Price, Katharine A.

TPS6111 Background: Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has surpassed cervical cancer as the most common HPV-related cancer in the US, with the majority being caused by HPV16. Persistent expression of HPV16 oncoproteins E6 and E7 by host genome may promote HNSCC. HPV16-positive HNSCC may be associated with poor clinical outcomes in the recurrent/metastatic (R/M) setting. PDS0101 (Versamune HPV) is an HPV16-immunotherapy that generates a potent, targeted T cell attack against HPV16 E6 & E7. In a Phase 2 study, PDS0101 plus pembrolizumab has shown encouraging safety and survival benefit in patients with HPV16-positive R/M HNSCC. (Weiss J et al. ESMO 2024. Poster 879P. NCT04260126). Methods: VERSATILE-003 is a global Phase 3, randomized, controlled, open-label study evaluating PDS0101 plus pembrolizumab vs. pembrolizumab in patients with HPV16-positive R/M HNSCC with PD-L1 positive disease (CPS ≥1). Key eligibility criteria include age ≥18-years-old, histologically- or cytologically-confirmed diagnosis of R/M HNSCC with primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx and no prior systemic anticancer treatment in the R/M setting, HPV16 tumor positivity (centrally tested), PD-L1 positivity defined as CPS ≥ 1 using FDA-approved PD-L1 IHC 22C3 pharmDx kit, and measurable disease based on RECIST 1.1 confirmed by blinded independent central review (BICR). Patients will be randomized 2:1 to receive pembrolizumab 200 mg IV Q3W with PDS0101 1 mL SC administered concurrently during Cycles 1, 2, 3, 4, and 12 (investigational arm), or pembrolizumab 200 mg IV Q3W alone (control arm). The primary objective is to compare overall survival (OS) between the investigational and control arms. Secondary objectives include objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and progression-free survival (PFS) using RECIST 1.1 and assessed by BICR. Exploratory objectives include tumor response assessed by investigator and by irRECIST, PFS2, quality of life as assessed by EQ-5D, QLQ-C30, and QLQ H&N35, and assessment of ctHPVDNA. Updated enrollment data will be provided. Clinical trial information: NCT06790966 .

e13718 Background: Oncology has evolved in the cyber era of medicine. The 21 st Century Cures Act mandated patient access to medical data (tests, provider notes) via patient portals connected to EHRs in order to facilitate patient engagement. Furthermore, the COVID-19 pandemic rapidly transformed patients’ interactions with portals by increasing reliance on telehealth and portal messaging. This shift has been well-documented in primary care, and emerging research suggests similar trends in oncology. More information is needed regarding how this has evolved post-pandemic. We present single academic institution real-world data (RWD) describing ongoing changes in patient messages and telephone calls in oncology. Methods: We quantified the changes (2019-2024) within oncology at Mayo Clinic Rochester campus including all care team, provider, nursing, and pharmacist visits, patient portal medical advice requests, patient calls, and messages sent to patients per year using Epic's SlicerDicer™ tool. Results: Patient visits/year dipped (-0.2%) from 2019 to 2020, but increased steadily from 2021 forward (Table 1). Patient portal advice requests increased significantly faster (Table 1); from 2019 to 2024, visits /year increased by 40%, while the number of advice requests increased by 131%. Patient calls/year increased more modestly (64%), while the number of messages sent to patients increased by 163% over this time. Conclusions: The transparency allowed by the Cures Act coupled with the impact of the pandemic has empowered patients to engage in their oncology care more proactively through the EHR. Patient-initiated portal messaging is increasing, with messages sent to patients from the oncology department similarly rising. Patient call volumes are also growing despite EHR messaging. Further research is necessary to better understand patterns of EHR use in oncology and explore ways to reduce clinician burnout that may arise from responding to this increased communication volume, as well as to understand the impact on patient satisfaction and outcomes. Changes in patient volume compared to patient calls and EHR messaging over time. Year Total Patient Visits Change in Patient Visits from Prior Year (%) Total Patient Medical Advice Messages Change in Patient Medical Advice Message Volume from Prior Year (%) Total Patient Calls Change in Patient Call Volume from Prior Year (%) Messages Sent to Patients Change in Patient Messages Sent to Patients from Prior Year (%) 2019 62,440 n/a 173,177 n/a 195,143 n/a 99,974 n/a 2020 61,959 -0.7 218,976 +26.5 240,833 +23.4 135,044 +35.1 2021 70,950 +14.5 276,561 +26.3 267,395 +11.0 165,293 +22.4 2022 74,961 +5.7 325,580 +17.7 263,732 -1.4 206,043 +24.7 2023 80,672 +7.6 349,756 +7.4 274,446 +4.0 214,257 +4.0 2024 87,605 +8.6 399,740 +14.3 319,963 +16.6 263,271 +22.9

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses, as well as occult primary cancer, salivary gland cancer, and mucosal melanoma (MM). The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding management of nasopharynx cancer and ongoing research in this area.

Background: Underrepresented minority (URM) patients enroll in cancer clinical trials at low rates. We studied the perspectives of health care professionals to better understand the challenges and potential facilitators of recruiting URM patients into clinical trials. Methods: A purposeful sampling approach was utilized to recruit health care professionals and clinical research staff who recruited and cared for URM patients in a therapeutic cancer clinical trial at any Mayo Clinic site, from July 2018 through October 2021.Data were gathered using a semistructured qualitative interviews. Participants were interviewed about the challenges of recruiting URM patients into cancer clinical trials and possible strategies for improving URM patient enrollment. Data were analyzed using a thematic analysis. Results: Of the key themes that emerged from participant interviews ( n = 28), perceived barriers to recruiting URM patients into clinical trials included lack of workforce diversity, underutilization of patient navigators, ineffective community outreach and patient recruitment, restricted access to diverse patient populations, and restrictive clinical trial eligibility criteria. Other barriers reported were lack of insurance and access to care and transportation, low socioeconomic status, and mistrust of health care and research. Strategies suggested for improving the recruitment of URM patients into clinical trials included: diversifying and adding research staff, increasing and improving community outreach and advocacy, partnering with clinics closer to patients, increasing monetary and logistical support for patient participation, creating opportunities that build and enhance trust, and systematically examining and modifying clinical trial eligibility criteria. Conclusions: Our findings reveal barriers that have limited URM patient inclusion in cancer clinical trials and highlight strategies to overcoming these barriers.

Background Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients. There is a critical clinical need to identify patients who benefit from these antiprogrammed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors. Methods Here, we report findings from a multicenter observational study, PREDicting immunotherapy efficacy from Analysis of Pre-treatment Tumor biopsies (PREDAPT), conducted across 17 US healthcare systems. PREDAPT aimed to validate OncoPrism-HNSCC, a clinical biomarker assay predictive of disease control in patients with recurrent or metastatic HNSCC treated with anti-PD-1 immune checkpoint inhibitors as a single agent (monotherapy) and in combination with chemotherapy (chemo-immunotherapy). The test used RNA-sequencing data and machine learning models to score each patient and place them into groups of low, medium, or high. Results The OncoPrism-HNSCC prediction significantly correlated with disease control in both the monotherapy cohort (n=62, p=0.004) and the chemo-immunotherapy cohort (n=50, p=0.01). OncoPrism-HNSCC also significantly predicted progression-free survival in both cohorts (p=0.015 and p=0.037, respectively). OncoPrism-HNSCC had more than threefold higher specificity than programmed death-ligand 1 combined positive score and nearly fourfold higher sensitivity than tumor mutational burden for predicting disease control. Conclusions Here, we demonstrate the clinical validity of the OncoPrism-HNSCC assay in identifying patients with disease control in response to anti-PD-1 immune checkpoint inhibitors. Trial registration number NCT04510129.

6041 Background: Human papillomavirus (HPV) E6/E7 oncoproteins mediate immune evasion by down-regulating Type 1 interferons, TLR9, MHC Class I/II as well as other mechanisms, resulting in persistent infection and initiation of ̃5% of all cancers globally. Similarly, established cancers evade immune surveillance utilizing parallel mechanisms including the expression of checkpoint proteins. PDS0101 is a molecularly targeted immunotherapeutic based on an enantiospecific cationic lipid nanoparticle platform containing HPV16 neoantigens that exhibits anti-tumor activity with checkpoint inhibitors (CPIs) by upregulating Type I interferons and promoting antigen processing and cross presentation. This allows generation of high levels of polyfunctional HPV16-specific CD8 and CD4 T cells in vivo as well as immune memory. VERSATILE-002 (NCT04260126) is a phase 2 study of the combination of PDS0101 and pembrolizumab in treatment of CPI naïve and refractory patients with recurrent or metastatic HPV16-related HNSCC. Herein, we report preliminary safety and efficacy data for CPI naïve patients at a prespecified interim analysis. Methods: Subjects are treated with pembrolizumab 200mg IV every three weeks plus SC PDS0101 following pembrolizumab on days one of Cycles1-4 and Cycle12; pembrolizumab continues up until 35 cycles, disease progression or intolerance to therapy. Results: Eighteen CPI naïve subjects with confirmed HPV16 tumors and a CPS score > = 1, median age 62 yrs (range 46-71), all male, 17 (94%) of whom were White and 16 (88.9%) not Hispanic or Latino, received at least one cycle of combination therapy. At the time of analysis, 17 (94%) subjects had received > = 4 doses of PDS0101 (median 4, range 1-5) and pembrolizumab (median 7, range 1-14). There were no Grade 3 or greater treatment-related toxicities and no drug discontinuation related to toxicity or immune-related AEs. Clinical activity (CR+PR+SD) was seen in 13 (72.2%) of 18 subjects, with best overall reponse per RECIST1.1 documenting: OR in 7 (38.9%; 2 CR, 5PR); stable disease (SD) in 6 (33.3%) and progressive disease in 3 (16.7%); 2 subjects had missing data. Tumor reduction was seen in 4 of 6 (67%) subjects with SD. Nine-month PFS and OS rates (95% CI) were 52% (22.5, 74.7) and 81% (37.8, 95.5) respectively; median PFS and OS have not been reached. Conclusions: The combination of PDS0101 and pembrolizumab demonstrates an excellent safety profile with preliminary evidence of clinical activity in the majority of CPI naïve patients with HPV-related HNSCC. Clinical trial information: NCT04260126.

Head and neck cancer (HNC) accounted for 4% of all malignancies in 2022 and is often associated with tobacco and alcohol use, but the incidence of human papillomavirus (HPV)–associated HNC has steadily increased in recent decades. Unlike HPV-negative HNC, HPV-positive HNC has a favorable prognosis and survival is significantly better resulting in a large population of HNC survivors. Survivorship for HNC is of the utmost importance as there is a high burden of side effects that impact function and quality of life, and the patients with HPV HNC are living longer with the sequelae of their treatment.

Abstract Background: Much has been published about barriers to research participation for under-represented minority (URM) yet we know little about the experiences, motivations, and decision-making of the URM patients who were successfully treated on clinical trial (CT). The purpose of this study is to draw on the experiences of URM patients as insiders of practical knowledge of CT through photo elicitation to comprehensively understand the current state of recruitment and treatment of URM patients on interventional cancer CTs across the Mayo Clinic enterprise with a short-term goal of informing mechanisms to enrich CT participation and a long-term goal of building a patient-centered cancer practice and clinical trial patient population that is reflective of the diverse communities served by Mayo Clinic. Method: An Appreciative inquiry approach was adapted for this study which acknowledges that existing strengths and everyday experiences of URM patients has the potential to allow a more nuanced view as it pertains to our cancer populations. A total of 138 URM were invited to participate. Using photo elicitation technique, patients were asked to take photographs to portray factors that motivated them and/or facilitated their enrollment, barriers to enrollment and recommendations to improve the process for CT recruitment for other URM. Participant-generated photographs (59) and accompanying 13 interview narratives were analyzed using layered analysis. Results: A total of 13 patients (female =9) participated in the photo interviews. URM detailed their overall experiences around CT participation, motivations for participating in clinical trials; facilitators to clinical trial participation; and opportunities and considerations for increasing minority patients CT participation. Photo analyses provided symbolic representation of patients’ general experiences around CT including celebrating their “new identity”, finding peace in moments of nostalgia, their journey through the trial, lost times and finances and yet finding a new purpose to live through CT participation. Importantly patients described decision making in CT participation as a relational approach. Patients suggested opportunities and considerations for increasing minority patients trial participation, which included minimizing logistical barriers, decentralizing cancer clinical trials, increasing awareness via patient narratives, diversifying research staff, minimizing cost, and being clear on purpose and benefit of the trial. Conclusion: Our study highlights the potential to utilize visual data and narratives from URM in CT recruitment and education programming. It provided valuable insights from the URM community for the URM community on key issues on motivations of CT participation and decision-making in CT participation. Citation Format: Gladys B. Asiedu, Rahma Warsame, Mary O’Shea, Yong-hun Kim, Sara A. Ellingson, Katharine A. Price. Trial participation in pictures: Using photo elicitation to explore minority patients’ experiences on therapeutic cancer clinical trials [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A076.

Background: Cancer distress management is an evidence-based component of comprehensive cancer care. Group-delivered cognitive behavioral therapy for cancer distress (CBT-C) is the first distress treatment associated with replicated survival advantages in randomized clinical trials. Despite research supporting patient satisfaction, improved outcomes, and reduced costs, CBT-C has not been tested sufficiently within billable clinical settings, profoundly reducing patient access to best-evidence care. This study aimed to adapt and implement manualized CBT-C as a billable clinical service. Patients and Methods: A stakeholder-engaged, mixed-methods, hybrid implementation study design was used, and the study was conducted in 3 phases: (1) stakeholder engagement and adaptation of CBT-C delivery, (2) patient and therapist user testing and adaptation of CBT-C content, and (3) implementation of practice-adapted CBT-C as a billable clinical service focused on evaluation of reach, acceptability, and feasibility across stakeholder perspectives. Results: A total of 40 individuals and 7 interdisciplinary group stakeholders collectively identified 7 primary barriers (eg, number of sessions, workflow concerns, patient geographic distance from center) and 9 facilitators (eg, favorable financial model, emergence of oncology champions). CBT-C adaptations made before implementation included expanding eligibility criteria beyond breast cancer, reducing number of sessions to 5 (10 total hours), eliminating and adding content, and revising language and images. During implementation, 252 patients were eligible; 100 (40%) enrolled in CBT-C (99% covered by insurance). The primary reason for declining enrollment was geographic distance. Of enrollees, 60 (60%) consented to research participation (75% women; 92% white). All research participants completed at least 60% of content (6 of 10 hours), with 98% reporting they would recommend CBT-C to family and friends. Conclusions: CBT-C implementation as a billable clinical service was acceptable and feasible across cancer care stakeholder measures. Future research is needed to replicate acceptability and feasibility results in more diverse patient groups, test effectiveness in clinical settings, and reduce barriers to access via remote delivery platforms.