Despite curative-intent treatment, most patients with locally advanced esophageal cancer will experience disease recurrence or locoregional progression, highlighting the need for new therapies. Current guidelines recommend definitive chemoradiotherapy in patients ineligible for surgical resection, but survival outcomes are poor. Pembrolizumab is well tolerated and provides promising antitumor activity in patients with previously treated, advanced, unresectable esophageal/esophagogastric junction cancer. Combining pembrolizumab with chemoradiotherapy may further improve outcomes in the first-line setting. Here, we describe the design and rationale for the double-blind, Phase III, placebo-controlled, randomized KEYNOTE-975 trial investigating pembrolizumab in combination with definitive chemoradiotherapy as first-line treatment in patients with locally advanced, unresectable esophageal/gastroesophageal junction cancer. Overall survival and event-free survival are the dual primary end points. Clinical trial registration: NCT04210115 (ClinicalTrials.gov)

Context. Optimal advance care planning allows patients to articulate their values as a touchstone for medical decision making. Ideally, this occurs when patients are clinically stable, and with opportunities for iteration as the clinical situation unfolds. Objectives. Testing feasibility and acceptability in busy outpatient oncology clinics of a novel program of systematic, oncology nurse-led values discussions with all new cancer patients. Methods. Within an institutional initiative integrating primary and specialist palliative care from diagnosis for all cancer patients, oncology nurses were trained to use specific questions and an empathic communication framework to discuss health-related values during outpatient clinic visits. Nurses summarized discussions on a template for patient verification, oncologist review, and electronic medical record documentation. Summaries were reviewed with the patient at least quarterly. Feasibility and acceptability were evaluated in three clinics for patients with hematologic or gastrointestinal malignancies. Results. Oncology nurses conducted 177 total discussions with 67 newly diagnosed cancer patients (17 with hematologic and 50 with gastrointestinal malignancies) over two years. No patient declined participation. Discussions averaged eight minutes, and all patients verified values summaries. Clinic patient volume was maintained. Of 31 patients surveyed, 30 (97%) reported feeling comfortable with the process, considered it helpful, and would recommend it to others. Clinicians strongly endorsed the values discussion process. Conclusion. Nurse-led discussions of patient values soon after diagnosis are feasible and acceptable in busy oncology clinics. Further research will evaluate the impact of this novel approach on additional patient-oriented outcomes after broader dissemination of this initiative throughout our institution.

Background: Prior work to integrate early palliative care in oncology has focused on patients with advanced cancer and primarily on palliative care consultation. We developed this outpatient clinic initiative for newly diagnosed patients at any stage, emphasizing primary (nonspecialist) palliative care by oncology teams, with enhanced access to palliative care specialists. Methods: We piloted the project in two medical oncology specialty clinics (for patients with myelodysplastic syndrome and GI cancer, respectively) to establish feasibility. On a visit-based schedule, patients systematically reported symptoms, information/decision-making preferences, and illness understanding. They also participated in discussions of their core values with their oncology nurse. Oncology teams were first responders to palliative care needs, whereas specialists were available for clinician support and direct patient consultation. Results: All 58 eligible patients were enrolled. In both clinics, patient self-reports documented a heavy symptom burden. Information/decision-making preferences and illness understanding levels varied across patients. Patients prepared new advance directives. Oncology nurses documented discussions of core values. Requests for palliative care consultation decreased over time as oncology teams embraced their primary palliative care role with coaching from the specialists. Clinic workflow and patient volume were maintained. Conclusion: Our pilot experience suggests that in outpatient oncology clinics, a structured, scheduled, and systematic approach is feasible to deliver palliative care to newly diagnosed patients with cancer at any stage and throughout their illness trajectory. This novel approach identified important, actionable palliative care needs, relying primarily on oncology teams to respond to these needs, while enhancing access to palliative care specialist input. Expansion to additional clinics will allow evaluation of scalability and generalizability, along with measurement of a broader range of important outcomes.

BackgroundImmune checkpoint inhibitors (ICI) are standard-of-care in the treatment of several types of cancer; however, an unmet medical need exists for early-line combination therapies that are able to provide higher response rates, more durable responses, and manageable long-term safety. Lifileucel (LN-144) and LN-145, adoptive cell therapies using tumor-infiltrating lymphocytes (TIL), have demonstrated encouraging efficacy with acceptable safety in patients with advanced cancer that has failed ICI.1–2 To improve efficacy and safety of early-line treatment options, we explored a combination of TIL and pembrolizumab in patients with ICI-naïve melanoma, head and neck squamous cell carcinoma (HNSCC), and cervical cancer.MethodsIOV-COM-202 (NCT03645928) and C-145-04 (NCT03108495) are ongoing Phase 2 multicenter, multicohort, prospective, open-label studies evaluating TIL cell therapy in ICI-naïve patients with solid tumors. We report efficacy and safety from IOV-COM-202 (Cohort 1A: lifileucel and pembrolizumab in patients with unresectable or metastatic melanoma; Cohort 2A: LN-145 and pembrolizumab in patients with advanced, recurrent, or metastatic HNSCC) and C-145-04 (Cohort 3: LN-145 and pembrolizumab in patients with stage 4b, persistent or recurrent cervical cancer who have not received prior systemic therapy). Eligibility across cohorts included ECOG PS ≤1, ≥1 resectable lesion (diameter ≥1.5 cm post-resection) for TIL manufacturing, and ≥1 measurable lesion for response assessment (by investigator per RECIST v1.1). Lifileucel and LN-145 are cryopreserved TIL infusion products generated at central GMP facilities in a 22-day process. Treatment included tumor resection for TIL manufacturing, followed by 1 dose of pembrolizumab, nonmyeloablative lymphodepletion (cyclophosphamide and fludarabine), TIL infusion, ≤6 interleukin-2 doses (600,000 IU/kg IV), and continued pembrolizumab for ≤24 months.ResultsAs of 09July2021, 32 patients received TIL and pembrolizumab (full-analysis set [FAS]; table 1). Across all cohorts, the objective response rate (ORR) in the FAS was 56.3% (Cohort 1A [melanoma], 87.5%; Cohort 2A [HNSCC], 42.9%; Cohort 3 [cervical], 50.0%; figure 1). Among confirmed responders (n=17), 10 responses (58.8%) were ongoing at data cutoff, with a median study follow-up of 9.7 months. The treatment-emergent adverse-event (TEAE) profile was consistent with the underlying diseases and known profiles of pembrolizumab, nonmyeloablative lymphodepletion, and interleukin-2. The most common (≥30%) Grade ≥3 TEAEs were thrombocytopenia (53.1%), anemia (50.0%), neutropenia (46.9%), and febrile neutropenia (43.8%).ConclusionsThe observed efficacy, including ORR and CR rate, and acceptable safety profile are encouraging and warrant continued investigation of the combination of TIL and pembrolizumab in early-line treatment of patients with advanced cancer. Enrollment is ongoing; updated data will be presented.AcknowledgementsThis study and analysis were funded by Iovance Biotherapeutics, Inc. (San Carlos, CA, USA). Writing support was provided by Amanda Kelly (Iovance); graphics support was provided by Cognition Studio (Seattle, WA, USA).Trial RegistrationNCT03645928 and NCT03108495ReferencesSarnaik AA, et al. J Clin Oncol 2021; doi: 10.1200/JCO.21.00612.Jazaeri AA, et al. J Clin Oncol 2019;37 (suppl; abstract 182).Jimeno A, et al. J Immunother Cancer 2020;8 (suppl; abstract 353).Ethics ApprovalThe IOV-COM-202 study was approved by Advarra Institutional Review Board, approval number Pro00035064; the C-145-04 was approved by WIRB Copernicus Group, approval number 7-1425772-1. All study participants provided written consent via signature of the IRB-approved informed consent form.Abstract 492 Table 1Baseline demographic and clinical characteristics and efficacyAbstract 492 Figure 1Best percentage change from baseline in target lesion sum of diameters for efficacy-evaluable set*