A Phase II Trial of Tislelizumab in Combination With Sitravatinib for Recurrent/Metastatic Cervical Cancer After Platinum-Based Chemotherapy

Australia New Zealand Gynaecological Oncology Group0 sitesJune 2023

ConditionsMetastatic Cervical Cancer

InterventionsTislelizumab Sitravatinib

DrugsTislelizumab Sitravatinib

Overview

Phase: Phase 2
Intervention: Tislelizumab
Conditions: Metastatic Cervical Cancer
Sponsor: Australia New Zealand Gynaecological Oncology Group
Primary Endpoint: Overall Response Rate (ORR)
Status: Withdrawn
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

The goal of this clinical trial is to learn about the effect of the combination treatment of sitravatinib with tislelizumab in patients with Recurrent/Metastatic Cervical Cancer after Platinum-Based Chemotherapy.

The main question it aims to answer is the percentage of people in the study who have a partial or complete response to the treatment.

Participants will receive treatment under the care of their treating physician and will be reviewed regularly.

Detailed Description

Monoclonal antibodies that target either PD-1, PD-L1, or the other checkpoint inhibitors can block binding and boost the immune response against cancer cells. However, many early-phase studies with single immune checkpoint inhibitors did not show enough power to achieve a promising clinical response, and several trials are evaluating different strategies to overcome immune tolerance via combination therapies. Combining an immunotherapeutic PD-1 checkpoint inhibitor with an agent that has both immune modulatory and antitumor properties could enhance the antitumor efficacy observed with either agent alone. Sitravatinib is a spectrum selective RTK inhibitor that inhibits several closely related RTKs, including the TAM family (Tyro3/Axl/MER), VEGFR2, KIT, and MET. Tislelizumab is a humanised IgG4-variant monoclonal antibody against PD-1. In addition to the antiangiogenesis activity of sitravatinib, sitravatinib in combination with tislelizumab may elicit greater anti-tumour activity, as sitravatinib is predicted to enhance several steps in the cancer immunity cycle that may augment the efficacy of tislelizumab. In summary, sitravatinib inhibits key molecular and cellular pathways strongly implicated in carcinogenesis and drug resistance and represents a reasonable strategy to enhance anti-tumour immunity when combined with tislelizumab. The ITTACc study aims to assess the overall response rate of the combination of tislelizumab with sitravatinib along with other key outcomes detailed below.

Registry

clinicaltrials.gov

Start Date

June 2023

End Date

June 28, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Australia New Zealand Gynaecological Oncology Group

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patient has provided written informed consent
•Patient must be ≥ 18 years of age at screening
•Recurrent, persistent, and/or metastatic cervical cancer with squamous cell histology, adeno-squamous carcinoma, and adenocarcinoma for which there is not a curative-intent option (surgery or radiation therapy with or without chemotherapy)
•Measurable disease, as defined by RECIST 1.1
•ECOG performance status ≤ 2
•Adequate bone marrow, hepatic and renal function documented within 10 days prior to registration, defined as:
•Haemoglobin ≥ 90g/L
•ANC ≥ 1.5 x 109/L
•Platelets ≥ 75 x 109/L
•Total bilirubin ≤ 1.5x ULN if liver metastases ≤ 3x ULN. Patients with Gilbert's syndrome, and total bilirubin up to 3x ULN may be eligible after communication with and approval from the CPI

Exclusion Criteria

•Ongoing or recent (within 5 years prior to registration) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest higher risk for severe irAEs. The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that required only hormone replacement, or psoriasis that does not require systemic treatment
•Prior treatment with other systemic immune-modulating agents that was (a) within fewer than 28 days prior to registration, or (b) associated with irAEs of any grade within 90 days prior to registration, or (c) associated with toxicity that resulted in discontinuation of the immune-modulating agent.
•Known history of brain metastasis(es) that may be considered active (screening imaging of brain is not required unless there is clinical suspicion of brain metastases). Patients with previously treated brain metastases may participate provided that the lesions are stable (without evidence of progression for at least 6 weeks on imaging obtained during the screening period), there is no evidence of new or enlarging brain metastases, and the patient does not require any immunosuppressive doses of systemic corticosteroids for management of brain metastases within 4 weeks prior to registration
•Variant histology's such as high-grade neuroendocrine carcinoma, small cell carcinoma, mucinous carcinoma, sarcomatous tumours or mixed histology's containing these components
•Patients with tumour shown by imaging to be located around important vascular structures or if the Investigator determines that the tumour is likely to invade important blood vessels and may cause fatal bleeding (i.e., radiological evidence of tumours invading or abutting major blood vessels)
•Any of the following cardiovascular risk factors:
•Cardiac chest pain, defined as moderate pain that limits instrumental ADL, ≤ 28 days prior to registration
•Symptomatic pulmonary embolism ≤ 28 days prior to registration
•Any history of acute myocardial infarction ≤ 6 months prior to registration
•Any history of heart failure meeting NYHA Classification III or IV ≤ 6 months prior registration