Primary Completion Date Research Articles

GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301: a phase 3, randomized trial evaluating avutometinib plus defactinib compared with investigator’s choice of treatment in patients with recurrent low grade serous ovarian cancer

BackgroundThere are no approved treatments specifically for low grade serous ovarian cancer; current standard of care treatment options are limited in efficacy and tolerability. The combination of avutometinib with defactinib...

Evaluating the Efficacy of a Digital Therapeutic (CT-152) as an Adjunct to Antidepressant Treatment in Adults With Major Depressive Disorder: Protocol for the MIRAI Remote Study.

Major depressive disorder (MDD) is common worldwide and can be highly disabling. People with MDD face many barriers to treatment and may not experience full symptom relief even when treated. Therefore, new treatment modalities are needed for MDD. Digital therapeutics (DTx) may provide people with MDD an additional treatment option. This study aimed to describe a phase 3 remote, multicenter, randomized, masked, sham-controlled trial evaluating the efficacy of a smartphone app-based DTx (CT-152) in adult participants diagnosed with MDD, used as an adjunct to antidepressant therapy (ADT). Participants aged 22-64 years with a current primary diagnosis of MDD and an inadequate response to ADT were included. Participants were randomized 1:1 to CT-152 or a sham DTx. CT-152 is a smartphone app-based DTx that delivers a cognitive-emotional and behavioral therapeutic intervention. The core components of CT-152 are the Emotional Faces Memory Task exercises, brief lessons to learn and apply key therapeutic skills, and SMS text messaging to reinforce lessons and encourage engagement with the app. The sham DTx is a digital working memory exercise with emotionally neutral stimuli designed to match CT-152 for time and attention. Participants took part in the trial for up to 13 weeks. The trial included a screening period of up to 3 weeks, a treatment period of 6 weeks, and an extension period of 4 weeks to assess the durability of the effect. Sites and participants had the option of an in-person or remote screening visit; the remaining trial visits were remote. Efficacy was evaluated using the Montgomery-Åsberg Depression Rating Scale, the Generalized Anxiety Disorder-7, Clinical Global Impression-Severity scale, the Patient Health Questionnaire-9, and the World Health Organization Disability Assessment Schedule 2.0. The durability of the effect was evaluated with the Montgomery-Åsberg Depression Rating Scale and Generalized Anxiety Disorder-7 scale. Adverse events were also assessed. Satisfaction, measured by the Participant and Healthcare Professional Satisfaction Scales, and health status, measured by the EQ-5D-5L, were summarized using descriptive statistics. This study was initiated in February 2021 and had a primary completion date in October 2022. This represents the methodological design for the first evaluation of CT-152 as an adjunct to ADT. This study protocol is methodologically robust and incorporates many aspects of conventional pivotal pharmaceutical phase 3 trial design, such as randomization and safety end points. Novel considerations included the use of a sham comparator, masking considerations for visible app content, and outcome measures relevant to DTx. The rigor of this methodology will provide a more comprehensive understanding of the effectiveness of CT-152. ClinicalTrials.gov NCT04770285; https://clinicaltrials.gov/study/NCT04770285. RR1-10.2196/56960.

Completion Rate and Positive Results Reporting Among Immunotherapy Trials in Breast Cancer, 2004-2023

Clinical trials are the path to test and introduce new therapies in the clinic. Trials that are unable to produce results represent inefficiency in the system and may also undermine patient confidence in the new drug development process. To survey the immunotherapy clinical trial landscape of breast cancer between January 2004 and April 2023 and examine what fraction of trials with primary completion date up to November 30, 2022, failed to report outcome, assessing the proportion of trials that yielded positive results and describing trial features associated with these 2 outcomes. This cross-sectional study included breast cancer immunotherapy trials identified in ClinicalTrials.gov. Trial details and results were retrieved in December 2023. Google Scholar, PubMed, and LARVOL CLIN websites were also searched for reports. Trial outcome reported as abstract or manuscript. Reported trials were categorized as positive (ie, met its end point) or negative. Association between reporting and trial features were tested using Fisher exact test. A total of 331 immuno-oncology trials were initiated in breast cancer by April 2023; 242 trials were phase II, 47 were phase I, and 42 phase III. By setting, 212 studies (64.0%) were conducted in metastatic, 94 (28.4%) in neoadjuvant, and 25 (7.6%) in adjuvant settings. Among phase II and III trials, 168 (59.2%) were nonrandomized. One hundred twenty trials had primary completion dates up to November 30, 2022, of which 30 (25.0%; enrolling a combined 2428 patients) failed to report their outcomes; 7 phase I trials (31.8%), 21 phase II trials (23.6%), and 2 phase III trials (22.2%) were unreported. Single-center studies were significantly more likely to be unreported than multicenter studies (19 of 54 [35.2%] vs 9 of 60 [15.0%]; P = .02). Of the 90 reported trials, 47 (52.2%) and 43 (47.8%) were positive and negative, respectively. Seventeen of 19 (89.5%) of the reported randomized trials (accruing a total of 4189 patients) were negative. In this cross-sectional study of immunotherapy breast cancer trials, the large number of trials yielded modest clinical impact. Single-center trials commonly failed to report their outcomes and many phase II studies have not translated into corresponding successful phase III trials.

Implementing fragmentomics into real world screening interventions to evaluate clinical utility among individuals with elevated risk for lung cancer (FIRSTLUNG) L301.

TPS11189 Background: To optimize the impact of lung cancer screening at the healthcare system level, additional tools are needed to increase the benefits of screening. While low-dose computed tomography (LDCT) has been shown to improve lung cancer detection and reduce mortality, it is not without its risks, such as radiation exposure, false-positive results, and unnecessary interventions often leading to complications. The additional complexity of lung cancer screening is the subpar adherence to LDCT for eligible individuals, which undermines the benefits of screening. Therefore, there is a need for alternative non-invasive methodologies that exploit our understanding of the biology of cancer pathogenesis. This clinical utility study aims to observe how a non–invasive blood-based test impacts physician behavior and LDCT utilization. Methods: FIRSTLUNG 301 (NCT06145750) is a prospective, cluster randomized controlled trial (RCT) to observe the impact of the DELFI Lung cancer screening test on lung cancer screening utilization in primary care practices. Enrolled practices must meet the eligibility criteria of having a minimum of 50 actively engaged individuals in the practice eligible for lung cancer screening per the 2021 USPSTF criteria. These practices will be randomized 1:1:2 to Arm A1 (control), Arm A2 (control), or Arm B (intervention). Arm A practices will be randomized 1:1 into two groups (A1:A2) to observe the standard of care for lung cancer screening. Practices in A1 will be observed; practices in A2 will receive standard education on lung cancer screening for CME credit. Randomizing within Arms A1 and A2 aims to delineate the impact standard lung cancer screening education may have on utilization. Arm B (intervention) practices will receive education and have access to order the blood-based test for screen-eligible individuals that remained unscreened. The primary study endpoint is the proportion of practice-identified lung cancer screen-eligible individuals receiving a screening CT order and scan during the study period in the entirety of Arm A (control) versus Arm B (intervention). This RCT aims to understand the utilization and impact on lung cancer screening uptake after the DELFI blood-based test intended to inform clinical guidelines and policies focused on improving patient care and health outcomes. Progress: The study was initiated on October 31, 2023, with practice randomization. As of February 2024, the study is open for enrollment with an estimated primary study completion date of December 2025. Clinical trial information: NCT06145750 .

Delayed publication of clinical trials in gynecologic oncology

ObjectivesDelays in clinical trial publication can hinder timely implementation of evidence-based practices. We sought to determine publication rates and time to publication for clinical trials addressing gynecologic malignancies. MethodsAll clinical trials addressing gynecologic cancers in the ClinicalTrials.gov registry with a primary completion date between 1/1/2018 and 1/1/2020 were identified. The primary outcome was publication rate. All included studies had been completed for at least 3 years. Secondary outcomes were time to publication and associations between publication rate and sponsor, cancer type, and the number and location of primary study sites. ResultsOf the 290 trials included, 161 (55.5%) had a peer-reviewed publication for the primary outcome within at least 3 years after completion. Of these, 123 had positive results (76.4%) and 38 were negative (23.6%). The average duration from primary completion to manuscript publication was 23.6 months (SD 13.9; median 21.4, IQR 15.1–32.4). Only 73 had results posted on the ClinicalTrials.gov registry (25.2%). Studies with positive findings had a significantly faster time to publication than those with negative results (22.0 mo vs 29.0 mo, p = 0.009). There was no significant difference between publication rate and funding source, cancer type, or location and number of primary sites. ConclusionsTimely publication of clinical trials addressing gynecologic cancers remains an issue. Studies with positive findings were published faster than those with negative results, but the average publication time was still almost 2 years from trial completion. Further efforts should be made to identify and address barriers to clinical trial publication.

Post-approval indications and clinical trials for cardiovascular drugs: some implications of the US Inflation Reduction Act

Objective To describe the historical baseline landscape of cardiovascular drug post-approval activity, including the number and timing of post-approval clinical trials and approved indications. The US Inflation Reduction Act of 2022 (IRA) Drug Price Negotiation Program (DPNP) and its Maximum Fair Prices (MFPs) will affect incentives for investment in post-approval activity such as clinical trials for new indications. While three of the first ten drugs selected for the DPNP and MFP-setting are cardiovascular or antithrombotic drugs, limited attention has been paid to potential cardiovascular drug impacts, and to post-approval innovation. Methods For the 65 drugs originally approved by the FDA from 1995 through 2021 for a cardiovascular or antithrombotic indication (60 small molecules and 5 biologics), we develop a novel dataset of industry-sponsored, post-approval clinical trials and FDA-approved label changes for new indications. We analyze their number and timing relative to DPNP drug selection and MFP implementation dates, by drug approval-year cohort. Results We find 49% of indications were awarded and 76% of industry-funded clinical trials were completed post-approval, reaching 98% of trials for drugs in the earliest 1995–99 cohort. For the 60 small molecules, 76% of post-approval trials ended five years or more after original drug approval, 65% ended seven or more years after original drug approval (i.e. after potential DPNP selection), and 53% nine or more years after original drug approval (i.e. after potential MFP implementation). Conclusions Post-approval FDA indication approvals and clinical trial starts and primary completion dates often occurred after or near new DPNP selection and MFP implementation dates. This has economic consequences for future investment incentives. Post-approval trials for small molecules, longer-duration trials, and larger-enrollment trials, and post-approval indications focused on limited patient populations and older patients could face particular economic challenges.

Publication of Results of Registered Trials With Published Study Protocols, 2011-2022

Publishing study protocols might reduce research waste because of unclear methods or incomplete reporting; on the other hand, there might be few additional benefits of publishing protocols for registered trials that are never completed or published. No study has investigated the proportion of published protocols associated with published results. To estimate the proportion of published trial protocols for which there are not associated published results. This cross-sectional study used stratified random sampling to identify registered clinical trials with protocols published between January 2011 and August 2022 and indexed in PubMed Central. Ongoing studies and those within 1 year of the primary completion date on ClinicalTrials.gov were excluded. Published results were sought from August 2022 to March 2023 by searching ClinicalTrials.gov, emailing authors, and using an automated tool, as well as through incidental discovery. The primary outcome was a weighted estimate of the proportion of registered trials with published protocols that also had published main results. The proportion of trials with unpublished results was estimated using a weighted mean. From 1500 citations that were screened, 308 clinical trial protocols were included, and it was found that 87 trials had not published their main results. Most included trials were investigator-initiated evaluations of nonregulated products. When published, results appeared a mean (SD) of 3.4 (2.0) years after protocol publications. With the use of a weighted mean, an estimated 4754 (95% CI, 4296-5226) eligible clinical trial protocols were published and indexed in PubMed Central between 2011 and 2022. In the weighted analysis, 1708 of those protocols (36%; 95% CI, 31%-41%) were not associated with publication of main results. In a sensitivity analysis excluding protocols published after 2019, an estimated 25% (95% CI, 20%-30%) of 3670 (95% CI, 3310-4032) protocol publications were not associated with publication of main results. This cross-sectional study of clinical trial protocols published on PubMed Central between 2011 and 2022 suggests that many protocols were not associated with subsequent publication of results. The overall benefits of publishing study protocols might outweigh the research waste caused by unnecessary protocol publications.

THU070 Randomized, Placebo-controlled Phase 3 Trial Protocol Assessing The Efficacy And Safety Of Octreotide Subcutaneous Depot (CAM2029) In Patients With Acromegaly

Abstract Disclosure: D. Ferone: Advisory Board Member; Self; Recordati, Novartis-AAA, Sandoz, Camurus. Grant Recipient; Self; Bristol-Myers Squibb, Novartis-AAA, Ipsen, Camurus. Research Investigator; Self; Camurus. P. Freda: Research Investigator; Self; Camurus. L. Katznelson: Advisory Board Member; Self; Recordati, Camurus, Amryt. Research Investigator; Self; Camurus. F. Gatto: Research Investigator; Self; Camurus. A. Gilis-Januszewska: Research Investigator; Self; Camurus. M.B. Gordon: Advisory Board Member; Self; Camurus, Crinetics, HRA Pharma, Novo Nordisk, Recordati. Grant Recipient; Self; Amryt, Ascendis, Camurus, Corcept, Crinetics, Ipsen, Novartis Pharmaceuticals, Novo Nordisk, Opko, Pfizer, Inc., Strongbridge. Research Investigator; Self; Camurus. P. Kadioglu: Research Investigator; Self; Camurus. P. Maffei: Research Investigator; Self; Camurus. J.R. Seufert: Research Investigator; Self; Camurus. J. Silverstein: Advisory Board Member; Self; Amryt, Recordati. Research Investigator; Self; Camurus. J.L. Spencer-Segal: Grant Recipient; Self; Camurus. Research Investigator; Self; Camurus. M. Harrie: Employee; Self; Camurus. A. Svedberg: Employee; Self; Camurus. F. Tiberg: Employee; Self; Camurus. Extended-release formulations of the somatostatin analogues (SSAs), octreotide and lanreotide, are first-line medical therapies for patients with acromegaly who have contraindications for, or are not cured by, surgical intervention and/or radiotherapy. Treatment goals, regardless of modality, include biochemical normalization of insulin-like growth factor 1 (IGF-1) and growth hormone (GH), symptom relief, tumor control, and maintenance of pituitary function. From the patient perspective, treatment satisfaction, autonomy, and quality of life may be as important as biochemical control. Constraints of current SSA formulations include incomplete biochemical and symptom control, and a lack of convenient self-administration options. Octreotide subcutaneous (SC) depot (CAM2029) is a novel FluidCrystal® formulation of octreotide designed for easy administration by patients, in a ready-to-use prefilled syringe or injection pen. In previous clinical trials, CAM2029 provided more than five-fold higher bioavailability compared to the currently marketed long-acting octreotide formulation.The efficacy and safety of CAM2029 in acromegaly is being evaluated in a 6-month, randomized, double-blind, placebo-controlled phase 3 trial (NCT04076462). 72 patients were randomized 2:1 to monthly SC doses of CAM2029 20 mg or placebo, with the option for self-administration. Key inclusion criteria included a biochemical and clinical diagnosis of acromegaly due to a pituitary adenoma with persistent or recurrent disease, treatment with a stable dose of octreotide long-acting release or lanreotide Autogel for at least 3 months as monotherapy, and controlled disease with IGF-1 ≤1 x upper limit of normal (ULN). Key exclusion criteria included GH ≥2.5 μg/L at screening, pituitary surgery within 6 months of screening, prior pituitary irradiation, and recent treatment with pasireotide, pegvisomant, or dopamine agonists. The primary endpoint is the proportion of patients with normalized IGF-1 (≤1 x ULN) after 6 months of treatment. Other endpoints include change from baseline of IGF-1, GH and patient-reported outcomes (Treatment Satisfaction Questionnaire for Medication, Self-Injection Assessment Questionnaire, Acromegaly Quality of Life Questionnaire, EQ-5D-5L), safety and tolerability, clinical signs and symptoms of acromegaly, use of rescue medication and octreotide pharmacokinetics. The estimated primary completion date for the trial is May 2023. After completing study treatment, patients may switch to open-label treatment in a phase 3 long-term safety and extension trial of CAM2029 (NCT04125836). Presentation: Thursday, June 15, 2023

Tralokinumab Efficacy Over 1Year in Adults with Moderate-to-Severe Atopic Dermatitis: Pooled Data from Two Phase III Trials.

Two phase III trials, ECZTRA 1 and 2, confirmed the efficacy and safety of tralokinumab versus placebo in adults with moderate-to-severe atopic dermatitis (AD). To further explore the long-term efficacy of tralokinumab for AD, a pooled analysis of these trials was conducted. ECZTRA 1 and 2 patients (n = 1596 total) were randomized to tralokinumab 300mg or placebo every 2weeks (q2w) over 16weeks. Patients achieving Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) and/or 75% improvement in the Eczema Area and Severity Index (EASI-75) at Week 16, were re-randomized to tralokinumab q2w, every 4weeks (q4w), or placebo (tralokinumab withdrawal) for another 36weeks. Patients not achieving the response criteria at Week 16 received open-label tralokinumab q2w plus optional topical corticosteroids (TCS). A pooled, prespecified analysis assessed the proportions of Week 16 responders that maintained IGA 0/1 and/or EASI-75 at Week 52. Pooled data from all patients initiated with tralokinumab, regardless of the response at Week 16 or dosing regimen received thereafter, were analyzed post hoc. In patients who achieved the primary endpoints at Week 16, IGA 0/1 responses were maintained at Week 52 without rescue treatment (including TCS) by 55.9%, 42.4%, and 34.0% of patients re-randomized to tralokinumab q2w, q4w, or placebo (tralokinumab withdrawal), respectively, while EASI-75 responses were maintained by 57.3%, 50.4%, and 26.4%, respectively (prespecified analysis). In a post hoc analysis of all patients initiated with tralokinumab, response rates improved over time with continued tralokinumab treatment beyond Week 16 to Week 52 for EASI-50 (63.1-82.7%), EASI-75 (37.6-61.8%), EASI-90 (20.4-37.3%), and IGA 0/1 (23.0-36.2%). Tralokinumab treatment provides progressive and sustained improvement over 1 year in the extent and severity of AD in patients with moderate-to-severe AD. NCT03131648 (ECZTRA 1); study start date: 30 May 2017; primary completion date: 7 August 2018; study completion date: 10 October 2019. NCT03160885 (ECZTRA 2); study start date: 12 June 2017; primary completion date: 4 September 2019; study completion date: 14 August 2019. INFOGRAPHIC.

Posting of clinical trial results and other critical information from completed medicines trials on ClinicalTrials.gov.

Clinical trials transparency requires trial registration and the posting of results on a public register. US regulations also require the posting of protocols and statistical analysis plans (SAPs). For US Federal agency funded trials to be started on or after 21January2019, informed consent forms (ICFs) must also be posted. Posting these documents is not mandatory in other countries. We aimed to assess compliance with US regulations of trials conducted in the US or in other countries with respect to ICFs, protocols, SAPs, and results. This cross-sectional analysis (27April2023) comprised completed medicines trials to be started on or after 21January2019 registered on ClinicalTrials.gov. Trial data were registered by funder type (i.e., 'US federal agencies', industry, and 'all others') and development phase. Of 5,584 trials, 40% were conducted solely in the US. 47% and 12% of US and non-US trials had posted results. Some 40% of US trials had posted protocols and SAPs as did 9% of trials conducted in other countries. Only 10% (US) and 2% (other countries) of trials had posted ICFs. When the margin of the last 2 and 12 months after primary completion date were considered in the analysis, ICF posting rate did not change, but posting results increased to 64% for US trials. 'US Federal agencies' funded trials were significantly more likely to post ICFs than industry [OR 23.9 (12.5-45.7; <.001)] or 'all others' [OR 3.16 (1.79-5.56; <.001)]. Future interventions should be considered to encourage timely posting of trial results and information.

TIPS-05 ADJUVANT TEMOZOLOMIDE CHEMOTHERAPY FOLLOWING RADIOTHERAPY IN NEWLY DIAGNOSED LOW-GRADE GLIOMA PATIENT WITH RESIDUE TUMORS: A MULTICENTER, OPEN LABEL, RANDOMIZED TRIAL

Abstract Low-grade glioma (LGG) with infiltrative nature and frequent growth in eloquent area in brain often makes total resection impossible. Although post-radiation adjuvant temozolomide (TMZ) is the standard of care for high-grade gliomas, and radiotherapy and/or TMZ are recommended for the treatment of residue low-grade gliomas, the efficacy of combined radiotherapy with adjuvant TMZ for residue LGG remains to be defined. We have initiated a randomized clinical trial in 2012 to test whether radiotherapy with subsequent TMZ chemotherapy will improve survival of patients with residue LGG compared to radiotherapy alone. This study was approved by the Ethics Committee of the Sun Yat-sen University Cancer Center, Guangzhou, China (approval No. 5010-2012-03) and was registered with ClinicalTrials.gov (NCT01649830). Inclusion Criteria: Patients age of 18 years to 60 years, with incompletely resected supratentorial WHO grade 2 astrocytoma, oligodendroglioma or oligodendroastrocytoma. Enrolled patients were randomized into: radiation therapy alone (RT) or radiotherapy with subsequent TMZ chemotherapy (RC) group. Start Date: July 2012, Estimated Primary Completion Date:August 2025. Radiation therapy will start within 8 weeks after neurosurgical procedures, with a total dose of 54.0 Gy in 27 - 30 fractions over 6 - 7 weeks. Four weeks after radiotherapy, patients in RC group will receive 6 cycle of TMZ dosed at 200 mg/m2 daily for 5 consecutive days, repeated every 28 days. We have completed enrollment on December 2018 with valid cases of 248 patients. Up to last follow-up date of Feb. 2023, 204 cases were analyzed (see table). There is no significant difference between RT group and RC group on both PFS and OS (5-year PFS 68.9% vs 75.2%, p=0.680; 5-year OS 92.0% vs 86.0%, p=0.400). Longer follow-up and molecular subgroup analysis are currently on the way, which could show benefit in special molecular subgroup.

Secukinumab in Pediatric Patients with Plaque Psoriasis: Pooled Safety Analysis from Two Phase 3 Randomized Clinical Trials.

Plaque psoriasis affects ~ 1% of the pediatric population, negatively impacting quality of life. The efficacy and safety of secukinumab in pediatric patients with moderate to severe or severe chronic plaque psoriasis have been established in two pivotal phase 3 trials (open-label, NCT03668613; double-blind, NCT02471144). The aims were to report the pooled safety of secukinumab up to 52 weeks from two studies in subgroups of pediatric patients stratified by age and bodyweight, and to present, alongside the pediatric data, the pooled safety data from four pivotal adult secukinumab trials. The safety of secukinumab was evaluated in subgroups of pediatric patients defined by age (6 to <12 and 12 to <18 years) and bodyweight (<25 kg, 25 to <50 kg, and ≥50 kg) in the pooled population. Patients received secukinumab low dose (LD; 75/75/150 mg), secukinumab high dose (HD; 75/150/300 mg), placebo, or etanercept (0.8 mg/kg). For safety analyses, data were pooled from the pediatric studies NCT03668613 and NCT02471144, and presented alongside the pooled data from four adult pivotal studies (NCT01365455, NCT01636687, NCT01358578, NCT01555125). A total of 198 pediatric patients (overall exposure: 184.6 patient-years [PY]) and 1989 adult patients (1749.5 PY) receiving secukinumab up to week 52 were included in this analysis. At week 52, the incidence of adverse events (AEs) was lower in the lower age and bodyweight subgroups. The AEs reported within these subgroups were consistent with the overall AEs reported in this analysis. Overall, exposure-adjusted incidence rates for treatment-emergent AEs were lower in the secukinumab-treated pediatric pool (198.8/100 PY) compared with the etanercept (266.3/100 PY) and adult pools (256.1/100 PY). Up to 52 weeks, the incidence rates of the AEs in the secukinumab-treated patients in the 6 to <12 years subgroup and 12 to <18 years subgroup were 167.7/100 PY and 214.7/100 PY, respectively. Similarly, incidence rates of the AEs in the secukinumab-treated patients in the <25 kg, 25 kg to <50 kg, and ≥50 kg subgroups were 177.3/100 PY, 192.5/100 PY, and 206.8/100 PY, respectively. Nasopharyngitis was the most frequently reported AE in secukinumab-treated pediatric patients across age (<12 years: 11.8/100 PY; ≥12 years: 42.4/100 PY) and bodyweight (<25 kg: 22.8/100 PY; 25 kg to <50 kg: 19.0/100 PY; ≥50 kg: 43.0/100 PY). Of the 198 secukinumab-treated pediatric patients, one reported nail Candida, one reported skin Candida, and two reported vulvovaginal Candida. Transient and mostly mild events of neutropenia were observed with secukinumab, none leading to study treatment discontinuation. No incidence of treatment-emergent anti-drug antibodies was reported in pediatric patients treated with secukinumab. Secukinumab was well tolerated in pediatric patients with moderate to severe and severe plaque psoriasis across age and bodyweight subgroups. The overall safety profile of secukinumab in pediatric patients was consistent with that of adult patients. NCT03668613 (Novartis Study Code CAIN457A2311, referred to as A2311), actual study start date: August 29, 2018; actual primary completion date: September 19, 2019; estimated study completion date: September 14, 2023. NCT02471144 (Novartis Study Code CAIN457A2310, referred to as A2310), study start date: September 29, 2015; primary completion date: December 13, 2018; estimated study completion date: March 31, 2023.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) typically have poor outcomes following standard treatment. Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca), an antibody-drug conjugate (ADC) comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine (PBD) dimer toxin, received accelerated (US) and conditional (EU) approval in R/R DLBCL after ≥2 lines of systemic therapy, based on data from the phase 2 LOTIS-2 trial (Caimi PF et al. Lancet Oncol. 2021;22[6]:790). Rituximab (R), an anti-CD20 monoclonal antibody, is part of standard immunotherapy for DLBCL, both as frontline therapy and in subsequent treatments. Preclinical evidence suggests the addition of R to anti-CD19 ADC therapy may result in prolonged tumor control (Ryan MC et al. Blood. 2017;130[18]:2018). LOTIS-5 aims to evaluate Lonca-R vs standard immunotherapy of R + gemcitabine + oxaliplatin (R-GemOx) in R/R DLBCL. Methods: This is a phase 3, randomized, open-label, 2-part, 2-arm, multicenter study of Lonca-R in patients with R/R DLBCL (NCT04384484). The study consists of a safety run-in phase with Lonca-R (part 1) and a randomized phase evaluating efficacy and safety of Lonca-R vs R-GemOx (part 2). Approximately 350 patients will be enrolled across both parts: part 1 has completed; part 2 will enroll approximately 330 patients (randomized 1:1) to achieve 262 events for the primary end point analysis of progression-free survival by independent central review. Secondary end points include overall survival, overall response rate (2014 Lugano classification), complete response rate, duration of response, frequency and severity of adverse events, change from baseline in laboratory values, concentration and pharmacokinetic parameters of Lonca (conjugated and total antibody and unconjugated PBD), and changes in patient-reported outcomes from baseline. The dosing regimen for Lonca-R is Lonca 150 μg/kg + rituximab 375 mg/m2 every 3 weeks (Q3W) for 2 cycles, then Lonca 75 μg/kg + rituximab 375 mg/m2 Q3W for up to 6 cycles. The dose regimen of R-GemOx is rituximab 375 mg/m2, gemcitabine 1000 mg/m2, and oxaliplatin 100 mg/m2 every 2 weeks for up to 8 cycles. Key eligibility criteria include age ≥18 years, pathologic diagnosis of DLBCL (including patients with DLBCL transformed from indolent lymphoma) or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, ≥1 line of prior systemic therapy, previous stem cell transplant >30 days (autologous) or >60 days (allogenic) prior to start of study drug or stem cell transplant ineligibility, and measurable disease. The randomized part of LOTIS-5 began in January 2022 and has an estimated primary completion date of June 2025; enrollment continues, with a total of 45 active sites across the US, Canada, Spain, France, Belgium, Italy, Switzerland, Czech Republic, Poland, and China. The research was funded by: ADC Therapeutics SA; medical writing: CiTRUS Health Group Keywords: molecular targeted therapies, combination therapies, ongoing trials Conflicts of interests pertinent to the abstract C. Carlo-Stella Consultant or advisory role ADC Therapeutics, Celgene/Bristol Myers Squibb, Karyopharm, Novartis, Sanofi, Roche, Merck Sharp & Dohme, Scenic Biotech Honoraria: Merck Sharp & Dohme, Janssen Oncology, AstraZeneca, Celgene, Incyte, Gilead Sciences, Roche M. Chung Stock ownership: The Oncology Institute A. Stathis Honoraria: Eli Lilly, Bayer, Roche, Novartis, Janssen Oncology, AstraZeneca Research funding: ADC Therapeutics , Pfizer, Roche, Novartis, Bayer, Eli Lilly, MEI Pharma, Cellestia, Debiopharm Group, Merck/MSD, Abbvie, Amgen, AstraZeneca, Incyte, Loxo, Philogen Y. Wang Employment or leadership position: ADC Therapeutics Stock ownership: Johnson and Johnson (Family Member) L. Wang Employment or leadership position: ADC Therapeutics M. Hamadani Consultant or advisory role AbGenomics, ADC Therapeutics, Celgene, Incyte, Janssen R&D, Omeros, Pharmacyclics, TeneoBio, Verastem Research funding: Astellas Pharma, Spectrum Pharmaceuticals, Takeda Other remuneration: Speakers’ bureau for AstraZeneca, BeiGene, Sanofi Genzyme

SA8 Public Disclosure of Clinical Research Is an Important Factor for Evidence-Based Decision-Making: Is the Current Evidence Being Disclosed in a Timely Manner?

According to World Health Organization, the main findings of clinical trials should be submitted for publication, preferably open access, in a peer-reviewed journal within 12 months of study completion. The Food and Drug Administration Amendments Act mandates reporting summary results in the database of ClinicalTrials.gov within 12 months of study completion. We therefore assessed the proportion of completed trials on psoriasis that have publicly disclosed the primary results within 2 years of primary completion date, either as a publication or on ClinicalTrials.gov.

A Phase 2/3 Placebo-Controlled, Parallel Group, Randomized Withdrawal Study to Evaluate the Efficacy and Safety of Nipocalimab for Adults with Chronic Inflammatory Demyelinating Polyneuropathy: the ARISE study (P14-8.006)

<h3>Objective:</h3> Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare, chronic autoimmune disease of the peripheral nervous system characterized by progressive weakness and impaired sensation. The ARISE study (NCT05327114) is a Phase 2/3 multicenter, double-blind, placebo-controlled, randomized withdrawal study evaluating the efficacy and safety of nipocalimab in adults with CIDP. <h3>Background:</h3> Nipocalimab is a fully human aglycosylated immunoglobulin (Ig)G1 monoclonal antibody (mAb) designed to selectively bind, saturate, and block the IgG binding site on the endogenous neonatal Fc receptor. Nipocalimab is administered via intravenous infusion. <h3>Design/Methods:</h3> The study consists of the following periods: (1) Screening (≤4 weeks)/Run-in (≤12 weeks), which includes identification of patients with active CIDP; (2) Stage A (Open-label, 12 weeks), in which participants receive nipocalimab loading dose, then once every 2 weeks (q2w); (3) Stage B (Double-blind, placebo-controlled, ≤52 weeks), in which participants are randomized 1:1 to nipocalimab q2w versus placebo; (4) Open-label extension (variable duration), in which participants receive nipocalimab q2w. Key inclusion criteria include adults ≥18 years with CIDP, progressing/relapsing forms, confirmed by independent adjudication committee; CIDP disease activity score ≥3; and adjusted INCAT disability score 2–9. Patients with pure sensory CIDP or CISP, or other diagnoses that could better explain their clinical presentation are excluded. The primary endpoint is time to first occurrence of a relapse event in Stage B. Secondary efficacy endpoints include time to initial response to nipocalimab and percentage of nipocalimab responders in Stage A, and change from baseline in functional measures (e.g. grip strength, MRC sum score, etc.) in Stage B. Other secondary endpoints include safety/tolerability, pharmacokinetics, immunogenicity, and pharmacodynamics of nipocalimab. <h3>Results:</h3> The study is currently enrolling patients, targeting approximately 300 patients, with primary study completion date anticipated in 2026. <h3>Conclusions:</h3> This ongoing phase 2/3 study will assess the efficacy, safety, PK, and PD of nipocalimab in adults with CIDP. <b>Disclosure:</b> Dr. Ford has received personal compensation for serving as an employee of Janssen . Dr. Ford has stock in Janssen. Dr. Wong has received personal compensation for serving as an employee of Janssen Research &amp; Development. Dr. Wong has received personal compensation for serving as an employee of Biogen. Dr. Wong has stock in Biogen. Dr. Youssef has received personal compensation for serving as an employee of Janssen. Dr. Youssef has stock in Janssen. Mr. Murray has received personal compensation for serving as an employee of Janssen. Dr. Lim has received personal compensation for serving as an employee of Johnson &amp; Johnson. Dr. Lim has stock in Johnson &amp; Johnson. Dr. Nobile-Orazio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ArgenX, Belgium. Dr. Nobile-Orazio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for LFB, France. Dr. Nobile-Orazio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche, Switzerland. Dr. Nobile-Orazio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CSL Behring. Dr. Nobile-Orazio has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen, USA. The institution of Dr. Nobile-Orazio has received research support from Takeda/Shire. Ingemar Merkies has nothing to disclose. Dr. Cornblath has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Octapharma. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Annexon. Dr. Cornblath has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pfizer. Dr. Cornblath has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Grifols. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cigna. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Anavex. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hansa. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MPTP. Dr. Cornblath has received intellectual property interests from a discovery or technology relating to health care. Dr. Sun has received personal compensation for serving as an employee of Janssen.

Completion and publication of clinical trials in a cooperative group: a cohort study of trials of the Swiss Group for Clinical Cancer Research (SAKK)

BackgroundPremature trial discontinuation and non-publication of trial results are still major issues negatively affecting reliable evidence generation.ObjectivesTo investigate trial completion and publication rate of cancer trials conducted within the Swiss...

Abstract OT2-18-03: Neoadjuvant anlotinib plus nab-paclitaxel based chemotherapy in patients with HER2-negative breast cancer: A prospective, single-arm, single-center, phase II clinical study

Abstract BACKGROUND: Antiangiogenic agent plus neoadjuvant chemotherapy confers an improvement in pathological complete response (pCR) rate among patients with HER2-negative breast cancer. Anlotinib is a novel multi-target tyrosine kinase inhibitor that effectively inhibit VEGFR, FGFR, c-KIT, c-MET, and RET. This phase II study aims to evaluate the efficacy and safety of anlotinib combined with chemotherapy as neoadjuvant treatment in HER2-negative breast cancer. PATIENTS AND METHODS: Eligible patients (pts) were women, aged 18-70 years, ECOG status 0-2, previously untreated HER2-negative breast cancer. The HER2-negative, defined as immunohistochemistry of 0, 1+, and 2+/ISH-. Pts were required to have a palpable primary tumor at least 200mm in diameter in the breast, as assessed by physical examination, and to be classified as having tumor stage T1c to T3, nodal stage N0 to N2a, and metastasis stage M0. Thirty pts will be enrolled and received 5 cycles of anlotinib (12 mg qd, d1-14; 21 days per cycle) plus 6 cycles of nab-paclitaxel (200 mg/m2, once every 3 weeks), anthracycline (pirarubicin 50 mg/m2) and cyclophosphamide at 500 mg/m2, followed by surgery. The primary endpoint is pCR rate (ypT0/Tis ypN0) and the secondary endpoints include disease-free survival (DFS), overall survival (OS), and safety. The study was initiated in August 2021.This study is currently open and 10 patients had been enrolled. The estimated primary completion date is October 1, 2023. Results: The trail is in progress. Conclusion: The trail is in progress. Citation Format: Jing Fan, Ting Wang, Huimin Meng, Songpeng Li, Jing Kong, Yidi Wang. Neoadjuvant anlotinib plus nab-paclitaxel based chemotherapy in patients with HER2-negative breast cancer: A prospective, single-arm, single-center, phase II clinical study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-18-03.

PP18 Horizon Scanning For Clinical Biosimilar Medicines: Informing The Lifecycle Of Health Technology Assessment And Market Access

IntroductionThe National Institute for Health and Care Research (NIHR) Innovation Observatory (IO) national horizon scanning research centre, has a remit to notify its stakeholders, including the National Institute for Health and Care Excellence (NICE), about innovative interventions; including biosimilar medicines in the pipeline. Biosimilar medicines bypass many developmental steps, making them substantially cheaper to manufacture for providers, which increases market availability and improves treatment access for patients.MethodsSince 2017, the NIHR IO has monitored biosimilars in clinical development that align to the NICE health technology assessment remit. The data set explored was exported from our internal medicines innovation database - MInD.Data sets were created that included information on the characteristics of biosimilars and their associated clinical trials. Analyses and visualization creation were carried out using Microsoft Excel and Microsoft Power BI.ResultsA total of 100 unique biosimilar medicines in 136 clinical trials were included in the MInD since April 2017. Of these, 44 percent of biosimilars are currently EMA-approved (Nov 2021). Adalimumab was the reference medicine with the most unique biosimilars identified (12%). Seventy-two percent of the biosimilars in MInD were indicated for non-oncology conditions, twenty percent for oncology condition and eight percent for both.There were 46 biosimilars unapproved, which were in active development. Of these biosimilars 17.4 percent are indicated for an oncology condition, 78.3 percent for non-oncology conditions, and 4.3 percent for biosimilars for both. Aflibercept was the reference product with the most (eight) biosimilars in active development.There were 56 individual clinical trials in the MInD that list a biosimilar in development. For 26 trials, the primary completion date (PCD) was prior to 2021, whilst 28 trials listed a PCD post-2021, and 2 PCD’s were unavailableConclusionsOur analysis identified high levels of active clinical development for biosimilars. The majority of biosimilars being developed are indicated for non-oncology conditions, with many in trials due to readout in the near future. Early identification, monitoring and reporting of biosimilars allows for expedited patient access and benefits, including cost-savings for health services.This study is funded by the National Institute for Health Research (NIHR) [(HSRIC-2016-10009)/Innovation Observatory].

Intravitreal aflibercept for the treatment of patients with neovascular age-related macular degeneration in routine clinical practice in Latin America: the AQUILA study

BackgroundAQUILA (NCT03470103) was a prospective, observational, 12-month cohort study evaluating treatment patterns, clinical effectiveness, and safety of intravitreal aflibercept (IVT-AFL) in patients from Latin America with neovascular age-related macular degeneration (nAMD).MethodsTreatment-naïve and previously treated (switching to IVT-AFL) patients (aged ≥ 55 years) were enrolled from March 2018, with a primary completion date of September 2020, from Argentina, Colombia, Costa Rica, and Mexico. Patients received IVT-AFL in a routine clinical practice setting.ResultsOf 274 patients in the full analysis set, 201 were treatment-naïve and 73 had received previous treatment. The mean ± standard deviation number of IVT-AFL injections received by month 12 was 4.2 ± 1.9 (treatment-naïve) and 5.2 ± 2.7 (previously treated). The median duration from diagnosis to IVT-AFL treatment was 1.2 months (treatment-naïve) and 19.5 months (previously treated). Mean best-corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] letters) improved from baseline to month 12 by + 5.2 ± 18.3 (treatment-naïve; baseline: 48.2 ± 23.5) and + 3.1 ± 15.3 letters (previously treated; baseline: 47.7 ± 21.4).ConclusionAQUILA is the first study to assess the use of IVT-AFL in routine clinical practice in Latin America. Mean BCVA and other visual acuity outcomes improved in both treatment groups, despite many patients not receiving the IVT-AFL label-recommended regimen of three initial monthly doses, or seven or more injections in 12 months. Patients who did receive the label-recommended number of injections had numerically greater improvements in visual acuity outcomes. Patients with nAMD treated regularly and more frequently with IVT-AFL, therefore, have the potential to achieve outcomes consistent with those observed in interventional studies.Trial registration: Clinicaltrials.gov, NCT03470103. Registered February 5, 2018, https://clinicaltrials.gov/ct2/show/NCT03470103

1368P TALAPRO-1: Talazoparib monotherapy in metastatic castration-resistant prostate cancer (mCRPC) with DNA damage response alterations (DDRm) – Exploration of tumor genetics associated with prolonged benefit

TALAPRO-1 enrolled men with progressive mCRPC, measurable soft-tissue disease, and tumor DDRm involved directly or indirectly in homologous recombination repair (11-gene panel). Enrolled men had received 1–2 taxane-based chemotherapy regimens and progressed on ≥1 novel hormonal therapy. Confirmed objective response rate (primary endpoint; per RECIST 1.1; blinded independent central review [BICR]) was 29.8%. The molecular bases of prolonged clinical benefit with poly(ADP-ribose) polymerase inhibitors are incompletely understood, although limited evidence suggests that patients exhibiting large deletions in BRCA genes may experience extended benefit. Exploratory post hoc biomarker analyses assessed tumor genetics associated with prolonged antitumor benefit in TALAPRO-1. Tumor alterations were assessed using FoundationOne®CDx. Zygosity of tumor alterations was predicted using somatic-germline-zygosity. Prolonged benefit was assessed as radiographic progression-free survival ([rPFS]; RECIST 1.1/PCWG3; BICR) time to event or censoring. Data cutoff was Sept 4, 2020 (primary completion date). Of 104 men in the efficacy population, 16 had rPFS of ≥12 months. Of their 16 tumors, 15 (94%) had BRCA2 alterations, including 10 large structural variants (9 copy number loss, 1 rearrangement) and 5 short variants (SV; 4 homozygous). In contrast, only 6/27 (22%) men with rPFS <2.0 months exhibited BRCA2 alterations (1 rearrangement, 1 non-defined, and 4 SV with 2 homozygous). Of 61 men with rPFS <12 months but ≥2 months, 36 (59%) had BRCA2 alterations (9 copy number loss, 1 rearrangement, 21 SV [11 homozygous], 2 multiple alterations [1 homozygous], and 3 not defined). Conversely, TP53 alterations were less common for men with rPFS ≥12 months vs <2 months (2/16 vs 14/27; P=0.02 Fisher’s exact test, 2-tails), potentially reflecting negative prognosis or a subgroup less sensitive to PARP inhibition. Based on these retrospective, exploratory analyses of TALAPRO-1, men exhibiting prolonged benefit typically exhibited BRCA2 copy number loss or homozygous alterations, and lacked TP53 alterations.