Sumskaya Str, Russian Federation

A Randomised Phase II Study of Roginolisib in Patients With Advanced/Metastatic Uveal Melanoma

A Phase II open-label, randomised, parallel-arm study, which will assess the clinical efficacy of oral roginolisib (IOA 244 [roginolisib hemi-fumarate]) as monotherapy against a control of Investigator´s treatment choice in patients with advanced or metastatic uveal melanoma (UM). This study will enrol approximately 85 male and female patients aged over 18 years with advanced or metastatic UM, who have progressed following at least 1 prior immunotherapy treatment. The disease must be measurable (i.e., at least 1 measurable lesion) as per RECIST v1.1 by Computerised Tomography (CT) scan or Magnetic Resonance Imaging (MRI).

A Clinical Study to Investigate the Efficacy of Tigilanol Tiglate Directly in Head and Neck Cancer

Primary Objective 1. To evaluate tumour ablation following treatment(s) with intratumoural injections of tigilanol tiglate. Secondary Objectives 1. To assess the safety and tolerability of intratumoural injections with tigilanol tiglate. 2. To evaluate disease control by assessing time to local disease recurrence from last treatment. 3. To evaluate the tumour recurrence rate at injected tumour sites. 4. To evaluate survival by assessing Progression Free Survival (PFS). Exploratory Objectives 1. To assess the impact on Quality of Life (QoL). 2. To assess the degree of wound healing after each treatment. 3. To assess the tumour response in injected and non-injected tumours, based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. 4. To assess the tumour response according to intratumoural Response Evaluation Criteria in Solid Tumours (itRECIST). 5. To assess changes in tumour biomarkers. 6. To assess the tumour microenvironment.

Investigation of an Abdominal Compression Device

Stereotactic ablative body radiotherapy (SABR) offers the ability to deliver a high dose of radiotherapy accurately to small tumours. It is an established, effective, non-invasive treatment option for early lung cancers as an alternative to surgery and in the treatment of limited spread of cancer (called oligo-metastatic disease) in the context of clinical trials (CORE, SARON, ABC-07 etc.). In order to deliver a high dose of radiation without damaging the surrounding structures, an accurate map of the tumour and the surrounding organs and their relationship to each other when moving (for e.g. during breathing) is important. This is usually achieved by getting a radiotherapy treatment planning 4 dimensional CT scan (4D-CT). When either the tumour or organ around them (like the lung) are moving excessively it becomes difficult to target the radiation beams and often the only solution is to treat a larger volume which covers the extent of the movement. Treating larger volumes often leads to more toxicity to the surrounding tissues.Therefore managing motion is critical to increasing tumour control probability (TCP) and reducing normal tissue complication probability (NTCP). In this context, the question of reducing the movement caused by breathing, of tumours in the lower lung and upper abdomen (like the liver, adrenals, kidney etc) is an area of intense interest. Various technical and physical methods exist to help improve motion management in patients under going radiotherapy. By limiting the movement, the target volume is smaller and this enables treatment of the tumour to high doses with lesser toxicity as some of the toxicity of radiotherapy is proportionate to the volume treated i.e. lower the volume of treatment lesser the risk of toxicity. Abdominal compression is one such method and is well accepted to be beneficial in reducing tumour motion. However, many of the previous studies require expensive and resource intensive immobilisation devices, costing, in many cases in excess of £10,000. This study will investigate the use of an independent compression device which can be used with any existing immobilisation system and costs in the region of £1,500. If proven to be beneficial this will allow many smaller centres or centres with budget limitations to also achieve the benefits of abdominal compression without extensive resource and cost requirements.

Study to Evaluate CCS1477 (Inobrodib) in Haematological Malignancies

This includes patients with Peripheral T-cell lymphoma.

Magnetic Resonance Imaging for Lung Radiotherapy

Firstly, 3 stage III NSCLC patients receiving radiotherapy will be imaged, each for a single MRI session using TWIST and HASTE sequences. Initial sequence parameters will be those determined during the preceding technical development, but these will be fine-tuned to maximize tumour visualisation as this part of the study progresses, achieving the most practically useful trade-off between image resolution and noise, qualitatively and quantitatively assessed by a radiologist to determine and fine-tune image quality. Then a further 12 patients will be imaged, each for two MRI sessions taking place during the radiotherapy schedule and separated by at least a week. Each MR session will consist of the following sequence: 15 seconds of TWIST, 15 seconds of HASTE, 90 seconds off, 15 seconds of TWIST and 15 seconds of HASTE. For each patient an on-treatment 4D cone-beam CT will also be collected (standard process), alongside the diagnostic quality planning 4DCT. Patient breathing coaching will be consistent between CT and MR, as will patient positioning; that is, patients will be imaged with their arms above their heads. The images will be analyzed to determine - 1. Do extents of tumour movement seen in TWIST 4D-MR images differ from those seen in planning 4D-CT scans, judging the movement extent according to differences in internal target and gross tumour volumes (ITVs and GTVs) defined from the two sets of images, and in the range of motion of the tumour centre of mass? This may well be the case, since the 4D-MR scans catalogue movement over several breathing cycles, whereas 4D-CTs describe a single composite cycle, synthesised from slices collected at various times over multiple cycles. 2. How reproducible is the movement seen at the two MR imaging sessions? Additionally, how reproducible is the movement seen within each MR imaging session? 3. How similar according to volume, Dice similarity index (percentage of overlap) and Haussdorf distance (maximum distance between the contours of two structures) are GTVs outlined on single phases of 4D-CT and TWIST 4D-MR images, after rigidly registering the centres-of-mass of the two GTVs to allow for movement? 4. How consonant are tumour contours defined on single slice HASTE MR images with those defined on a phase of the 4D TWIST images? Answering question 1 will allow us to determine the utility of gauging tumour movement over extended 4D-MR imaging sessions, rather than from 4D-CT sessions which have to be short to avoid excessively irradiating patients. Question 2 will cast further light on the same issue, allowing us to determine the stability over the course of RT schedules of motion assessed over the course of around 1 minute during an individual TWIST scan. Answering question 3 will allow us to understand how fully 4D-MR images can be used within the treatment planning process. If outlined GTVs differ greatly between MRI and CT, then 4D-MRI might only provide more complete movement data; whereas if CT and MRI-based GTVs are similar the 4D-MRI may have more uses in treatment planning, particularly if some tumour regions are more clearly visible on MRI than on CT. Question 4 will allow us to gauge the accuracy and precision of tumour definition on real-time single MRI slices, compared to definition on 4D-MR and 4D-CT. Answering this question is an essential precursor to the development of automatic algorithms

A Phase II Clinical Trial Comparing the Efficacy of RO7198457 Versus Watchful Waiting in Patients with CtDNA-positive, Resected Stage II (high Risk) and Stage III Colorectal Cancer

Patients will receive up to 15 doses of RO7198457 over the course of trial treatment.

Study of RP1 Monotherapy and RP1 in Combination With Nivolumab

RP1 is a genetically modified herpes simplex type 1 virus that is designed to directly destroy tumors and to generate an anti-tumor immune response. This is a Phase 1/2, open label, multicenter, dose escalation and expansion, first-in-human (FIH) clinical study to evaluate the safety and tolerability, biodistribution, shedding, and preliminary efficacy of RP1 alone and in combination with nivolumab in adult subjects with advanced and/or refractory solid tumors. The study will include a dose escalation phase for single agent RP1, an expansion phase with a combination of RP1 and nivolumab and a Phase 2 portion in specified tumor types for the combination therapy.

An Extension and Crossover Vaccination Study on the Immune Response and Safety of a Vaccine Against Respiratory Syncytial Virus Given to Adults 60 Years of Age and Above Who Participated in RSV OA=ADJ-006 Study

A Study to Assess the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Tazemetostat in Combination With Lenalidomide Plus Rituximab Versus Placebo in Combination With Lenalidomide Plus Rituximab in Adult Patients at Least 18 Years of Age With Relapsed/Refractory Follicular Lymphoma.

Stage 1 is a safety run-in phase, was designed to evaluate the safety of the combination of tazemetostat and R2, as well as to establish the RP3D for Stage 2, which is now completed. Stage 2 is an efficacy and safety phase for an assessment of the FL population with the enhancer of zeste homolog 2 (EZH2) gain-of-function (GOF) mutation (EZH2 mutant-type [MT]) and without the EZH2 GOF mutation (EZH2 wild-type [WT]). In Stage 2, EZH2 WT and EZH2 MT patients will be randomly assigned in a 1:1 ratio to tazemetostat + R2 or placebo + R2. There will be 1 futility interim analysis (IA) and 1 efficacy IA for WT population and 1 efficacy IA for MT population. Stage 3 is a long-term follow-up of patients for assessment of response and overall survival. All patients will be followed for survival until 5 years post last patient enrolled in the study.

A Study for Subjects With Prostate Cancer Who Previously Participated in an Enzalutamide Clinical Study

Subjects must continue on the treatment regimen that the subject was receiving in the prior study. Dose changes of any of the prior therapies subjects were receiving on the previous protocol are allowed after medical monitor approval. The day 1 visit for this study should coincide with the last treatment visit for the study the subject will be enrolling from (≤ 7 days post last visit of parent study). The subjects will be followed according to the local institution's standard of care and will be required to return to the institution every 24 weeks (± 7 days) to review adverse events (AEs), collect concomitant medications and confirm that no discontinuation criteria are met. At each visit and at every 12 weeks (IP only visit) subjects are to return all dispensed study drug and to receive more study drug if applicable. All AEs (new and ongoing from the study the subject is enrolling from) and Serious Adverse Events (SAEs) (including death), will be collected from the time the subject signs the consent form until the end of study visit.