Guildford

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab as a 1L treatment for patients with mNSCLC whose tumors express PD-L1.

This is a multicenter, open-label, non-comparative, phase II, biomarker-driven adjuvant treatment Study involving the periodic collection and analysis of blood samples from patients with HR-positive/HER2- negative early-stage BC at higher risk of relapse, who have undergone surgery, have received radiotherapy if indicated as per local guidelines, with no evidence of locoregional, contralateral, or distant disease. Patients must be on adjuvant treatment with ET for at least two years and no more than seven years at the time of Study enrolment with an additional three years of ET planned. At least 6 months prior to enrolment on the same ET treatment (AI or tamoxifen). LHRH is mandatory for men and premenopausal women receiving AI, as well as for premenopausal women treated with tamoxifen, except in cases of bilateral oophorectomy). The trial design entails an initial pre-screening phase, a molecular follow-up phase (ctDNA surveillance phase), and an interventional therapeutic phase (treatment phase). After informed consent is obtained, 976 eligible patients will enter a ctDNA surveillance in which primary tumor tissue and matched normal blood will be collected from each patient to obtain a patient-specific somatic mutations panel (tumor signature). Note: Additional patients may enter the ctDNA surveillance phase if needed, for example if additional arms are opened. Then, blood will be collected, processed, and analyzed to detect the presence or absence of ctDNA at predefined time points for longitudinal surveillance. ctDNA analysis will occur every three months from Study inclusion during the first year and every six months thereafter until positive result or end of accrual. At the event of ctDNA positivity, patients will be screened to enter the treatment phase of the Study. Upon confirmed eligibility, a total of 40 patients will be allocated in one of the following trial's arms adopting a sequential recruitment strategy. Arm A: Experimental Arm with standard treatment followed by change in treatment (N=10) Arm B: Experimental Arm with giredestrant (N=10) Arm C: Experimental Arm with giredestrant + abemaciclib (N=10) Arm D: Experimental Arm with giredestrant + inavolisib (N=10) Note I: In addition to the treatments described on each of the treatment arms, LHRH agonist will be administered to male participants and pre-menopausal/perimenopausal participants according to local prescribing information. The patient should be supplied with the previous LHRH they were taking. Note II: During the length of the study, additional treatment arms may open to stay up to date with the most recent advances in oncology, and to be able to provide the best treatment options to patients in this study. Because of that, the N of patients screened to enter the treatment phase may increase. Note III: For patients eligible to receive inavolisib with a creatinine clearance between 30 and \<60 mL/min, as estimated by the 2021 CKD-EPI creatinine equation (National Kidney Foundation, 2021), the starting dose is 6 mg orally once daily (PO QD) on Days 1-28 of each 28-day cycle. In the meanwhile, serial assessment of ctDNA will be continuously performed every three months during the first year and every six months thereafter until EoS to correlate any ctDNA variations with response. Patients discontinuing the Study treatment period will enter a post-treatment follow-up period during which survival and new anti-cancer therapy information will be collected every three months (±14 days) from the last dose of Study treatment up to the EoS. Telephone contact is acceptable (in some countries medical information can only be shared directly in person with the patient). Arm extensions After initiation of Study treatments, data obtained from serial assessment of ctDNA will also be used to confirm feasibility of eventual arms extensions, with maximum two arms that could be expanded (10 additional patients will be enrolled in each of the selected arms). The expansion will be approved when the arm complies with the following criteria: * If at three months, a 90% ctDNA decrease is observed in at least 30% patients and if after three additional months, a 90% ctDNA decrease is maintained in at least 20% patients In this case, 10 additional patients will be enrolled in the specific experimental arms that meet these requirements (N=20). * If all three experimental arms fulfill the criteria, the two arms with the highest proportion of patients with the highest proportion of 90% decrease will be the ones expanded. * If cohorts remain too similar (no clear "winners"), the decision will be taken by the Steering Committee based on the duration of the response and the safety and toxicity of each specific treatment. * If none of the arms fulfill the specific expansion criteria, the Steering Committee will evaluate the data further and may nominate the two arms with the strongest signal of ctDNA decreases for further expansion. If the strategy of ctDNA monitoring enables physicians to identify patients at high risk of relapse and assess whether treatment at molecular relapse can improve outcome, new cohorts may be added to the study

Immunotherapy with pembrolizumab targeting the T cell inhibitory PD-1 receptor has significantly improved outcomes in advanced non-small cell lung cancer (NSCLC). Approximately 3600 new patients are treated in the 1st line setting per year in England alone and up to 25% remain on 6 weekly pembrolizumab for 2 years. However, pharmacological and clinical trial data suggest current frequent dosing for 2 years result in overtreatment. Indeed, pembrolizumab remains bound to its target receptor for up to 100 days following a single dose and studies in multiple tumour types have found no relationship between dose and patient outcome. Moreover, anti-PD1 treated patients who respond but discontinue therapy either as planned after 2 years, or earlier because of toxicity, can either remain in remission and/or be sensitive to re-challenge with pembrolizumab. REFINE-lung will test whether reduced pembrolizumab dose frequency (9, 12, 15, 18 weeks) after 6 months of standard treatment is safe and effective. This UK study represents a unique opportunity to determine whether pembrolizumab dose frequency can be safely reduced in NSCLC, resulting in significant cost benefits to the NHS and globally, in addition to enhanced patient QoL associated with fewer hospital attendances and reduced toxicity.

This is a trial to evaluate the efficacy, safety, and tolerability of adagrasib plus pembrolizumab plus platinum-doublet chemotherapy versus placebo plus pembrolizumab plus platinum-doublet chemotherapy in participants with previously untreated, locally advanced or metastatic NSCLC with KRAS G12C mutation

The purpose of this study is to determine safety and preliminary efficacy of amivantamab monotherapy, amivantamab in addition to pembrolizumab, amivantamab in addition to paclitaxel and amivantamab in addition to pembrolizumab and carboplatin in participants with recurrent/metastatic head and neck cancer. The study will also confirm the recommended Phase 2 combination dose (RP2CD) for amivantamab in addition to paclitaxel. The safety and preliminary efficacy of amivantamab in addition to pembrolizumab will also be determined in perioperative (before and after surgery) setting in participants with resectable locally advanced head and neck squamous cell carcinoma (HNSCC).

The purpose of this study is to compare anti-tumor activity of amivantamab in addition to pembrolizumab and carboplatin versus pembrolizumab, 5-fluorouracil (FU), and platinum therapy (carboplatin or cisplatin) in participants with refractory/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). HNSCC is a type of cancer that develops in the head and neck regions, including the outer tissue layer of the mouth and throat. This study will focus on participants with HNSCC who are treatment-naive (have not received prior treatment) in the R/M setting.

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard endocrine therapy in patients with ER+/HER2 - early breast cancer who completed definitive locoregional therapy (with or without chemotherapy) and standard adjuvant endocrine therapy (ET) for at least 2 years and up to 5 years. The planned duration of treatment in either arm of the study is 60 months. The eligible patients must have intermediate or high risk of recurrence, as defined by specified clinical and biologic criteria. Prior use of CDK4/6 inhibitors is permitted. The primary endpoint of the study is Invasive breast cancer-free survival (IBCFS) and main secondary endpoints include Invasive disease-free survival (IDFS), Distant relapse-free survival (DRFS), Overall survival (OS), Safety and Clinical Outcome Assessments (COAs). Patients will be followed for 10 years from randomization of the last patient.

TRAILBLAZER-ALZ 5 is a Phase 3, double-blind, placebo-controlled study to evaluate the safety and efficacy of donanemab in participants with early symptomatic AD (prodromal AD and mild dementia due to AD) and the presence of AD pathology.

Approximately, 700 adult participants with localised/locally advanced prostate cancer will be randomized in a 1:1 ratio to receive saruparib or placebo with ADT (+ abiraterone) in one of the following two cohorts: Cohort A: 400 adult participants with newly diagnosed high-risk and very high-risk (localised/locally advanced) prostate cancer who have received primary RT and are receiving continuous ADT, and participants with high-risk biochemical recurrence (BCR) \[including prostate-specific antigen (PSA) persistence\] following a radical prostatectomy who have received salvage RT are receiving continuous ADT. Cohort B: 300 adult participants with newly diagnosed very high-risk (locally advanced) prostate cancer who have received primary RT and who are receiving continuous ADT and abiraterone. All participants will be followed for survival until the end of the study. Independent data monitoring committee (DMC) composed of experts will be convened to confirm the safety and efficacy of Saruparib + ADT (+ abiraterone).

One of the standard treatments for women with breast cancer is hormone therapy, but this treatment can cause hot flashes. Hormone replacement therapy, or HRT, is most often prescribed for hot flashes for women in menopause but cannot be given to women on hormone therapy for breast cancer. Fezolinetant, an alternative to HRT, treats hot flashes for women in menopause. As hot flashes happen in the same way for women on hormone therapy for breast cancer, fezolinetant could help these women. In this study, women on hormone therapy for breast cancer who have moderate to severe hot flashes will take part. They will either take fezolinetant or a placebo to treat their hot flashes. The placebo looks like fezolinetant but doesn't have any medicine in it. The main aim of this study is to confirm if women who take fezolinetant have fewer hot flashes that are less severe compared to women who take the placebo. Women 18 years or older seeking treatment for hot flashes. They can take part in the study if they have an average of 7 or more moderate to severe hot flashes each day. They are having hormone therapy for breast cancer from stage 0 (cancer cells that have not spread to nearby tissue) up to stage 3+ (the cancer has spread from the breast to the lymph nodes near the breast or the chest wall). The women will be assigned 1 of 2 study treatments (fezolinetant or placebo) by chance alone. Treatment will be double-blinded. That means that the women in the study and the study doctors will not know who takes which of the study treatments (fezolinetant or placebo). Women who take part in the study will take 1 tablet every day for 52 weeks (1 year). Each woman will be given an electronic handheld device with an app to track their hot flashes on a daily basis. Some women may be able to use the app on their own smartphone. They will also use another device to answer questions about how hot flashes affect their daily life. During the study, the women will visit their study clinic about every 4 weeks for a health check. The last clinic visit will be 3 weeks after the women take their last tablet of study treatment (fezolinetant or placebo). After this visit the women will be called twice to check their health. The women will be in the study for about 2 years.