
A Study of the Safety, Tolerability and Effectiveness of EZM0414 Investigative Product in Participants...
Multiple MyelomaRefractory3 moreThis study will include participants with relapsed/refractory (R/R) Multiple Myeloma (MM). MM is a type of cancer of the blood. This study will also include participants with relapsed/refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL). DLBCL is also a type of cancer of the blood. They are referred to as 'relapsed' when the disease has come back after treatment and 'refractory' when treatment no longer works. The study has 2 main parts, called phase 1 and phase 1b. The main objective of both parts will be to evaluate the safety and tolerability of the study drug, called EZM0414. The main objective of phase 1b will also be to determine the effectiveness of EZM0414. During phase 1 six dose levels will be tested to obtain the most tolerated dose. Participants will receive study drug at the assigned dose level every 28 days. During phase 1b participants will receive study drug at the maximum tolerated dose in 28-day cycles.

Efficacy and Safety of TPIAT for Resectable Adenocarcinoma of the Pancreas Region at High Risk of...
Adenocarcinoma of the PancreasAdenocarcinoma of the Duodenum1 moreCurative management of locally resectable invasive adenocarcinomas located in the cephalic region of the pancreas (pancreas, duodenum and ampulla of Vater) requires a pancreaticoduodenectomy followed by adjuvant chemotherapy. Pancreaticoduodenectomy is a major surgery that often leads to major complications including approximately 20% of relevant clinical postoperative pancreatic fistula. Postoperative complications following pancreaticoduodenectomy can lead to early discontinuation of the complete oncologic strategy, i.e., chemotherapy for malignancy is performed in only about a third of patients who experienced a grade C fistula. A total pancreatectomy rather than a pancreaticoduodenectomy is an alternative procedure that involves the complete and definitive resection of all pancreatic tissue, eliminating any risk of postoperative pancreatic fistula but is associated with unavoidable endocrine insufficiency and potentially severe metabolic complications, such as "brittle diabetes". Total Pancreatectomy following by intraportal Islet AutoTransplantation (TPIAT) can prevent "brittle diabetes" and improve the quality of life. The endocrine islets can be isolated from the pancreatic surgical specimen with standardized procedures and transplanted in the liver through intraportal infusion, in absence of immunosuppression and allow adequate control of glucose metabolism with a reduced need for exogenous insulin and an effective graft function in 70% of cases at 3 years Thereby, the investigators hypothesize that total pancreatectomy with intraportal Islet autotransplantation rather than classical pancreaticuduodenectomy, in patients with high-risk of postoperative fistula will increase the rate of complete access to adjuvant chemotherapy, while maintaining an adequate metabolic control.

Orelabrutinib, Rituximab and Combination Chemotherapy in Newly-diagnosed Aggressive B-cell Non-Hodgkin...
High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 RearrangementsHigh Grade B-Cell Lymphoma4 moreB-cell non-Hodgkin's lymphoma (B-NHL) is the most common type of NHL. Although novel immunotherapies represented by anti-CD20 monoclonal antibodies and CAR-T cell therapies have significantly improved the prognosis of B-NHL patients, there are still nearly one-third of patients who are resistant to initial treatment or relapse after remission. R-CHOP combined with novel drugs was expected to improve the prognosis. Therefore, this study aimed to investigate the potential of Orelabrutinib combined with Rituximab and chemotherapy.

Adaptive ChemoTherapy for Ovarian Cancer in Patients With Replased Platinum-sensitive High Grade...
Ovarian CancerRelapsed Ovarian Cancer5 moreACTOv will compare standard 3-weekly carboplatin (AUC5), to carboplatin delivered according to an AT regimen. The AT regimen will modify carboplatin dose according to changes in the clinical-standard serum biomarker CA125 as a proxy measure of total tumour burden and an individual patient's response to the most recent chemotherapy treatment. AT could prolong sensitivity to carboplatin and extend tumour control, while simultaneously reducing chemotherapy dose and drug-induced toxicity. Carboplatin is a low cost and low toxicity drug that has an enduring and central role in ovarian cancer treatment.

Safety and Toxicity Study of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle...
Non-muscle Invasive Bladder CancerThis study is an open-label dose escalation study (Phase 1a) to investigate the safety and toxicity of intravesical treatment of high-grade NMIBC (HGTa or CIS, including CIS with concomitant Ta) after transurethral resection of bladder tumor (TURBT) and/or biopsy using TARA-002 in adults unable to obtain intravesical Bacillus Calmette-Guérin (BCG), adults who have received at least one dose of intravesical BCG or adults who have received at least one dose of intravesical chemotherapy. Dosing will start in subjects with HGTa or CIS (including CIS with concomitant Ta), and all subjects will receive 6 weeks of treatment at a fixed volume with varying dose levels.

Thymosin-alpha 1 for Adjuvant Treatment After Radical Resection of High-risk Stage II and III Colorectal...
Stage II Colorectal CancerStage III Colorectal CancerFor high-risk stage II and stage III colorectal cancer, even after radical resection and postoperative adjuvant chemo/radiotherapy, 30-40% of patients will still have recurrence and metastasis. Thymosin-alpha 1 is believed to improve immunity and may help promote tumor immunity to reduce the incidence of recurrence and metastasis. This study hopes to verify the effecacy and safety of thymosin-alpha 1 for adjuvant treatment of high-risk stage II and stage III colorectal cancer after radical resection.

A Phase 1b/2 Clinical Study to Evaluate the Safety and Tolerability and Efficacy of AZD4547
Urothelial CarcinomaPhase 1b clinical study to evaluate the PK of oral AZD4547 in Chinese patients and RP2D. Phase 2 study to evaluate the efficacy of AZD4547 in urothelial carcinoma patients with FGFR2/3 gene alterations.

A Study to Investigate Safety and Tolerability of TransCon IL-2 β/γ Alone or in Combination With...
Advanced Solid TumorLocally Advanced Solid Tumor6 moreTransCon IL-2 β/γ is an investigational drug being developed for treatment of locally advanced or metastatic solid tumors. This is a first-in-human, open-label, Phase 1/2, dose escalation and dose expansion study of TransCon IL-2 β/γ as monotherapy or in combination therapy in adult participants with advanced or metastatic solid tumors. Given the unique PK profile enabled by the TransCon technology, TransCon IL-2 β/γ presents the opportunity to enhance the therapeutic index of current IL-2 therapy.

Study of αPD1-MSLN-CAR T Cells to Evaluate the Safety, Tolerability, and Effectiveness for Patients...
Colorectal CancerThis is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of autologous mesothelin (MSLN)-targeted chimeric antigen receptor (MSLN-CAR) T cells secreting PD-1 nanobodies (αPD1-MSLN-CAR T cells) in patients with solid tumors.

HIFU Ablation of Soft Tissue Sarcoma
Soft Tissue SarcomaDesmoid; AbdominalAround 3,300 people are diagnosed with soft tissue sarcoma (STS) each year in the UK, and a significant proportion of STS diagnoses are in people aged under 30 years. STS can arise from various tissue types and is comprised of over 50 tumour types. Although STS is treated with a combination of surgery, radiotherapy and chemotherapy, the prognosis is relatively poor with a five-year survival rate of 54%. There is an unmet need for further treatment modalities in STS. High intensity focused ultrasound (HIFU) is a non-invasive way of treating cancers with minimal side effects, low complication rate and quick recovery. Ultrasound waves are used to destroy tumour cells and improvements in technology and experience are enabling complete destruction of tumour. HIFU also releases tumour antigens, increasing the immune response against cancer. HIFU has received FDA approvals for several indications, including bone metastases and we are using a CE-approved HIFU device in Oxford (UKCA-approvals anticipated for 2023). There have been some publications from China showing promise in STS, however this technology needs further evaluation within the UK's healthcare setting. This study will recruit patients with both resectable and unresectable STS, in addition to unresectable small symptomatic desmoid tumours. 12-16 patients, and a minimum of 10 patients with malignant STS, will be treated over a maximum recruitment period of three years. HIFU treatment will be carried out as a day case procedure, and patients will be expected to be discharged home the same day. The study is designed to generate evidence regarding safety and feasibility of HIFU for ablation of STS and intra-abdominal desmoids. In addition, the study is anticipated to provide information about the efficacy of HIFU against these tumour types which can help in the design of later phase studies. Short-term outcomes include feasibility, safety and the completeness of destruction of the tumour. Long-term outcomes include one-year survival, local recurrence and quality of life metrics (including pain scores). The study will also look at immunological response following ablation of STS using both blood and tumour samples pre- and post-HIFU ablation.