Single Trial Research Articles

Two single arm trials of AKL-T01, a digital therapeutic for adolescents and adults with ADHD

Inattention symptoms represent a key driver of functional impairment in ADHD and often persist into adolescence and adulthood, underscoring a need for novel treatments targeting attentional control. We evaluated AKL-T01—a digital therapeutic that is FDA-cleared for children 8–12 y with ADHD—in adolescents and adults with ADHD in two independent single-arm trials: STARS-ADHD-Adolescent, a 4-week trial in adolescents 13–17 y (n = 162 enrolled), and STARS-ADHD-Adult, a 6-week trial in adults 18 and older (n = 221 enrolled). AKL-T01 was linked with improvements on the Test of Variables of Attention (TOVA®) Attention Comparison Score (ACS) of 2.6 (95% CI: 2.02, 3.26; p < 0.0001) in adolescents and 6.5 in adults (95% CI: 5.35, 7.57; p < 0.0001), along with improvements in secondary endpoints. 15 participants reported adverse device effects, all mild or moderate. Though limited by a single-arm design, results provide preliminary support for the safety and efficacy of AKL-T01 for adolescents and adults with ADHD.

1859-LB: PG-102, a Novel Bispecific GLP-1R/GLP-2R Fc-Fused Agonist—Data on Safety, Tolerability, and Pharmacokinetics (PK) in Single Ascending Dose Trial in Healthy Subjects and Preliminary Population PK Modeling

1859-LB: PG-102, a Novel Bispecific GLP-1R/GLP-2R Fc-Fused Agonist—Data on Safety, Tolerability, and Pharmacokinetics (PK) in Single Ascending Dose Trial in Healthy Subjects and Preliminary Population PK Modeling

Feasibility and acceptability of an acceptance and commitment therapy for caregivers of dementia: a single arm trial emphasizing adult protection

PurposeCaregivers for older adults play a crucial role in protecting those diagnosed with dementia. These caregivers often experience heightened anxiety, depression and burdens associated with their responsibilities. Sufficient support and efficient coping mechanisms alleviate distress and caregiving burdens, thereby enhancing and protecting adults. Acceptance and commitment therapy (ACT) fosters acceptance of internal experiences and promotes behaviors aligned with personal values. This single-arm pilot study aims to evaluate the feasibility, acceptability and preliminary effects of an online ACT intervention (Online Acceptance and Commitment Therapy Intervention for Caregivers [OACTIC]) on well-being aspects among dementia caregivers, emphasizing the importance of tailored interventions to protect older adults and their caregivers.Design/methodology/approachThe caregiver must be ≥21 years of age (i.e. a parent, spouse, partner, sibling or adult child), or they must be the primary caregiver of older adults with dementia for ≥12 months and have scores that indicate moderate or higher on the scale of anxiety, depression and poor quality of life. Participants received an online-based ACT over six weekly 1-h sessions. The following outcome measures were administered at baseline (T1), immediately post-intervention (T2) and three-month follow-up (T3): Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Zarit Burden Interview, The Experience of Suffering Measure and Acceptance and Action Questionnaire-II.FindingsAll 45 participants completed the study, with 93.3% rating their OACTIC experience as “completely satisfied.”Originality/valueOACTIC (Trial Registration# AEARCTR-0012366) is a novel study conducted in Pakistan, offering a cost-effective and time-efficient treatment approach that enhances the psychological well-being and protects older adults and their caregivers.

Pharmacometrics-Enabled DOse OPtimization (PEDOOP) for seamless phase I-II trials in oncology

ABSTRACT We consider a dose-optimization design for a first-in-human oncology trial that aims to identify a suitable dose for late-phase drug development. The proposed approach, called the Pharmacometrics-Enabled DOse OPtimization (PEDOOP) design, incorporates observed patient-level pharmacokinetics (PK) measurements and latent pharmacodynamics (PD) information for trial decision-making and dose optimization. PEDOOP consists of two seamless phases. In phase I, patient-level time-course drug concentrations, derived PD effects, and the toxicity outcomes from patients are integrated into a statistical model to estimate the dose-toxicity response. A simple dose-finding design guides dose escalation in phase I. At the end of the phase I dose finding, a graduation rule is used to assess the safety and efficacy of all the doses and select those with promising efficacy and acceptable safety for a randomized comparison against a control arm in phase II. In phase II, patients are randomized to the selected doses based on a fixed or adaptive randomization ratio. At the end of phase II, an optimal biological dose (OBD) is selected for late-phase development. We conduct simulation studies to assess the PEDOOP design in comparison to an existing seamless design that also combines phases I and II in a single trial.

REDOMA: Bayesian random-effects dose-optimization meta-analysis using spike-and-slab priors.

The rise of cutting-edge precision cancer treatments has led to a growing significance of the optimal biological dose (OBD) in modern oncology trials. These trials now prioritize the consideration of both toxicity and efficacy simultaneously when determining the most desirable dosage for treatment. Traditional approaches in early-phase oncology trials have conventionally relied on the assumption of a monotone relationship between treatment efficacy and dosage. However, this assumption may not hold valid for novel oncology therapies. In reality, the dose-efficacy curve of such treatments may reach a plateau at a specific dose, posing challenges for conventional methods in accurately identifying the OBD. Furthermore, achieving reliable identification of the OBD is typically not possible based on a single small-sample trial. With data from multiple phase I and phase I/II trials, we propose a novel Bayesian random-effects dose-optimization meta-analysis (REDOMA) approach to identify the OBD by synthesizing toxicity and efficacy data from each trial. The REDOMA method can address trials with heterogeneous characteristics. We adopt a curve-free approach based on a Gamma process prior to model the average dose-toxicity relationship. In addition, we utilize a Bayesian model selection framework that uses the spike-and-slab prior as an automatic variable selection technique to eliminate monotonic constraints on the dose-efficacy curve. The good performance of the REDOMA method is confirmed by extensive simulation studies.

HDAC I/IIb selective inhibitor purinostat mesylate in relapsed and refractory diffuse large B-cell lymphoma: A single agent phase IIa trial.

LBA7074 Background: Relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) has a poor prognosis. Double-expressor (DEL) or TP53 abnormal r/r DLBCL patients(pts) are associated with even worse outcomes. Class I and IIb histone deacetylases (HDACs) are overexpressed in DLBCL and have been identified as a therapy target. Purinostat Mesylate (PM) is a high selective HDAC I/IIb inhibitor. Phase I dose-escalation trial of PM (1.2, 2.4, 4.0, 6.0, 8.4, 11.2, 15 mg/m2) by i.v was conducted in 29 hematologic malignancies at day 1, 4, 8, 11 of a 21-day cycle. PM was generally well tolerated with no DLTs. 61.1% (11/18) ORR was observed in r/r lymphoma pts. Based on these data, we conducted a phase 2a to further explore efficacy and safety of PM and mechanism of actions. Methods: This randomized, multicenter, open-label, phase 2a study was conducted from Nov.2022 to the present(NCT05563844). Key eligibility include r/r DLBCL pts with prior therapy including anti-CD20 antibody and anthracycline-based chemotherapy; ECOG≤2. Thirty pts were randomized 1:1 received PM at 8.4 and 11.2 mg/m2 on Day 1, 4, 8, 11 of a 21-day cycle. Pts continued to receive PM until disease progression or unacceptable toxicity. Primary outcome was ORR and safety. Multiple cell lines and PDX mouse models were used to evaluate the PM activity and mechanism of action in vitro and in vivo. ATAC-seq, bulk RNA-seq, and scRNA-seq from both PDX models and pts were investigated for the activated immune response of PM. Results: Thirty patients were enrolled and 28 patients were evaluable. The ORR (20/28) was 71.4% (95%CI:51.3-86.8) with 5 CR and 15 PR. Fifteen pts at 8.4 mg/m2 achieved an ORR of 66.7%(95%CI:38.4-88.2) with 1 CR and 9 PR. Thirteen pts at 11.2 mg/m2 achieved ORR of 76.9%(95%CI:46.2-95.0) with 4 CR and 6 PR. As of the data cut off in Feb. 2024, 7 pts remained on treatment and the longest treatment has lasted 17 cycles. Median PFS was 4.3m (95%CI:2.8-8.5), OS were immature. In subgroup analyses, 7 DE DLBCL pts obtained 42.9%(3/7) ORR and 11 pts with TP53 abnormal by FISH or NGS test achieved 45.5%(5/11) ORR. Fifteen pts with non-DE or without TP53 abnormal achieved ORR of 86.7%(13/15). The most frequently reported Grade≥3 TRAE were thrombocytopenia, neutropenia, lymphocytopenia. No PM-related death was reported. PM monotherapy showed stronger and superior antitumor effects in DE DLBCL and TP53 mutations PDX models than selinexor and R-CHOP. PM significantly down-regulates the proteins c-MYC, EZH2, and mutated P53. ATAC-seq, bulk RNA-seq and scRNA-seq revealed that PM can stimulate the proliferation and activation of cytotoxic T cells and NKT cells, up-regulate the expression of B-cell tumor MHC I and II and inhibit tumor cell immune escape. Conclusions: This study further supports the recommended dose 11.2 mg/m2 PM as the phase 2b for r/r DLBCL. Currently, the phase 2b, open-label, multicenter study has enrolled in 37 sites in China. Clinical trial information: NCT05563844 .

Improving Prediction of Severity of Sepsis in Children: A Single Center trial

Improving Prediction of Severity of Sepsis in Children: A Single Center trial

Time to sense biofield (Prana) experiences between hands: A preliminary single blinded randomized placebo controlled trial

Aims There is minimal research on the duration of biofield experiences. This preliminary study used the experiential learning practice of Master Choa Kok Sui's hands sensitisation to determine the duration to experience biofield sensations in between hands and to find the relationship between learning style preferences and biofield sensations. Methods This randomized placebo controlled, single blinded trial included 88 male and female pre-service teachers, aged 22.8±1.2 years. Participants completed a ruler drop test for reaction time, and Six Letter Cancellation test for measuring attention, learning style questionnaire for preferred method of learning, before randomization. The experimental (hands facing each other as introduced by Master Choa Kok Sui) and sham (hands facing opposite) groups practiced hands sensitisation. A semi-structured questionnaire was provided to gather information about biofield sensations and the time it took to experience these sensations between the hands. Results All (N=44) the participants in the experimental group and 13 participants in the sham group reported experiencing biofield sensations. A significant difference was noticed in experiencing magnetic (X2 = 38.247, p ≤ .001), physical sensations of energy (X2 = 12.02, p ≤ .001) and pain (X2 = 62.259, p ≤ .001) among the experimental and sham group . In the experimental group, the average time taken to first experience magnetic sensation, other biofield sensations and temperature variation was 34.84±12.97seconds, 40.28±20.96 seconds and 42.50±19.79 seconds, respectively. Minimum time taken to first experience biofield sensation was 5 seconds and lasted up to study duration of 120 seconds. There was no correlation found between reaction time, sustained attention, and the time needed to experience biofield sensations. Conclusions This study highlights importance of Master Choa Kok Sui hand sensitization in controlled setting revealing differences in experiences of various biofield sensations, showing valuable time-related insights and variability of sensation based on preferred learning.

Yield analysis and corn earworm feeding in Bt and non-Bt corn hybrids across diverse locations.

Corn, Zea mays L. (Poales: Poaceae), growers in the US Cotton Belt are required to plant 20% of total corn acres to non-Bt hybrids for resistance management (non-Bt refuge). Most growers do not meet this requirement, in part, because they perceive non-Bt hybrids to yield less than Bt hybrids. We planted multiple non-Bt and Bt hybrids from a single company in small-plot replicated trials at a single location from 2019 to 2023, as well as in small-plot replicated trials at multiple locations during 2022 and 2023. In the single location, we measured kernel injury from corn earworm, Helicoverpa zea Boddie (Lepidoptera: Noctuidae), and we recorded yield at all locations. In the single location trial, yields only separated among hybrids in 3 out of 5 years. In the multiple location trial, yields were variable between both years. We found that Bt hybrids tended to yield higher than non-Bt hybrids overall, but this was influenced by the inclusion of non-Bt hybrids that had a lower overall genetic yield potential in the environments we tested them in. In both tests, when hybrids were analyzed during each year, both Bt and non-Bt hybrids were among the statistically highest yielders. Our study demonstrates the importance of comparing multiple Bt and non-Bt hybrids to draw yield comparisons. This highlights the need for corn seed company breeders to put effort into improving yield for non-Bt hybrids. Hopefully this effort will translate into increased planting of non-Bt refuge corn for growers in the US Cotton Belt.

Testing the response suppression mechanism of working memory.

Many working memory (WM) paradigms involve recalling multiple items from the same memory set. Participants rarely repeat items they have already recalled, avoiding repetition errors. To prevent these errors, WM models incorporate a response suppression mechanism that removes recalled items from the set of response options. Despite its importance for our understanding of WM, response suppression has received limited direct testing. To address this gap, we used computational models implementing two hypothetical mechanisms of response suppression to derive predictions and tested these predictions experimentally. Participants were asked to recall the same items multiple times during a single trial. If already recalled items are removed from the response set to prevent repetition errors, memory performance should be impaired when the same item is tested again. Contrary to this, we found that memory performance was unimpaired when the same item was tested a second time, and even displayed a recall advantage. Therefore, this study demonstrates the implausibility of response suppression to account for how people avoid repetition errors. We discuss alternative explanations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Hyperbaric Oxygen Post Established Stroke.

Hyperbaric oxygen therapy (HBOT) has been reported to improve neurological function in the chronic phase of stroke in a single trial having significant limitations, including a lack of a sham control. We conducted a single-center, parallel-group, randomized trial to determine the effectiveness of HBOT compared with a sham control in adults who were 6 to 36 months post-ischemic stroke.The treatment group received 40 sessions of HBOT at the Vancouver General Hospital Hyperbaric Unit. The control group received 40 sessions of sham treatment designed to replicate an HBOT experience. Due to recruitment challenges and timeline/feasibility tracking by the research team, the control arm was altered after 20 months to a waitlist in the hope of increasing participation. In the second phase, participants were randomized to receive HBOT immediately or following an eight-week observation period. The primary outcome was the post-treatment Stroke Impact Scale-16 (SIS-16). Secondary outcomes included the National Institute of Health Stroke Scale, Berg Balance Test, Digit Symbol Substitution Test, 5-Metre Walk Test, 6-Minute Walk Test, Grip Strength, Montreal Cognitive Assessment, Box/Block Test, and Center for Epidemiological Studies - Depressionand Short Form-36. Based on detecting a clinically important between-group difference of 10 on the SIS-16 score, our target sample size was 68 participants per arm. Results: From January 5, 2016 to October 9, 2018, 34 participants were enrolled in the trial, 27 during the first phase and seven in the second phase.The study was stopped after 36 months, and prior to meeting the sample size target, due to low recruitment.At the end of treatment, the difference in the SIS-16 between groups was 5.5 (95% CI: 1.3 to 9.7, p = 0.01) in favor of the sham group. Our results exclude a clinically important benefit of HBOT on the primary outcome of the SIS-16.Thesefindings do not support the use of HBOT in chronic stroke survivors.

KANSURVIVE: Testing a telementoring model for improving cancer survivorship care in rural practice.

e13791 Background: Cancer survivors require long-term, coordinated care to address the physical, emotional, and psychosocial effects of cancer and its treatment. KanSurvive, a single arm feasibility trial, evaluated the effectiveness of the KanSurvive ECHO intervention combined with practice facilitation (PF) to promote better adoption of evidence-based practice (EBP) survivorship care guidelines for breast, colorectal, lung, and prostate cancer among rural survivors. Methods: Fifteen primary care clinics in Kansas (80% in RUCA codes 4-10), including 62 healthcare professionals, were invited to participate in four, 1-hour Project ECHO telementoring program held in 2021. Real-time videoconferencing sessions covered EBP survivorship guidelines for breast, colorectal, lung, and prostate cancer. Clinics used brief plan-do-study-act cycles with PF supporting implementation of the quality improvement process. Utilizing the National Quality Forum framework, a performance indicator booklet with established measures in preventive health and cancer survivorship was developed as a data collection and quality improvement resource. Performance indicators included EBP screening actions related to cancer surveillance, lifestyle factors, distress, evidence of a review of family history of cancer, and the patient’s cancer diagnosis documented in the EHR. Results: Three clinics (7 = healthcare professionals) withdrew from the project citing competing demands and a provider leaving the practice. The COVID-19 pandemic delayed project initiation and prevented clinic visits. Recruitment and study procedures were implemented remotely. Clinic staff identified 138 cancer survivors (M = 13, IQR [6-16] per practice) seen in the year pre-intervention, and 129 survivors in the year prior to post-intervention. Pre-intervention, overall tumor surveillance was 91%, but lung cancer surveillance was lower than other tumor types at 70%. Other than surveillance, measures of baseline performance were similar across tumor types: screening for distress 84%, assessment of BMI 97%, screening for tobacco use 83% and documentation of family history 70%. Post-intervention performance indicators were similar except for documentation of family history which increased to 89% (p &lt; 0.01). Conclusions: Standardized survivorship metrics can facilitate quality assessment as part of an ECHO-based cancer survivorship program. Although there are modest opportunities for improvement, PCPs in this study caring for rural patients perform reasonably well across a variety of cancer survivorship performance metrics comparable to national primary care quality measures. Documented assessment of family history of cancer lags other metrics and improved after participation in the KanSurvive telementoring program.

Long term outcomes in patients with recurrent/metastatic (R/M) salivary gland cancer (SGC) treated with immune checkpoint inhibitors (ICI).

e18063 Background: There is no standard of care systemic therapy in R/M SGC. Regimens containing ICIs are of interest, but overall response rates (ORRs) are low, and median duration of response (mDOR) and long term overall survival (OS) data are limited. We pooled mature data from two clinical trials evaluating the use of ICIs in SGC to evaluate long term outcomes. Methods: We combined the results of two phase I/II, open label, single arm trials utilizing ICIs in R/M SGC. NCT02538510 administered pembrolizumab 200 mg IV q3 weeks and vorinostat 400 mg PO 5 days on/2 days off. NCT03749460 administered nivolumab 3mg/kg IV q2 weeks x 12 doses, followed by 480 mg IV q4 weeks x 8 doses and ipilimumab 1 mg/kg IV q6 weeks x 4 doses with hypofractionated radiotherapy at 1-5 metastatic sites to a total dose of 24Gy/3 fractions over 1 week initiated 2 weeks after immunotherapy. All patients were ≥18 years with R/M disease, evidence of progression within 3 months of study entry, measurable disease per RECIST 1.1, EGOG PS 0-1, and adequate organ function at enrollment. PDL1 expression was not required for participation and prior ICI was not allowed. ORRs were evaluated by RECIST 1.1. OS and progression free survival (PFS) were estimated via the Kaplan-Meier method. Results: 45 patients were enrolled in the two studies from 11/2015-5/2022. The combined median age was 57 (IQR 46, 66). 26 (57.8%) were male; 33 (73.3%) were white and 10 (22.2%) were Asian. 27 (60.0%) had an ECOG PS of 0. Most common histology types were adenoid cystic carcinoma (21, 46.7%), acinic cell carcinoma (5, 11.1%), and salivary duct carcinoma (5, 11.1%). The ORR was 17.8% with all responders having a PR (n=8, histology types: 3 acinic cell, 2 adenoid cystic, 1 adenocarcinoma, 1 salivary duct, 1 lymphoepithelioma-like carcinoma). 20 (44.4%) had SD, with 16 (80.0%) of these responses lasting greater than 6 months. 16 (35.6%) had PD. One patient was not evaluable for RECIST due to rapid disease progression and death. At analysis, median follow up was 29.2 months (IQR 27.1-50.0) among survivors, mDOR was 26.7 months (range 7.1-69.5+), with three patients with ongoing response. Median OS and PFS were 25.4 (95% CI 14, 43.2) and 6.2 months (95% CI 3.9, 15.5) respectively. 23 (51.1%) patients received systemic therapy after trial ICI. Patients received: 4 additional ICI (3 PD-1 monotherapy, 1 ipi/nivo), 5 androgen deprivation therapy, 5 chemotherapy, 9 other treatments (dabrafenib/trametinib, everolimus, fam-trastuzumab deruxtecan, osimertinib, lenvatinib, investigational agents). Conclusions: Although SGC is heterogenous, responses to ICI were observed in multiple subtypes and were durable, similar to observations in other solid tumors. A significant proportion received subsequent lines of therapy post ICI, and exploration of ORR and PFS to next lines of therapy is of interest. Clinical trial information: NCT02538510 and NCT03749460 .

Quality of life (QoL) benefits following 177Lu-DOTATATE therapy in patients (pts) with 68Ga-DOTATATE PET positive primary site agnostic neuroendocrine tumors (NET).

e16291 Background: The QoL experience during the 1st year of follow up for 68Ga-DOTATATE PET positive primary site agnostic pts with progressive metastatic NET enrolled in a prospective single arm clinical trial of 177Lu-DOTATATE therapy (OZM 067) is described here. Methods: Pts with progressive NET, Ki67 Index &lt; 30%, adequate organ function &amp; ECOG £2 were eligible. Only pts demonstrating positive disease (Krenning score 3-4) on 68Ga-DOTATATE PET were eligible to proceed to 177Lu-DOTATATE therapy (4 cycles at 8- to 12- week intervals. Primary outcome was progression free survival (PFS) at 12 mths. QoL (EORTC QLQ 30 and GINET21) at baseline, 6, 12, 18, 24, 30 months were recorded. Summary scores at time point of interest, and their change from baseline were estimated using a mixed model repeated measure, with baseline assessment included in the model as covariate. Data were normalized with a range of 0-100. A positive change score for Global Summary Status, Functioning Domains, and a negative change score for Symptom Scales and Items represent improvement. A ≥5 point change score is used as a threshold for Minimal Clinically Important Difference (MCID). Results: 195 pts were enrolled. 13 pts were 68Ga-DOTATATE PET negative while 5 pts withdrew consent. 177 pts received at least one dose of 177Lu-DOTATATE. All pts enrolled were eligible for a minimum of 12 mths follow up at time of data lock. The primary site was GEPNET in 143 (81%) and non GEPNET in 34 (19%). At 12 mths, the median follow-up was 33 (range 3-71) mths. PFS and OS were 81 (95% CI: 75-86)% and 92 (87-95)% respectively. QoL data at the following timepoints baseline, 6 &amp; 12 (±2) mths were available in 174,128 &amp; 111 pts respectively. The top three symptoms captured in EORTC QLQ 30 was Fatigue (32.5 SD 23.8) , Insomnia (26.7 SD 28.1) and Diarrhea (22.1 SD 29.4). At 12 mths, an improvement in mean score of ≥MCID in Global Health status (GHS) (+5.4), Role Fc Scale (+7,1), Social Fc Scale (+8.7) and multiple symptoms (Fatigue, Pain, Appetite, Constipation, Diarrhea, Financial Difficulties), Sexual fc, Social, Body image (Table 1) were captured. Conclusions: Patients with primary site agnostic 68Ga-DOTATATE PET positive NET experienced improvement in multiple quality of life domains including multiple symptoms post 177Lu-DOTATATE at 12 mths. Sexual fc and body image had the largest improvement. Clinical trial information: NCT02743741 . [Table: see text]

Durvalumab and consolidation SBRT following chemoradiation for stage III non-small cell lung cancer: A single institution pilot study.

e20085 Background: Definitive chemoradiation (CRT) followed by consolidative immunotherapy with durvalumab (IO) demonstrated survival benefit and is now standard of care for Stage III Non-small Cell Lung Cancer (NSCLC). However, local-regional control (LRC) remains a concern with intrathoracic progression representing the most common site of failure. Adding stereotactic body radiotherapy (SBRT) boost may enhance the immunogenicity and antigenicity of tumor cells by regulating cell surface receptors and augmenting T-lymphocyte infiltration into tumor. SBRT boost also allows escalated dose to the primary tumor while minimizing dose to critical structures. Methods: Patients with Stage III NSCLC planned for definitive concurrent CRT with 1 year of consolidative IO were prospectively enrolled on a single institutional pilot trial. IO started 6-8 weeks after completion of CRT. SBRT was delivered between cycle 1 and 2 of IO to the residual, primary tumor (20 Gy in 2 fractions for peripheral, 19.5 Gy in 3 fractions for central tumors). Residual tumors needed to be &lt; 120 cc. Lymph nodes were not boosted. Primary endpoints were grade (gr) ≥3 toxicities (CTCAE V4.03) and progression free survival (PFS). Secondary endpoints were Overall Survival (OS), LRC, and distant metastasis (DM). A sample size of 25 patients was proposed to determine safety and efficacy. Results: Accrual was slower than anticipated, and the study closed with 11 patients enrolled over 54 months. Slow accrual was due to a low rate of eligibility based on post CRT clinical status and SBRT target limitations. 1 patient withdrew consent before receiving treatment leaving 10 evaluable patients. Median age was 73 years and median CRT dose was 60 Gy (range 60-66 Gy). 6/10 of patient were adenocarcinoma. 5/10 pts had central tumor location. Median follow-up for evaluable patients is 2.2 years. OS was 90%, 70%, and 70% at 1-year, 2-years, and 3 years, respectively. PFS was 90%, 47%, and 47% at 1 year, 2 years, and 3 years, respectively. LRC was 100%, 83%, and 63% at 1 year, 2 years, and 3 years, respectively. Rates of DM were 0%, 12%, and 34% at 1 year, 2 years, and 3 years, respectively. 1 patient developed gr 3 pneumonitis requiring discontinuation of IO. 1 additional patient developed gr 2 pneumonitis requiring a brief pause in IO therapy and resumed IO without any further complications. One patient developed gr 5 myocarditis 29 days after the first dose of IO and 18 days after SBRT, on investigation deemed to be myocarditis secondary to IO. There was no other gr 3 toxicity attributable to IO or SBRT. Conclusions: The addition of SBRT to consolidative IO in stage III NSCLC patients treated with CRT was feasible. The single gr 5 toxicity was attributed to IO. SBRT boost demonstrated encouraging efficacy and manageable toxicity and merits further study. Our data adds to the growing evidence of harnessing tumor immunogenicity in enhancing IO responses. Clinical trial information: NCT03589547 .

Immunogenicity of an AI-designed personalized neoantigen vaccine, EVX-01, in combination with anti-PD-1 therapy in patients with metastatic melanoma.

9561 Background: Personalized vaccines, targeting mutation-derived neoantigens (neoAg), represent a promising frontier in cancer immunotherapy. Here, we characterize the vaccine-induced immune response in seven melanoma patients treated with the AI-generated personalized cancer vaccine, EVX-01, in the ongoing single arm multicenter trial (NCT05309421). Data from an additional five patients will be available at the time of presentation. Methods: Tumor-specific neoAgs were identified and selected using the proprietary vaccine target discovery AI-Immunology platform based on tumor DNA- and RNA-sequencing data. The top-ranked neoAgs for each patient were manufactured as synthetic long peptides and formulated with an adjuvant, creating the personalized cancer vaccine, EVX-01, tailored to the individual tumor and immune system characteristics. Patients initiated anti-PD1 therapy (Pembrolizumab) 12 weeks prior to EVX-01 administration. Each patient received six priming doses of EVX-01 administered bi-weekly and will be followed by four booster immunizations at later timepoints. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples collected at different timepoints to evaluate the effect of anti-PD1 therapy, EVX-01 priming immunizations and EVX-01 booster immunizations on T-cell immunogenicity. NeoAg-specific T-cell responses were evaluated by IFN-γ ELISpot assay and intracellular cytokine staining after T cell in vitro expansion with vaccine neoAgs. Results: Immunogenicity analysis of PBMC samples from seven patients demonstrated that EVX-01 induced neoAg-specific immune responses in all patients after the priming phase. The effect of booster immunizations on neoAg-specific T-cell responses was analyzed in the patients who had reached these late visits of the study, and it demonstrated a clear trend towards increased immune responses after the first booster dose. The observed responses were mediated by both CD4+ and CD8+ neoAg-specific T-cells. Investigations of the response induced by the individual vaccine neoAgs revealed that the majority of the EVX-01 neoAgs triggered a specific T-cell response, affirming the ability of the AI-Immunology™ platform to precisely select effective vaccine targets. Data from an additional five patients will be available at the time of presentation. Importantly EVX-01 was safe and well-tolerated, with only grade 1 and 2 ADRs related to EVX-01 even after boosting. The combination of EVX-01 and anti-PD1 also appeared safe and well tolerated. Conclusions: EVX-01 induced neoAg-specific immune responses in all analyzed patients and a broad response against the neoAgs. These results further validate the precision and predictive power of our proprietary vaccine target discovery AI-Immunology platform. The combination of EVX-01 and anti-PD1 was safe and well tolerated. Clinical trial information: NCT05309421 .

Patient-reported experience with an immunotherapy telehealth platform.

1637 Background: The Making Telehealth Delivery of Cancer Care at Home Effective and Safe for Immunotherapy (MATCHES-IO) intervention seeks to improve the efficiency and patient experience for those treated with single agent pembrolizumab. Because pembrolizumab is administered as an outpatient infusion every 3-weeks, patients require up to 18 clinic visits per year to receive treatment, which is arduous. During the COVID-19 pandemic, the FDA granted accelerated approval for an extended interval dosing administered every 6 weeks, but despite this approval every 3-week dosing remains the standard (65% of prescriptions) as clinicians perceive this schedule enables them to identify and manage toxicity early. Telehealth may be the impetus to change the standard to the more convenient 6-week in person schedule, but evidence is needed. Methods: We conducted a single arm pragmatic trial to evaluate the efficiency and patient experience of a telehealth immunotherapy platform (MATCHES-IO) in patients with non-small cell lung, genitourinary, or melanoma cancers receiving single agent pembrolizumab. MATCHES-IO evaluates whether in-person visits for pembrolizumab therapy q6wk (rather than q3wk), with interim telehealth toxicity checks between in-person treatments, is more efficient and enhances patient experience relative to the standard q3wk infusion visits. The components of the platform include clinician-patient virtual visits, labs at home, biometric devices at home for vital sign monitoring, and electronic patient-reported outcomes to monitor for common IO-related toxicities. Patient experience was assessed after each MATCHES-IO televisit for up to two televisits. We measured experience with a patient experience survey that included the net promoter score, of how likely are they to recommend this intervention to similar patients (scale 0-10, higher score is desirable). A score of 9 or greater is considered excellent. Results: Between July 2023 and February 2024, 27 patients were enrolled, median age 68 (range 45–85), 74% white, 11% black, 11% Asian, and 41% female. Cancer types included thoracic (59% of patients), genitourinary (33%), and melanoma (7%). 19 patients (70.4%) have completed a MATCHES-IO televisit and completed the patient experience survey. The median net promoter score was 9 (range 2-10). 94% patients perceived a benefit to the MATCH-IO televisit including saved time (83% of respondents), patient convenience (83%), convenience for caregiver/family (44%), saved money (44%), and better monitoring of cancer and treatment (39%). 78% of patients found the at home visit less stressful than the in-person visit. Conclusions: Patients endorsed an enhanced experience with an immunotherapy telehealth platform for extended dosing of pembrolizumab. Further follow-up is needed to confirm these experience findings and determine whether this platform improved efficiency through fewer in-person visits.

A phase II trial of reirradiation combined with pembrolizumab in patients with locoregional inoperable recurrence or second primary squamous cell carcinoma of the head and neck (HNSCC).

6049 Background: Better outcomes are needed for patients (pts) with locoregional inoperable recurrence or second primary HNSCC after prior radiation therapy. Methods: We conducted a phase II single arm trial of hyperfractionated reirradiation (ReRT, 1.2 Gy BID for total 60Gy to gross disease + margin without elective nodal radiation) plus pembrolizumab (P) (200mg q3 weeks starting day 1 of ReRT). P was continued until confirmed CR or if no CR, until disease progression or up to 24 months. All pts underwent a 3 month post ReRT PET/CT and subsequently CT neck/chest after every 3rd cycle of P. Pts included had: Locoregional recurrence or second primary HNSCC (excluding skin or salivary), were unresectable or not willing to undergo resection, one RT course completed at least 6 months prior, with &gt;50% tumor volume treated at doses &gt;45Gy, ECOG PS 0-1, a target lesion by RECIST, no distant metastasis, and no prior anti-PD-1/PD-L1. Primary endpoint was PFS, and the hypothesis was that the median PFS would increase from the historical control of 8 months (mo) to 12 mo, α=0.05, power 78%, n=48. Secondary endpoints: ORR by RECIST, OS, toxicity, QOL (EORTC). The Kaplan-Meier method was used to estimate PFS and OS. Results: In the 48 evaluable pts, median age was 65.5 (range 44-79), 62.5% male. Primary site: hypopharynx (8.3%), larynx (6.3%), nasopharynx (10.4%), oral cavity (43.7%), oropharynx (31.3%, one HPV+ pt). Median doses of P was 8, median RT dose was 60 Gy and 20.8% received proton RT, remainder IMRT. Median follow up was 49.1 months. The median PFS was 8.3 mo (95%CI 5.5-10.3), and median OS was 13.8 mo (95% CI 9.5-21.8). 1 and 3-year PFS were 28.9% and 22.3% respectively, and for OS 54.2% and 25.7%, respectively. 42 pts were evaluable for response and the ORR was 54.8% (33.3% CR, 21.4%PR), 21.4% SD, 23.8% PD. In an exploratory analysis, the median PFS was 13.8 mo (95% CI 9.1-NR) and the median OS was 57.8 mo (19.6-NR) in patients that had a response (CR/PR, n=23), with a 1 and 3-year PFS of 51.8% and 42.4%, respectively, and for OS 78.3% and 51.7%, respectively. All patients had at least one treatment related AE (TRAE), defined as possibly, probable, or definitely related to treatment. 39% of pts had a G3 TRAE and the most common ones were: aspiration, dehydration, anemia, dysphagia, dyspnea. 4 patients had a G5 TRAE (found down deceased, epistaxis, aspiration pneumonia, iRAE pneumonitis). Conclusions: Our prospective trial uniquely evaluated ReRT plus pembrolizumab in patients with locoregional recurrence/second primary HNSCC that did not undergo salvage surgery. The primary endpoint of PFS was not improved compared to historical control. PD-L1 biomarker analysis is ongoing and will be reported subsequently. Clinical trial information: NCT02289209 .

A pilot study of early PET and biomarker dynamics in patients with stage 2 and 3 triple negative breast cancer treated with neoadjuvant response-adapted chemotherapy with pembrolizumab (NeoADAPT).

TPS624 Background: In patients with triple negative breast cancer (TNBC) the addition of pembrolizumab to neoadjuvant chemotherapy has improved pathologic complete response rates (pCR) and 5-year event free survival (EFS). Patients with TNBC who achieve a pCR have a significantly lower risk of recurrence compared to those with residual disease (RD). However, pCR can only be assessed at the time of surgery after completion of 6 months of intensive chemo-immunotherapy, associated with up to 77% high-grade treatment-related toxicity. Identifying pCR early on is imperative in developing optimized and individualized treatments, however, there are no predictive biomarkers. Studies in HER2-positive breast cancer have shown that early fluorodeoxyglucose positron emission tomography (FDG-PET) changes soon after initiation of neoadjuvant treatment can help predict the pathological outcomes at the time of surgery and also the risk of recurrence. Emerging data also support that clearance of circulating tumor DNA (ctDNA) during neoadjuvant treatment may be associated with higher rates of pCR. We thus designed a study to determine the association of early FDG-PET changes and ctDNA clearance with pCR in early-stage TNBC. Methods: NeoADAPT is a phase 2, open label, single center clinical trial including adult patients with previously untreated clinical stage 2 or 3 TNBC. Participants will receive 4 cycles of neoadjuvant paclitaxel/carboplatin with pembrolizumab (TC/pembro), per standard-of-care (SOC). An FDG-PET will be performed at baseline and after 1 cycle. A breast MRI will be performed at baseline and after completion of 4 cycles of treatment. Patients with a complete clinical response (cCR) will proceed to surgery and will forgo more neoadjuvant treatment. Patients with clinical RD on MRI will complete SOC neoadjuvant therapy with 4 cycles of doxorubicin/cyclophosphamide (AC) with pembro prior to surgery. If RD is identified after surgery, adjuvant therapy will be determined by the treating oncologist, which may include pembro with AC (if not given prior), capecitabine, etc. The primary objective is to evaluate if lack of decrease in maximum FDG-PET standard uptake value of lean body mass (SULmax) by less than 40% after 1 cycle of neoadjuvant treatment correlates with RD at the time of surgery (i.e. determining the negative predictive value of FDG-PET). Additional key endpoints include ctDNA clearance, evaluation of pCR and cCR rates in the treatment population and EFS. Distributions of percent reduction in SULmax will be compared between pCR and no-pCR groups using the Wilcoxon rank sum test. Receiver operating characteristic (ROC) curve analysis will be performed to estimate the ability of FDG-PET SULmax reduction and cCR by MRI in predicting pCR at surgery. Clinical trial information: NCT06245889 .

Clinical activity and safety of naptumomab estafenatox (NAP) and docetaxel in patients (pts) with checkpoint inhibitor (CPI) –pretreated advanced/metastatic non-small cell lung cancer (NSCLC): Preliminary results of a P2 trial.

8615 Background: NAP is a chimeric protein composed of a superantigen (SAg) and a Fab targeting common tumor antigen 5T4, which is highly expressed in NSCLC. Its therapeutic effect is associated with activation, expansion, and tumor infiltration of SAg-binding specific T cells. Docetaxel is important therapeutic component in the treatment of advanced-stage NSCLC and SOC after failure of chemo-immunotherapy. We present initial results from this open label single arm trial, with advanced/metastatic NSCLC pts previously treated with at most 2 prior systemic therapies, including platinum-based chemotherapy and CPI, were treated with NAP and docetaxel. Methods: Patients were treated with NAP at 10 mcg/kg and docetaxel at a standard dose (75 mg/m2) in 21 day cycles for up to 2 years. If docetaxel was discontinued, NAP could be continued as monotherapy in 28 day cycles. Obinutuzumab pretreatment prior to cycle 1 used to inhibit anti-drug antibodies (ADAs) to NAP. Primary objective was overall response rate (ORR) and duration of response (DOR) based on institutional iRECIST review. Secondary objectives included safety, progression free survival (PFS) and overall survival (OS). Results: The trial enrolled 38 pts, 36 received NAP, 32 had post baseline imaging and were evaluable for response. Median age 66 yrs (33-85), 55% male, ECOG 0 in 26% and 1 in 74%. Eight pts (21%) had CNS involvement at baseline but brain MRI was not initially required, but implemented later in the trial. All pts received platinum-based chemotherapy and CPI, with a median of 2 (1-4) prior regimens. Nine pts (24%) received 2 CPI containing regimens. NAP safety was acceptable and consisted of mostly grade 1-2 infusion related reactions, were generally easily manageable and rapidly reversable that were in line with previous reports. Pts received median of 4 combination cycles and 14 pts (39%) continued NAP as monotherapy. NAP treatment was discontinued due to toxicities in 2 pts (5%). Five pts had PR, 2 of them unconfirmed, ORR 16%. Two pts had prolonged responses: one lasted for 22 m and the second had CR in target lesions lasted for 24 m with progression in brain treated with radiation, which did not compromise pts systemic response. One pt had initial pseudo-progression in target lesions with a subsequent PR, suggesting a possible immune response. Mean response duration was 7.3 m (1.3 - 20.8). Mean PFS was 4.6 m, 18 pts (56%) had SD, disease-control rate (DCR) was 72%, with mean duration of 5.3 m. Median OS was 8 months with 11 pts (34%) still alive at database lock and 3 pts receiving NAP under individual expanded access protocol. Conclusions: These preliminary results of NAP + docetaxel show potential evidence of activity with acceptable safety in heavily pre-treated NSCLC pts. Further trials of NAP in combination, including CPIs are planned. Clinical trial information: NCT04880863 .