Tislelizumab in Combination With Sitravatinib for Recurrent/Metastatic Cervical Cancer After Platinum-Based Chemotherapy (ITTACC)

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 AST and ALT ≤ 3x ULN (or ≤ 5.0x ULN, if liver metastases) ALP ≤ 2.5x ULN (or ≤ 5.0x ULN, if liver or bone metastases) Serum creatinine ≤ 1.5x ULN or estimated creatinine clearance > 45mL/min using the Cockcroft-Gault equation Patients must meet at least one of the following criteria regarding prior bevacizumab therapy: Received prior bevacizumab-containing therapy, which was discontinued due to progression of disease Received prior bevacizumab-containing therapy, which was discontinued due to toxicity Was deemed unsuitable for prior bevacizumab therapy for one of the following reasons: (i) unacceptable risk of fistula formation, (ii) poorly controlled hypertension, (iii) "low risk" disease according to the Moore Criteria Refused prior bevacizumab therapy Patients must meet at least one of the following criteria regarding prior paclitaxel therapy: Received prior paclitaxel-containing therapy, which was discontinued due to progression of disease Received prior paclitaxel-containing therapy, which was discontinued due to toxicity Was deemed unsuitable for prior paclitaxel therapy for one of the following reasons: Significant neuropathy Allergy to paclitaxel or its components Refused prior paclitaxel therapy 1 prior line of combination which include an anti-PD-1/ anti-PD-L1 inhibitor Previous progression after cisplatin or carboplatin-based combinations Anticipated life expectancy > 12 weeks Willing and able to comply with clinic visits and study-related procedures Availability of archival tumour sample from either the primary or metastatic tumour. If no archival tumour is available, a fresh tissue biopsy to be performed if feasible and safe to do so. Where tumour tissue is not available, this will not preclude trial participation 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 Any ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months prior to registration QTc ≥ 470msec in females and ≥ 450msec in males (based on average of screening triplicates) Cardiac LVEF ≤ 50% or lower limit of normal as assessed by echocardiography or MUGA Patients with inadequately controlled hypertension (defined as systolic blood pressure > 150mmHg and/or diastolic blood pressure > 100mmHg, that is persistent) Any history of cerebrovascular accident ≤ 6 months prior to registration Significant bleeding and thrombotic risks: Patients with bleeding or thrombotic disorders or who use anticoagulants such as warfarin or similar agents requiring therapeutic INR monitoring Patients with signs or history of significant bleeding, within 4 weeks prior to registration, patients with any bleeding events ≥ CTCAE Grade 3, unhealed wounds, ulcers, or fractures Patients with arterial thrombotic event that occurred within 6 months prior to registration, such as cerebrovascular accident (including temporary ischemic attack) Venous thrombotic events such as deep vein thrombosis and pulmonary embolism that causes haemodynamic compromise or venous thrombotic events within 4 weeks of diagnosis (treated asymptomatic patients > 4 weeks after diagnosis permitted at Investigators' discretion) Immunosuppressive corticosteroid doses (> 10mg prednisone daily or equivalent) within 4 weeks prior to registration Active bacterial, viral, fungal or mycobacterial infection requiring therapy, including known infection with HIV, or active infection with HBV or HCV History of pneumonitis within the last 5 years Any anticancer treatment (chemotherapy, targeted systemic therapy, photodynamic therapy), investigational, or standard of care, within 30 days prior to registration or planned to occur during the study period (patients receiving bisphosphonates or denosumab are not excluded) History of documented allergic reactions or acute hypersensitivity reactions attributed to antibody treatments Concurrent malignancy other than cervical cancer and/or history of malignancy other than cervical cancer within 3 years prior to registration, except for tumours with negligible risk of metastasis or death, such as adequately treated cutaneous squamous cell carcinoma or basal cell carcinoma of the skin or ductal carcinoma in situ of the breast. Patients with hematologic malignancies (e.g., CLL) are excluded Any acute or chronic psychiatric problems that, in the opinion of the Investigator, make the patient ineligible for participation Patients with a history of solid organ transplant (patients with prior corneal transplant(s) may be allowed to enrol after discussion with and approval from the CPI) Any medical co-morbidity, physical examination finding, or metabolic dysfunction, or clinical laboratory abnormality that, in the opinion of the Investigator, renders the patient unsuitable for participation due to excessive safety risks and/or potential to affect interpretation of results of the study Pregnant or breastfeeding persons People of Childbearing Potential who are unwilling to practice highly effective contraception prior to the initial study drug treatment, during the study, and for at least 6 months after the last dose. Prior treatment with idelalisib Prior treatment with live vaccines within 30 days prior to registration. Patients must not be treated with live vaccines during the study and up to 5 half-lives following the last dose of study drug Patients with prior treatment on any clinical trial within 30 days prior to registration. Non-interventional and observational trials are acceptable