Two Phase III trials are currently being conducted by the Gynaeoncology Group Singapore (GOGS) at the National Cancer Centre Singapore (NCCS), KK Women’s and Children Hospital (KKH), and the National University Cancer Institute, Singapore (NCIS) for the treatment of newly diagnosed cervical cancer.

In the first study, the GOGS investigators at NCCS, KKH and NCIS are using Z–100 – a compound that activates the immune system to target cancer – in combination with conventional chemotherapy and radiotherapy (i.e., chemoradiotherapy).

The immunotherapy vaccine Z–100 has been previously evaluated in two earlier studies in Japan (PIII–1 study, PIII–2 study) involving more than 300 patients, with promising results and low toxicity. A global multicentre phase III study looking at the role of Z–100 at 0.2 ug vs placebo for patients with newly diagnosed stage IIIB cervical cancer was initiated, and in Singapore this study is being undertaken by the Gynaeoncology Group Singapore (GOGS) and currently recruiting patients at NCCS, KKH and NCIS.

Adj Assoc Prof John Chia, Co–Principal Investigator of this study and Senior Consultant Medical Oncologist, NCCS explained, “Current evidence seems to indicate that cervical cancer is amenable to immune attack, and there is currently intense global interest in using a variety of immune activating strategies to treat this disease.”

“Clinical trials in US, Europe and Asia are exploring various approaches using immunotherapy for cervical cancer – including immune checkpoint antibodies, dendritic cell therapy, natural killer cell therapy, HPV peptides vaccines, and various immune activating agents,” Adj Assoc Prof Chia said.

In the study, patients with FIGO stage IIIB cervical cancer will be randomised to receive either a subcutaneous (under the skin) injection of Z–100 or placebo twice a week at intervals of three to four days during their chemotherapy and radiotherapy. Once the chemoradiation is completed, patients will then receive the Z–100 or placebo injection once in two weeks for up to five years.

Asst Prof David Tan, Co–Principal Investigator of this study and Consultant, Department of Haematology–Oncology, at NCIS said, "Locally advanced cervical cancer is a very challenging disease with a high risk of disease relapse despite chemotherapy and radiation, so it is crucial that we identify better treatment options to improve outcomes for our patients with this condition.”

Asst Prof Tan added: “Z–100 is a very interesting drug that has been shown to have immunomodulatory and anti–cancer properties (i.e. may enhance the immune system to fight cancer) and previous studies suggest patients with stage IIIB locally advanced cervical cancer may benefit in terms of treatment response and survival when Z–100 is combined with radiation.”

Assistant Professor Lim Sheow Lei, Co–Principal Investigator of this study and Senior Consultant, Department of Gynaecological Oncology, KKH, said, “Z–100 belongs to a new and exciting class of anti–cancer treatment called immunotherapy, which harnesses patients’ own immune system to fight cancer. Immunotherapy has already demonstrated promising results in the treatment of certain types of cancer, such as skin and lung cancers.”

In the second study, a global multicentre phase III study known as the OUTBACK trial, GOGS investigators at NCIS are looking at whether additional chemotherapy with carboplatin and paclitaxel after completion of the standard treatment with chemoradiotherapy, can improve survival outcomes for patients with newly diagnosed stage IB1 & positive nodes, IB2, II, IIIB or IVA cervical cancer.