independent review committee.RESULTS107 patients were enrolled with median age of 53 years (range 26-72). 64.5 % of patients had a ECOG of 1. After a median follow-up of 14.0 months (range 0.4-21.9), confirmed ORR was 29.0 %, with two complete responses and twenty-nine partial responses. The disease control rate was 54.2 %. Median duration of response was 16.6 months (95 % CI 10.8-NA), median progression free survival was 3.1 months (95 % CI 2.2-6.9). Median overall survival was not reached. 104 patients (97.2 %) experienced at least one treatment emergent adverse events TEAEs, of which 38 patients (35.5 %) had grade 3 or higher TEAEs. The most common treatment-related adverse events were leukopenia (19.6 %), increased aspartate aminotransferase (18.7 %), anemia (17.8 %), increased alanine aminotransferase (15.9 %), hypothyroidism (15.0 %), neutropenia (15.0 %), and hyperthyroidism (11.2 %).CONCLUSIONSG001 monotherapy demonstrated durable anti-tumor activity with acceptable safety in patients with PD-L1 positive r/mCC with progression on or intolerance to the first-line platinum-based chemotherapy.TRIAL REGISTRATIONClinicalTrials.gov (NCT04886700).

01 Aug 2024·International Journal of Gynecologic Cancer

A non-comparative, randomized, phase II trial of atezolizumab or atezolizumab plus tiragolumab for programmed death-ligand 1-positive recurrent cervical cancer (SKYSCRAPER-04)

Article

Author: Castro, Marcela ; Guzman Ramirez, Adrian ; Barraclough, Lisa ; Lorusso, Domenica ; Lin, Yvonne G ; McCormack, Mary ; Monk, Bradley J ; Gilbert, Lucy ; Hu, Youyou ; Kim, Nicole ; Molinero, Luciana ; Sabatier, Renaud ; Kim, Yong-Man ; Colombo, Nicoletta ; Ghamande, Sharad ; Lu, Chien-Hsing ; Krishnan, Venkatesh ; Feng, Yuning ; Hall, Shaundra L ; Salani, Ritu

ObjectiveTo evaluate tiragolumab (anti-TIGIT) and atezolizumab (anti-PD-L1) as second- or third-line therapy for PD-L1-positive persistent/recurrent cervical cancer.Methods In the open-label, non-comparative, randomized phase II SKYSCRAPER-04 trial ( NCT04300647 ), patients with PD-L1-positive (SP263 tumor area positivity ≥5%) recurrent/persistent cervical cancer after 1–2 chemotherapy lines (≥1 platinum-based) were randomized 3:1 to atezolizumab 1200 mg with/without tiragolumab 600 mg every 3 weeks until disease progression or unacceptable toxicity. Stratification factors were performance status, prior (chemo)radiotherapy, and disease status. The primary endpoint was independent review committee-assessed confirmed objective response rate per RECIST v1.1 in patients receiving tiragolumab plus atezolizumab. An objective response rate ≥21% (one-sample z-test p≤0.0245) was required for statistical significance versus a historical reference. Results Protocol-defined independent review committee-assessed objective response rates were 19.0% (95% CI 12.6 to 27.0) in 126 patients receiving tiragolumab plus atezolizumab (p=0.0787 vs historical reference) and 15.6% (95% CI 6.5 to 29.5) in 45 atezolizumab-treated patients. Response rates were higher in PD-L1 high (tumor area positivity ≥10%) than PD-L1 low (tumor area positivity 5%–9%) subgroups with both regimens. At 8.5 months’ median follow-up, independent review committee-assessed progression-free survival was 2.8 months (95% CI 1.7 to 4.1) with tiragolumab plus atezolizumab and 1.9 months (95% CI 1.5 to 3.0) with atezolizumab. In post hoc analyses (10.4 months’ median follow-up), median overall survival was 11.1 months (95% CI 9.6 to 14.5) with the combination and 10.6 months (95% CI 6.9 to 13.8) with atezolizumab (crossover permitted). In the combination group, 3% of patients had adverse events requiring treatment discontinuation and 8% had grade ≥3 adverse events of special interest; corresponding values in the single-agent arm were 4% and 11%. There were no treatment-related deaths or new safety findings. ConclusionThe objective response rate with the tiragolumab-plus-atezolizumab combination was numerically higher than the historical reference but did not reach statistical significance.

01 Dec 2023·The Lancet Oncology

Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial

Article

Author: Zhou, Qi ; Rey, Felipe ; Oppermann Kussler, Christina ; Mahantshetty, Umesh ; Tarnawski, Rafal ; Monk, Bradley J ; Cheng, Wen-Fang ; Sulay, Raymond ; Lee, Jung-Yun ; Shapira-Frommer, Ronnie ; Valdiviezo, Natalia ; Leiva, Manuel ; Kreynina, Yulia ; Varga, Szilvia ; Wildsmith, Sophie ; Mandai, Masaki ; Vázquez Limón, Juan C ; Aoki, Daisuke ; Tablante Nunes, Ana ; Limaye, Sewanti ; Toita, Takafumi ; Rong, Yi ; Wu, Xiaohua ; Godinez, Francisco J Ramirez ; Ke, Guihao ; Lloyd, Andrew ; Dry, Hannah ; Mayadev, Jyoti ; Del Pilar Estevez-Diz, Maria

BACKGROUNDConcurrent chemoradiotherapy has been the standard of care for locally advanced cervical cancer for over 20 years; however, 30-40% of treated patients have recurrence or progression within 5 years. Immune checkpoint inhibition has improved outcomes for patients with PD-L1 positive metastatic or recurrent cervical cancer. We assessed the benefit of adding durvalumab, a PD-L1 antibody, with and following chemoradiotherapy for locally advanced cervical cancer.METHODSThe CALLA randomised, double-blind, phase 3 trial included 105 hospitals across 15 countries. Patients aged at least 18 years with previously untreated locally advanced cervical cancer (adenocarcinoma, squamous, or adenosquamous; International Federation of Gynaecology and Obstetrics [FIGO] 2009 stage IB2-IIB lymph node positive, stage ≥III any lymph node status) and WHO or Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) through an interactive web response system using a permuted block size of 4 to receive durvalumab (1500 mg intravenously once every 4 weeks) or placebo with and following chemoradiotherapy, for up to 24 cycles. Chemoradiotherapy included 45 Gy external beam radiotherapy at 5 fractions per week concurrent with intravenous cisplatin (40 mg/m²) or carboplatin (area under the concentration-time curve 2) once weekly for 5 weeks, followed by image-guided brachytherapy (high-dose rate, 27·5-30 Gy or low-dose/pulse-dose rate, 35-40 Gy). Randomisation was stratified by disease stage status (FIGO stage and node status) and geographical region. Chemoradiotherapy quality was continuously reviewed. The primary endpoint was progression-free survival, assessed by the investigator using Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03830866.FINDINGSBetween Feb 15, 2019, and Dec 10, 2020, 770 women were randomly assigned (385 to durvalumab and 385 to placebo; median age 49 years [IQR 41-57]). Median follow-up was 18·5 months (IQR 13·2-21·5) in the durvalumab group and 18·4 months (13·2-23·7) in the placebo group. At data cutoff, median progression-free survival had not been reached (95% CI not reached-not reached) for either group (HR 0·84; 95% CI 0·65-1·08; p=0·17); 12-month progression-free survival was 76·0% (71·3-80·0) with durvalumab and 73·3% (68·4-77·5) with placebo. The most frequently reported grade 3-4 adverse events in both groups were anaemia (76 [20%] of 385 in the durvalumab group vs 56 [15%] of 384 in the placebo group) and decreased white blood cells (39 [10%] vs 49 [13%]). Serious adverse events occurred for 106 (28%) patients who received durvalumab and 89 (23%) patients who received placebo. There were five treatment-related deaths in the durvalumab group (one case each of urinary tract infection, blood loss anaemia, and pulmonary embolism related to chemoradiotherapy only; one case of endocrine disorder related to durvalumab only; and one case of sepsis related to both durvalumab and chemoradiotherapy). There was one treatment-related death in the placebo group (pneumonia related to chemoradiotherapy).INTERPRETATIONDurvalumab concurrent with chemoradiotherapy was well tolerated in participants with locally advanced cervical cancer, however it did not significantly improve progression-free survival in a biomarker unselected, all-comers population. Concurrent durvalumab plus chemoradiotherapy warrants further exploration in patients with high tumoral PD-L1 expression. Rigorous monitoring ensured high chemoradiotherapy compliance with advanced technology and allowed patients to receive optimal care.FUNDINGAstraZeneca.

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