Gaithersburg, Maryland

A Real-World Study to Gain Clinical Insights Into Faricimab (FaReal Study)

The Role of HE4 in the Follow-up of Advanced Ovarian, Fallopian Tube and Primary Peritoneal Cancer

Ovarian cancer (OC) is the second most common gynaecologic cancer and the leading cause of death from gynaecologic malignancy among women in industrialized countries. The global incidence in both developed and developing countries can be estimated as 165,000 new cases per year. A heavy difference in prognosis exists between the early-stage disease FIGO I-II (International Federation of Gynaecology and Obstetrics and the advanced stages (FIGO III-IV). Unfortunately, at present, we do not have an effective screening strategy for this malignancy; most (70-80%) of the cases are diagnosed as advanced-stage disease, and this explains the high mortality rate. These aggressive features of the OC encouraged in recent years a big effort in order to find new strategies for early diagnosis of OC. These studies focused dominant on new markers and diagnostic algorithms among new markers. HE4 is one of the most promising. It is a protein initially identified in the epithelium of the distal epididymis and may be involved in sperm maturation. Despite its wide distribution, it is overexpressed only in pathological tissue, and it has demonstrated good sensitivity and specificity in detecting OC, overcoming the traditional role of CA-125. Despite an aggressive upfront treatment strategy (surgery plus chemotherapy), leading to clinical remission in more than 80% of patients, the relapse-free survival varies from 95.8% (for early FIGO stages) to 33.6% (for advanced stages) at 2 years. At present, periodical evaluation of CA-125 combined with physical examination is the recommended strategy for OC follow-up, typically every 3 to 4 months in the first 2 years after primary treatment and then every 6 months until the fifth year. Five years' overall survival rate, however, is 49.7% (ranging from 83%-89% in stage I OC to 18% in stage IV). New markers should be tested in the follow-up of patients with OC to improve the surveillance program performance: the challenge is to try to anticipate the diagnosis of OC recurrence and to translate this early diagnosis of relapse in a survival improvement. Few studies only are available to date about HE4 use in follow up of ovarian cancer. All of these studies analyzed a small number of women (8-73). HE4 was shown as an earlier indicator of recurrence of OC with respect to CA-125, with a lead-time of 5 to 8 months. Only 1 prospective controlled study has been published. In this study the sensitivity and specificity of HE4, alone or in association with other markers (CA-125, CA-72-4), seems to be higher in the diagnosis of the OC relapse with respect to CA-125 alone. The other side of the question is whether the patient is advantaged by an earlier detection of the recurrent disease, in terms of overall survival, disease-free survival, and quality of life. Early detection and treatment of cancer in general or its recurrence are usually associated with better outcomes for patient, this being the rationale behind screening programs and follow-up strategies. In OC follow-up, periodical CA-125 evaluation can detect recurrence of cancer about 5 months before clinical signs or symptoms. At the same time, we have to remind, that treatments of relapsing OC are rarely curative and have heavy adverse effects, and elevation of CA-125 is often cause of anxiety in patients undergoing follow-up. The main study, that tried to clarify the role of CA-125 in OC follow-up was MRC OV05/EORTC (European Organisation for Research and Treatment of Cancer) 55955 trial a randomized study comparing early versus delayed treatment in women with relapsed OC. Patients in the delayed treatment group were treated only at clinical or symptomatic relapse. Women assigned to early treatment started chemotherapy 4.8 months earlier than those allocated to the delayed treatment. With a median follow-up of 56.9 months, there was no evidence of a difference in overall survival between the 2 groups. In particular, the results provided no evidence of an improved overall survival or a better quality of life in the early treatment group. The authors' explanation for these findings was that the lead-time between CA-125 rise and the clinical recurrence could be too short for chemotherapy to give a beneficial effect. At present, periodical evaluation of CA-125 combined with physical examination is the recommended strategy for OC follow-up, typically every 3 to 4 months in the first 2 years after primary treatment and then every 6 months until the fifth year. Five years' overall survival rate, however, is 49.7% (ranging from 83%-89% in stage I OC to 18% in stage IV).

Study to Continue Treatment With Darolutamide in Patients Who Have Been Participating in Previous Darolutamide Studies Supported by Bayer

A Study of Milvexian in Participants After an Acute Ischemic Stroke or High-Risk Transient Ischemic Attack- LIBREXIA-STROKE

An Open-label Study Comparing Lutetium (177Lu) Vipivotide Tetraxetan Versus Observation in PSMA Positive OMPC.

All participants will be assessed for eligibility and will undergo baseline disease assessments including a mandatory gallium (68Ga) gozetotide (also known as [68Ga]Ga-PSMA-11) or piflufolastat (18F) ( also known as[18F]DCFPyL) PET/CT scan and conventional imaging (i.e., CT/MRI and bone scans). Piflufolastat (18F) PET/CT scan will be performed in countries where it is approved. Stereotactic Body Radiation Therapy (SBRT) will be administered to all metastatic Prostate Cancer (PC) lesions after randomization and before the start of treatment with AAA617 or observation. - The duration of SBRT procedures is approximately 3 weeks. - For participants randomized to the investigational arm (AAA617), the treatment duration will be up to 4 cycles of AAA617. For participants randomized to the control arm (observation) the treatment duration will end at the last fraction of SBRT administration. - The visit frequency will be every week 1 and 3 of each of the 4 cycles and every 16 weeks thereafter (for both arms) until first event of disease progression (RECIST 1.1) - The study duration is approximately 6.5 years.

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.

A Study to Learn How PF-06821497 (Mevrometostat) Works in Men With Metastatic Castration-resistant Prostate Cancer.

This is a global, multicenter, randomized Phase 3 study evaluating PF-06821497 (mevrometostat) in combination with enzalutamide versus placebo in combination with enzalutamide in participants with mCRPC where no systemic anti-cancer treatments have been initiated after documentation of mCRPC with the exception of ADT (androgen deprivation therapy) and first-generation anti-androgen agents. Prior treatment with any of the ARSi's enzalutamide, darolutamide, apalutamide, or abiraterone acetate, is not permitted in any setting. Chemotherapy is permitted in the castrate sensitive setting. This study consists of a Screening Phase, Randomization, Treatment Phase, Safety Follow-up, and Long-Term Follow-up. Participants will be randomized on a 1:1 basis to receive (Arm A) PF-06821497 in combination with enzalutamide, or (Arm B) placebo in combination with enzalutamide.