A randomized phase II trial of adjuvant pembrolizumab versus observation following curative resection for stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm: Big Ten Cancer Research Consortium BTCRC-LUN18-153.

TPS8583 Background: There are approximately 35,000 cases of stage I lung cancer in the United States each year. While these patients have better 5-year overall survival (OS) rates than their counterparts with locally advanced and metastatic disease, there is still considerable room for improvement. Based on a recent publication validating the 8th edition of the TNM classification, the 5-year OS for node-negative pathologically-staged NSCLC between 1-4cm ranges from 73-86%, and recurrence rates for resected stage I NSCLC can range from 18-38%. Previous studies looking at adjuvant chemotherapy in this setting have shown no benefit for stage IA tumors, and the current standard of care is observation alone. Checkpoint blockade with PD-1/PD-L1 inhibitors has shown considerable activity in NSCLC including in metastatic disease, as consolidation in stage III disease after chemoradiation, and in studies evaluating neoadjuvant immunotherapy. Given this activity and their favorable safety profile, we designed a study of adjuvant PD-1 inhibition following resection in stage I NSCLC. Methods: This study is a randomized phase II multicenter trial of adjuvant Pembrolizumab versus observation alone following complete resection of stage I NSCLC with tumors between 1-4cm. The trial will enroll 368 patients randomized 1:1 to either Pembrolizumab 400mg IV every 6 weeks for up to 9 cycles or observation alone with scheduled CT scans and routine clinical follow-up. Stratification factors include PD-L1 ≥50% vs. < 50% and tumor size of 1-2cm vs. > 2-4cm. The lead site is Indiana University, and the trial will be conducted through the Big Ten Cancer Research Consortium. The primary endpoint is disease free survival (DFS), and secondary endpoints include OS, DFS at 1-, 2-, and 3-year time points, and toxicity. The trial opened to accrual at the lead site in May 2020, and there are currently 6 patients enrolled. Clinical trial information: NCT04317534.

Implementing child and youth mental health services: early lessons from the Australian Primary Health Network Lead Site Project

Aim Primary mental health care services play an important role in prevention and early intervention efforts to reduce the prevalence and impact of mental health problems amongst young people. This paper aimed to (1) investigate whether mental health services commissioned by Australia’s 31 Primary Health Networks provided accessible care and increasingly reached children and youth across Australia, and (2) identify the challenges of, and facilitating factors to, implementing services for youth with, or at risk of, severe mental illness (i.e., youth enhanced services) in 10 PHNs which acted as mental health reform leaders (i.e., Lead Sites). Methods We used mixed methods, sourcing data from: a national minimum data set that captured information on consumers and the services they received via all 31 PHNs from 1 July 2016 to 31 December 2017; consultations with Lead Site staff and their regional stakeholders; and observational data from two Lead Site meetings. Results Many children and youth receiving services were male and up to 10% were Aboriginal and/or Torres Strait Islander young people. The majority of young people came from areas of greater disadvantage. For most children and youth receiving services their diagnosis was unknown, or they did not have a formal diagnosis. Both child and youth service uptake showed a modest increase over time. Six key themes emerged around the implementation of youth enhanced services: service access and gaps, workforce and expertise, funding and guidance, integrated and flexible service models, service promotion, and data collection, access and sharing. Conclusions Early findings suggest that PHN-commissioned services provide accessible care and increasingly reach children and youth. Learnings from stakeholders indicate that innovative and flexible service models in response to local youth mental health needs may be a key to success.

Multicentre clinical evaluation of the safety and performance of a simple transperineal access system for prostate biopsies for suspected prostate cancer: The CAMbridge PROstate Biopsy DevicE (CamPROBE) study

Objectives: To report the prospective multicentre clinical evaluation of a first-in-man disposable device, Cambridge Prostate Biopsy Device, to undertake local anaesthetic outpatient transperineal prostate biopsies. Material and methods: Disposable single-use Cambridge Prostate Biopsy devices were manufactured based on a previous prototype. The lead site developed a user training course and disseminated the method to other sites. The Cambridge Prostate Biopsy Device (CamPROBE) was offered as an alternative to transrectal ultrasound guided biopsy to men due for a biopsy as part of their clinical management. Data on safety (infections and device performance), clinical utility, patient reported experience, biopsy quality and cancer detection were collected. Procedure time and local anaesthetic use was recorded in the lead site. The study was funded by a United Kingdom National Institute for Health Research (NIHR) i4i product development award. Results: A total of 40 patients were recruited (median age 69 y) across six sites; five sites were new to the procedure. Overall, 19/40 were first prostate biopsies and 21/40 repeat procedures. Both image-targeted and systematic biopsy cores taken. There were no infections, device deficiencies or safety issues reported. The procedure was well tolerated with excellent patient-reported perception and low pain scores (median of 3, scale 0–10). Histopathology quality was good and the overall cancer diagnosis rate (first diagnostic procedures) was 68% (13/19) and for significant cancers (⩾ histological Grade Group 2), 47% (9/19). In the lead centre (most experienced), median procedure time was 25 minutes, and median local anaesthetic use 11 ml ( n=17). Conclusions: Data from this device evaluation study demonstrate that the United Kingdom-developed Cambridge Prostate Biopsy Device/method for transperineal biopsies is safe, transferable and maintains high diagnostic yields. The procedure is well tolerated by patients, suited to the local anaesthetic outpatient setting and could directly replace transrectal ultrasound guided biopsy. Level of evidence: Level III

4186 Single IRB and the CTSI: Liaison Model for the IRB Reliance Process

OBJECTIVES/GOALS: Navigating the NIH Single IRB Policy has been challenging for investigators, study teams, and Human Research Protection Programs (HRPP). In response, the Indiana Clinical and Translational Sciences Institute (CTSI) created an innovative Single IRB Project Manager role (sIRB PM), uniquely placed within the Indiana CTSI. METHODS/STUDY POPULATION: The Single IRB Project Manager role was created in 2018 by the Indiana CTSI in response to the NIH Single IRB Policy for Multi-Site Research. The role of the sIRB PM is to serve as a liaison between the Indiana University HRPP, lead site, coordinating center, and participating sites when Indiana University serves as the Single IRB. This model has proven useful to both the IRB and lead site, notably in the following ways: At study start-up, the sIRB PM can handle complicated communications among sites and the IRB at the same time the lead site is responsible for many other administrative tasks related to start-up. By absorbing the workload of IRB approval for multiple sites, the sIRB PM provides the lead site more capacity to handle other essential tasks.The sIRB PM translates new terminology and facilitates processes that are new for sites.RESULTS/ANTICIPATED RESULTS: Early assessment of this program is predominantly positive. The sIRB PM currently supports 24 external sites. In an NIA-funded 13 site study, all sites were added within 9 months of initial IRB approval of the protocol. This role fills a gap that benefits: IRB staff by allowing them to fulfill their duties of screening and review while leaving some of the reliance organization to the sIRBPM.Lead PI by allowing them to focus on conducting the research instead of the many administrative tasks required for single IRB review.Participating sites by having a liaison to enter their amendments and reportable events into an otherwise closed IRB software system.All parties by having the sIRB PM manage document organization, storage, and distribution study-wide.DISCUSSION/SIGNIFICANCE OF IMPACT: The CTSI sIRB PM role effectively shifts administrative work caused by the sIRB mandate by merging research coordinator experience with regulatory experience while building upon an existing strong relationship with the HRPP. Future focus is on process education, standardizing pricing structure, and ensuring sufficient budget support in grants.