Immunotherapy has shown promise in cancer treatment, but resistance remains a major challenge. Combining therapies that target specific pathways, such as TGF-β signaling, can enhance the effectiveness of immune checkpoint inhibitors (ICIs). Our oncolytic adenovirus (OAd), mHAdLyp.sT, containing a TGF-β decoy to reverse immune resistance to ICI treatment and the LyP-1 peptide to enhance tumor targeting, has been shown to significantly enhance anti-tumor responses and reduced lung metastasis in a 4T1 triple negative breast cancer (TNBC) mouse model when systemically delivered in combination with anti-PD-1 and anti-CTLA-4 antibodies. We also showed previously that mHAdLyp.sT systemically primes an inflamed immune cell phenotype for ICI treatment by both flow cytometry and mass cytometry (CyTOF). In this study, we investigated how the mHAdLyp.sT-ICIs combination affects the expression of key genes in major signaling and immune regulatory pathways by RNA-seq analysis, both in tumors and systemically in the spleen, at the early response stage (day 16) and experiment terminal point (day 25) in the TNBC mouse model. In tumor, both ICIs and the mHAdLyp.sT-ICIs combination treatments significantly induced immune-related genes beneficial for anti-tumor effects compared to the untreated control group at both day 16 and day 25. However, at day 16, while ICI treatment significantly escalated the expression of several proinflammatory cytokines, such as IL-6, IL-10, and IL-11, which are known to potentiate tumor resistance to immunotherapy, mHAdLyp.sT-ICIs combination treatment did not trigger this response. In the spleen, all treatments exhibited slight effects on the immune response at day 16, while at day 25, mHAdLyp.sT-ICIs combination induced a strong response with extensive rescued changes across various crucial signaling pathways in tumor progression and metastasis, including those involved in TGF-β signaling, cell adhesion, migration, angiogenesis, extracellular matrix organization, cell differentiation, gene expression regulation, protein phosphorylation, inflammation, and apoptosis. Notably, mHAdLyp.sT-ICIs combination treatment more effectively inhibited immunosuppressive genes such as Myd88 and Ptgir than ICI alone, confirming that TGF-β inhibition by mHAdLyp.sT enhanced anti-tumor immune responses and helped overcome ICI resistance. We are confident in advancing this new treatment option for TNBC and other metastatic cancers that are projected to be resistant to immunotherapy in a clinical setting. Nguyễn Thị Thanh Nhàn, Beniamin Filimon, Hailie Fowler, Sheetal Ganesan, Xinkun Wang, Bruce Brockstein, Weidong Xu. Transcriptomic analysis ofTGF-β-targeting oncolytic adenovirus and immune checkpoint inhibitor therapy in a triple-negative breast cancer mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 654.

Despite therapeutic advancements, metastatic triple negative breast cancer (TNBC) remains mostly incurable and is a frequent cause of cancer-related deaths. We tested the hypothesis that inhibiting suppressive signals sustained by TGFβ and concurrently stimulating recruitment of inflammatory cells with GM-CSF by oncolytic viruses would result in improved anti-tumor responses. Thus, we developed a new oncolytic adenovirus rAd.sT.GM (AMUN-003) that expresses both sTGFβRIIFc (a TGF-β decoy), and GM-CSF and tested it in a mouse TNBC (4T1) subcutaneous model. rAd.sT.GM was safe to use and more effective in controlling tumor progression and lung metastasis following intratumoral injections when compared to control adenoviruses without modifications. In the same model, combinations of immune checkpoint inhibitor (ICI) therapy with rAd.sT.GM resulted in better inhibition of tumor growth and metastasis. Furthermore, we examined key immune response and prognosis biomarkers in sera, lungs, spleens, and tumors to evaluate the treatment efficacy. We found several key anti-tumor Th1 cytokines such as IL-2, IL-4, and IFN-γ, were stimulated by the combination therapy either systemically or in tumors or both, as well as anti-tumor biomarkers such as Granzyme B and Perforin. These results support advancement to clinical testing with the combination therapy of rAd.sT.GM and ICIs for TNBC patients.

e23564 Background: Prior studies have shown response to immune checkpoint inhibitors (ICI) in a variety of sarcoma subtypes, however, much is still unknown about ICI use in specific sarcoma subtypes due to disease rarity. Patients (pts) are often treated with these agents as part of clinical trials, and real world data in the community setting is lacking. The aim of this study is to report real world efficacy and safety of ICI in sarcoma either alone or with radiation (RT) and/or surgery. Methods: A retrospective cohort review was conducted to identify pts with soft tissue and bone sarcoma who were administered ICI at Kellogg Cancer Center at NorthShore University HealthSystem/Endeavor Health. Pts who received ICI as part of a clinical trial were excluded. Results: A total of 29 pts receiving ICI were identified. Pts had a median of 1 prior systemic therapy. ICI included pembrolizumab (n = 23), nivolumab (n = 5), and ipilimumab/nivolumab (n = 1). Treatment was discontinued in 28 pts due to disease progression (n = 18), toxicities (n = 3), death (n = 2), and maximal response (n = 5). One patient is still undergoing treatment. Median progression-free survival (PFS) was 4.9 months. Median overall survival (OS) was 14 months. Overall response rate (ORR) is 31%. Median duration of response was not reached (44+ months). Complete response (CR) (n = 5) reported in 3 pts with undifferentiated pleomorphic sarcoma (UPS), 1 pt with SMARCA4 deficient undifferentiated sarcoma, and 1 pt with dedifferentiated chondrosarcoma. Partial response (PR) (n = 4) reported in 1 pt with UPS, 1 pt with dedifferentiated liposarcoma, 1 pt with high grade spindle sarcoma of bone, and 1 pt with malignant peripheral nerve sheath tumor. Of those pts with a CR, 2 patients received only pembrolizumab, 1 pt was administered concomitant RT, and 2 pts had administered concomitant surgery. Of the pts who had PR, 3 were also treated with concomitant RT. Grade 3 immune related adverse effects were reported in 5 of the 29 patients. Of these patients, 2 had documented CR and 3 documented PR. Conclusions: This study expands on the real world efficacy of ICI in a variety of sarcoma subtypes. CR and PR rates in this setting were high, and responses were durable, although selection bias for treatment may have played a role. This data supports the treatment of metastatic sarcoma with ICI, especially with concomitant RT and surgery, in a variety of subtypes.

CONTEXT.—:Pembrolizumab is used in patients with metastatic head and neck squamous cell carcinoma contingent upon the programmed death ligand-1 (PD-L1) combined positive score (CPS).OBJECTIVE.—:To compare PD-L1 CPS scores derived from paired resected primary tumors (PTs) and lymph node metastases (LMs) in patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC).DESIGN.—:We identified 38 resected p16+ OPSCCs for which paired PTs and LMs were available. PD-L1 immunohistochemistry using the SP263 antibody clone was done on both the PT and the LM. CPS scoring was performed by 4 observers, and data were analyzed at the CPS cut points of greater than or equal to 1 and 20 in regard to interobserver and interspecimen agreement.RESULTS.—:Overall agreement between consensus CPS scoring of PT and LM was seen in 76% of paired specimens (κ = 0.53). No specimen received a negative consensus score. Interobserver agreement for both PT and LM was fair to substantial (κ = 0.54 and 0.51, respectively) and was inferior to that seen in a prospective series of unselected head and neck squamous carcinoma cases evaluated at our institution (κ = 0.84).CONCLUSIONS.—:Given the high rates of interobserver and interspecimen variability, evaluation of additional material or by additional observers may be of value in performing CPS scoring in cases of p16+ OPSCC. This is particularly the case when a negative or low-positive result is being evaluated in a patient who is otherwise a good candidate for immunotherapy.

Significant biological processes (FDR<0.05) enriched in the 1,015 genes co-clustered with known T cell gene signatures. Among 1,015 genes, 771 were associated with GO annotation in DAVID database v6.7. Count: number of genes from my list that are associated with this GO term. List Total: total number of genes in my list. Pop Hits: total number of genes associated with this GO term from the database. Pop Total: total number of genes in the database. Fold Enrichment: relative enrichment ratio, calculated by (Count)/(List Total) divided by (Pop Hits)/(Pop Total).

PURPOSE Combination of antiprogrammed cell death protein-1 (PD-1) plus anti–cytotoxic T-cell lymphocyte-4 (anti-CTLA-4) immunotherapy shows greater response rates (RRs) than anti-PD-1 antibody alone in melanoma, but RR after initial anti-PD-1 and programmed death ligand-1 (PD-L1) antibody progression awaits robust investigation. Anti-CTLA-4 antibody alone after anti-PD-1/L1 antibody progression has a historical RR of 13%. We report the results of the first prospective clinical trial evaluating ipilimumab 1 mg/kg plus pembrolizumab following progression on anti-PD-1 immunotherapy. METHODS Patients with advanced melanoma who had progressed on anti-PD-1/L1 antibody as immediate prior therapy (including non–anti-CTLA-4 antibody combinations) were eligible. Patients received pembrolizumab 200 mg plus ipilimumab 1 mg/kg once every 3 weeks for four doses, followed by pembrolizumab monotherapy. The primary end point was RR by irRECIST. After 35 patients, the trial met the primary end point and was expanded to enroll a total of 70 patients to better estimate the RR. RESULTS Prior treatments included 60 on anti-PD-1 antibody alone and 10 on anti-PD-1/L1 antibody–based combinations. Thirteen patients had progressed in the adjuvant setting. The median length of prior treatment with anti-PD-1/L1 antibody was 4.8 months. Response assessments included five complete and 15 partial responses, making the irRECIST RR 29% among the entire trial population. The median progression-free survival was 5.0 months, and the median overall survival was 24.7 months. The median duration of response was 16.6 months. There was no difference in median time on prior anti-PD1/L1 or time to PD1 + CTLA4 initiation between responders and nonresponders. Grade 3-4 drug-related adverse events occurred in 27% of patients. Responses occurred in PD-L1–negative, non-T-cell–inflamed, and intermediate tumor phenotypes. CONCLUSION To our knowledge, this is the first prospective study in melanoma of pembrolizumab plus low-dose ipilimumab after anti-PD-1/L1 immunotherapy failure, demonstrating significant antitumor activity and tolerability.

OBJECTIVE:To test feasibility and preliminary efficacy of a couple-based supportive communication (CSC) intervention for head and neck cancer (HNC) delivered during patients' oncology treatment.METHODS:Twenty couples were randomly assigned to either a four-session CSC or a treatment-as-usual (TAU) condition. The CSC intervention primarily focused on increasing couple emotional disclosure, supportive listening, and social support. Patients and partners completed measures of individual and relationship functioning at baseline, post-intervention, and 6-month follow-up.RESULTS:Ninety-eight percent of CSC sessions were completed and couples reported high levels of satisfaction with the intervention. Between-group effect sizes indicated that patients and partners in CSC reported improvements in individual and relationship functioning, relative to those in the TAU condition.CONCLUSIONS:A couple-based communication intervention delivered during oncology treatment is feasible and acceptable in the context of HNC and may lead to improvements in individual and relationship functioning. Preliminary efficacy results are interpreted in the context of social-cognitive processing and intimacy theories.TRIAL REGISTRATION:The trial was registered on www.clinicaltrials.gov (NCT01785576) first posted on February 7, 2013.

10004 Background: Combination PD1 + CTLA4 antibodies (Abs) shows greater response rate (RR) versus PD1 Ab alone in MEL, but RR after initial PD1 Ab progression awaits robust investigation. CTLA4 Ab alone after PD1 Ab progression has a historical RR of 13%. We report final results of the first prospective clinical trial evaluating IPI 1mg/kg + PEMBRO immediately following progression on PD1 Ab (NCT02743819). Methods: Patients (pts) with advanced MEL, no prior CTLA4 Ab for metastatic disease, and who had progressed on PD1 Ab as immediately prior therapy (or non-CTLA4 Ab combination) were eligible. Pts received PEMBRO 200 mg + IPI 1 mg/kg Q3W for 4 doses, then PEMBRO alone for up to two years. The primary endpoint was RR by irRECIST. After 35 pts, the study met its primary endpoint with 10/22 evaluable pts achieving a response. The trial was expanded to enroll a total of 70 pts in open-label accrual to further describe the RR for this regimen in an exploratory fashion. The data analysis cutoff was January 30, 2020. Results: 67/70 accrued patients were evaluable for treatment response. Prior treatments included 60 on PD1 Ab alone and 10 on PD1 Ab-based combinations. Of these, 10 pts had progressed in the adjuvant setting. Median length of treatment on prior PD1 Ab was 4.8 months. Response assessments included 4 CR, 17 PR and 16 SD for a RR of 31% (21/67) in evaluable pts, and 30% (21/70) in all enrolled pts. 4 pts with a PR and 6 with SD had unconfirmed responses making the irRECIST response rate 25% (17/67) and 24% (17/70) among evaluable and enrolled pts, respectively. Median progression free survival (PFS) was 4.7 mo (95% CI: 2.8-8.3) and PFS at six months was 45% (95% CI: 33%-57%). 15/70 (21%) pts experienced ≥ grade 3-4 drug-related AEs, the most common being diarrhea, rash and transaminase elevation. PD-L1 positive vs negative status from historical tumor specimens did not associate with RR. Conclusions: This is the largest prospective study of IPI 1mg/kg + PEMBRO, demonstrating significant antitumor activity and tolerability in MEL post-PD1 Ab. Clinical trial information: NCT02743819.

251 Background: A significant number of cancer-directed therapies are associated with cardiotoxicity. This adverse effect is well-established in anthracyclines and anti-HER2 agents. At our ambulatory oncology practice, the recent availability of echocardiograms with strain imaging has prompted an evaluation of current practices for cardiotoxicity monitoring. A review of the electronic health record (EHR) in 2019 found that although our institution maintains high rates of baseline monitoring, follow-up monitoring is not standardized and not consistent between different practices. Methods: A multidisciplinary team was formed to conduct a quality improvement project with the aim of increasing the rate of follow-up monitoring in patients who receive anthracyclines or infusional anti-HER2 agents. A survey of providers identified the potential reasons that follow-up cardiac monitoring was not completed. A Pareto chart showed that lack of familiarity with clinical necessity and appropriate timing were the most common barriers to follow-up monitoring. Our first plan-do-study-act focused on addressing these barriers, and a pilot in breast cancer treatment plans was started. Cardiac monitoring orders were added to curative intent protocols containing doxorubicin, trastuzumab, or pertuzumab. Education was provided to physician and nursing teams regarding utility and timing of cardiotoxicity monitoring. Collaboration with the cardiology group ensured timely access and result turnaround time. Results: An initial review of the EHR was conducted to identify current trends in cardiac monitoring. The review showed that there was an increase in the use of echocardiograms with strain imaging for baseline and follow-up monitoring in our patients. From January to April 2020, there was a total of 102 echocardiogram orders which was a 23% increase compared to the same timeframe in the previous year. The majority (61%) of those echocardiogram orders included strain imaging compared to 8% in the previous year. Review of treatment plan utilization and appropriate timing of cardiac monitoring in breast cancer patients is ongoing. Conclusions: This quality improvement project suggests that efforts to standardize cardiac monitoring practices can be achieved through provider education and workflow modifications. Further long-term review of the EHR will be needed to determine whether the timing of follow-up monitoring is appropriate and to identify what changes to the intervention should be made.

e14088 Background: The checkpoint inhibitor (CPI) immunotherapy class of drugs is redefining how we treat cancer. The US FDA has approved CPI drugs as 1st, 2nd or salvage line after progression on conventional chemotherapy (CTX) for multiple cancers including melanoma, lung, bladder and other cancers. However, many questions remain regarding optimal treatment post-progression. Indeed, it has been noted that the patterns of response and relapse to CPI agents are quite different from those of standard cytotoxic agents and that response to CTX AFTER CPI may be different than in the de novo setting. The purpose of this retrospective analysis is to evaluate the activity (response rate (RR), response duration (DOR) and progression free survival (PFS)) of subsequent CTX after disease progression following treatment with CPI. Methods: In this analysis, patients (pts) were enrolled under an IRB approved waiver of consent. We identified pts treated with CPI agents between Jan, 2011 and Dec, 2018 at a multi-site community cancer program who received subsequent CTX as a result of disease progression (PD). We assessed the RECIST RR to subsequent therapy, DOR from onset of response, and PFS from the onset of post CPI CTX, identifying index lesions from the most recent pre-treatment anatomic scan. Results: A total of 47 cases satisfying the above criteria were found; 31 NSCLC, 8 melanoma, 1 SCLC, 1 GEJ, 1 gastric, 2 head/neck, 1 large cell neuroendocrine tumor, 2 bladder cancer. 25 pts had PD as best response to post-CPI CTX. 9 pts (19%) achieved a partial response (PR) with a median DOR of 99 days. 22 pts achieved a PR or stable disease (SD) for a clinical benefit (CB) rate of 47%. The median duration of CB was 92 days. Of the 9 patients who achieved PR, 5/6 had achieved response to CTX prior to CPI . The median PFS for the entire cohort was 97 days. Conclusions: While an expected RR could not be calculated in this heterogenous group of pts, the number and degree of responses suggests CPI possible “priming” that may enhance response to CTX. Post-CPI CTX may be of value and in this retrospective study of a heterogenous group of pts, responses may be more frequent than expected. A larger further study is warranted.

To evaluate the performance characteristics of PD-L1 immunohistochemistry (IHC) combined positive scoring (CPS) in core biopsies and aspirate cell blocks from patients with head and neck squamous cell carcinoma (HNSqCCa). PD-L1 IHC using the SP263 antibody was performed on 20 paired cases which consisted of a small biopsy and an excisional specimen. The scores were compared at both the 1% and 20% cutpoints. Using the CPS result obtained from the resected specimen or excisional biopsy as the gold standard, PD-L1 IHC performed on the core biopsy or cell block identified 4 of 6 positive cases (66%) at the 20% cutpoint and 12 of 17 (70%) positive patients at the 1% cutpoint. False positive cases were uncommon at both cutpoints. CPS scoring should be used with caution in small biopsies from patients with HNSqCCa. A negative result should prompt consideration of an excisional biopsy and repeat testing.

e14128 Background: Immune checkpoint inhibitors (ICIs) are changing the landscape of treatment in oncology. The use of ICIs is growing rapidly as the indications for these medications broaden and new ICIs become approved. Given the rapid growth and relative infancy of the use of ICIs, much information stands to be gained on their use in the clinical practice setting, especially regarding toxicity. Methods: The primary objective of this project was to examine the incidence and severity of immune-related adverse events (irAEs), after treatment with single-agent or combination ICIs at a multi-site community cancer center. A retrospective chart review was conducted on all patients who had received ipilimumab, nivolumab, pembrolizumab, atezolizumab, or ipilimumab plus nivolumab from May 1, 2011 to June 30, 2017. Data collected included patient demographics, disease state, treatment information, preexisting autoimmune disease, previous immunotherapy, and adverse event details. The results were analyzed using descriptive statistics. Results: Data was collected on 383 patients. Dermatologic irAEs were common across single agent ICIs (overall incidence 23%). Diarrhea and/or colitis incidence was highest with CTLA-4 inhibitor ipilimumab (26% at 3 mg/kg and 22% at 10 mg/kg) versus the other monotherapy PD-1/PDL-1 inhibitors. Endocrinopathies were most common with ipilimumab 10 mg/kg (55%) and pneumonitis incidence was highest with nivolumab (6%). ICI toxicity occurred in 63% of patients with preexisting autoimmune disease versus 54% of those without a baseline autoimmune disease. Incidence of hospitalization and treatment holds due to irAEs was higher with combination therapy (57% and 66%, respectively) than with monotherapy (10% and 24%, respectively). Conclusions: Overall, there was increased incidence in ICI toxicity in patients at this oncology institution versus what has been reported in clinical trials. Patients with preexisting autoimmune diseases appeared to have mainly low-grade toxicities with slightly increased incidence of irAE compared with those without pre-existing autoimmune disease. Treatment holds and hospitalizations were higher in patients treated with combination therapy ICIs compared to monotherapy ICIs.

Background: Brivanib is a selective inhibitor of vascular endothelial growth factor and fibroblast growth factor (FGF) signalling. We performed a phase II randomised discontinuation trial of brivanib in 7 tumour types (soft-tissue sarcomas [STS], ovarian cancer, breast cancer, pancreatic cancer, non-small-cell lung cancer [NSCLC], gastric/esophageal cancer and transitional cell carcinoma [TCC]). Patients and methods: During a 12-week open-label lead-in period, patients received brivanib 800 mg daily and were evaluated for FGF2 status by immunohistochemistry. Patients with stable disease at week 12 were randomised to brivanib or placebo. A study steering committee evaluated week 12 response to determine if enrolment in a tumour type would continue. The primary objective was progression-free survival (PFS) for brivanib versus placebo in patients with FGF2-positive tumours. Results: A total of 595 patients were treated, and stable disease was observed at the week 12 randomisation point in all tumour types. Closure decisions were made for breast cancer, pancreatic cancer, NSCLC, gastric cancer and TCC. Criteria for expansion were met for STS and ovarian cancer. In 53 randomised patients with STS and FGF2-positive tumours, the median PFS was 2.8 months for brivanib and 1.4 months for placebo (hazard ratio [HR]: 0.58, p = 0.08). For all randomised patients with sarcomas, the median PFS was 2.8 months (95% confidence interval [CI]: 1.4-4.0) for those treated with brivanib compared with 1.4 months (95% CI: 1.3-1.6) for placebo (HR = 0.64, 95% CI: 0.38-1.07; p = 0.09). In the 36 randomised patients with ovarian cancer and FGF2-positive tumours, the median PFS was 4.0 (95% CI: 2.6-4.2) months for brivanib and 2.0 months (95% CI: 1.2-2.7) for placebo (HR: 0.56, 95% CI: 0.26-1.22). For all randomised patients with ovarian cancer, the median PFS in those randomised to brivanib was 4.0 months (95% CI: 2.6-4.2) and was 2.0 months (95% CI: 1.2-2.7) in those randomised to placebo (HR = 0.54, 95% CI: 0.25-1.17; p = 0.11). Conclusion: Brivanib demonstrated activity in STS and ovarian cancer with an acceptable safety profile. FGF2 expression, as defined in the protocol, is not a predictive biomarker of the efficacy of brivanib. (C) 2019 The Author(s). Published by Elsevier Ltd.

e18081 Background: CRT is a component of treatment (tx) for LRA SCCHN. High dose cisplatin (HDC) on weeks 1, 4, 7 is a standard but toxic regimen. Additionally, many cases of SCCHN are now attributable to HPV with better prognosis. A less toxic WC regimen has been used as an alternative for HDC. We sought to review our experiences with this regimen. Methods: We reviewed our outcomes of 298 consecutive LRA SCCHN patients (pts) treated with IMRT based therapy from 7/2003 through 7/2015 via data warehouse extraction and chart review. Tx setting was noted as definitive or post-op. Chemotherapy was categorized as induction yes/no, and CRT in 4 groups (none (n = 60 )/WC (n = 121 )/ FHX (5FU, hydroxyurea, taxol( n = 35 )/

9514 Background: Immunotherapy with anti-PD-1 + CTLA-4 Abs improves response rates over anti-PD-1 Ab alone; however, the utility of this combination after first line anti-PD-1 is unknown. We report the first prospective data evaluating pembro + low dose ipi immediately following progression on anti-PD-1 (NCT02743819). Methods: Patients (pts) with mel and measurable disease, no autoimmunity, and no prior anti-CTLA-4 who had progressed immediately prior on an anti-PD-1 (or non-CTLA4 combination) were eligible. Prior BRAF inhibitor was allowed (none received it). Pts received pembro 200 mg + ipi 1 mg/kg Q3W for 4 doses, then pembro alone. The primary endpoint was response rate (RR) as assessed by irRECIST. An optimal Simon two-stage design was employed to test the null hypothesis of a 10% RR vs 30% alternative (1-sided alpha 0.10, 90% power, ≥2/12 RR to continue to total of ≥6/35). The data analysis cutoff date was January 2, 2018. Results: 22 patients have been accrued with 17 evaluable for the primary endpoint (4 have not yet had their first imaging evaluation and 1 was not enrolled). Prior treatment included 21 on anti-PD-1 alone and 1 on combination with IDO inhibitor. Median length of treatment on prior anti-PD-1 was 5.6 months among all 22 pts. The study met its interim efficacy analysis with 5/12 responses to move to stage 2. Among the 17 response-evaluable pts there were 2 CR, 6 PR (47% RR), and 5 SD for disease control rate (DCR) of 76% and rejection of the null hypothesis. Progression-free survival at 6 months was 75% (CI 47%-90%). All responses are ongoing. At last follow-up, 8 pts have gone off treatment with 14/22 (64%) having any drug-related and 3/22 (14%) ≥ grade 3-4 drug-related AE (hyperglycemia, acute kidney injury and skin tissue disorder, diarrhea and rash acneiform). Among 11 response-evaluable pts with staining results currently available, RR and DCR were 67% and 100% in PD-L1+ (n = 3) and 50% and 88% in PD-L1 negative (n = 8) tumors. Further biomarker analysis is underway. Conclusions: Pembro + 1 mg/kg ipi is tolerable and has antitumor activity in pts with mel who have progressed immediately prior on an anti-PD-1 Ab. The trial sample size has been expanded to further explore this regimen. Clinical trial information: NCT02743819.

38 Background: To meet Commission on Cancer accreditation requirements, cancer programs must implement processes to monitor the dissemination of survivorship care plans (SCP) for patients with Stages I-III cancers who were treated with curative intent and completed active therapy. Challenges of SCP delivery across disease sites include lack of designated/trained staff, time burden, knowledge of current evidence-based guidelines, and sustainability. We describe the challenges NorthShore University HealthSystem Kellogg Cancer Center (NKCC) and their Living in the Future (LIFE) Cancer Survivorship Program faced in meeting this standard and how evolving the SCP delivery process has resulted in a sustainable model. Methods: LIFE implemented a technology-based SCP tool using a centralized consultative model led by a nurse practitioner (NP) with specialized survivorship training. Physicians referred eligible patients to the survivorship clinic for an education visit where they received a SCP from the NP. Since the centralized model was dependent on one person for delivery, a more sustainable model was needed. NKCC transitioned to a decentralized process, moving SCP creation and delivery responsibility to all oncology care providers (OCPs). Although not all OCPs had specialized survivorship training, care quality was supported by automated SCP creation based on evidence-based care recommendations embedded in the technology. Results: To date, 143 evidence-based SCPs have been delivered since tool implementation in April 2017. During the centralized model (April 25– June 30) 67 SCPs were created by the lead LIFE NP; 76 were created during the decentralized process while the lead NP was on leave (July 3 – Oct 1). By using a technology-based SCP, OCPs incorporated SCP delivery into their workflow and no longer had to refer patients to a separate clinic. Conclusions: This project demonstrates the feasibility of a sustainable, decentralized process using a technology-based SCP as an option for augmenting centralized SCP delivery. A comparable number of patients received a SCP during both processes with an equivalent number of SCPs being delivered via the decentralized model by OCPs supported by evidence-based technology.

6042 Background: Radiation (RT) or (CRT) is a component of treatment (tx) for locoregionally advanced (LA) SCCHN. ALC and lymphocyte subsets are known to decrease as a result of RT for SCCHN. The changes in and variables affecting ALC during or after RT/CRT are not well described. Methods: We retrospectively reviewed the ALC of 298 consecutive patients (pts) treated with IMRT based therapy for LASCCHN from 7/2003-7/2015. ALC was categorized using a prespecified algorithm at day 0 of RT, weeks (wk) 1,2,3,4,5,6,7,8,9, months (mo) 3, 6, 12 and years (yr) 2,3,4,5. Chemotherapy (CT) was categorized as induction (IC) yes/no and CRT as one of 4 groups: none/weekly cisplatin/ FHX (5FU, hydroxyurea, taxol)/”other”, and RT was recorded as unilateral or bilateral neck tx. Regression analysis was used to assess survival as a function of ALC. VZV (shingles) infection was noted and recorded. Results: ALC nadir for the entire group occurred at week 9 at a mean level of 0.4 (CTCAE 4.03 grade 3, normal range 1.0 - 4.0 103/uL ) for CRT patients and 0.76 for RT only patients (p = 0.016). At yr 1, ALC ranged from 0.83-1.04 (p = 0.2) amongst 4 groups. By year 5, ALC had only recovered to 69% of baseline with no significant differences between groups. The use of IC did not affect nadir ALC. Pts receiving bilateral neck RT vs. unilateral had significantly lower mean ALC nadirs from wk 3-9 (wk 9: 0.38 vs. 0.88 p < 0.001) but not after 3 mo. ALC nadir had no effect on relapse or survival parameters. 19 pts had documented cases of shingles (VZV) occurring at a median time of 10 mo. There was no effect on nadir ALC by p16 status for oropharynx pts. Conclusions: Pts undergoing RT or CRT for SCCHN have a quick and severe ALC nadir which never recovers to normal. CRT compared with RT decreased the severity of the nadir but not recovery. IC does not impact ALC, but bilateral neck RT leads to a deeper nadir than unilateral. ALC nadir does not affect survival. VZV could be a related adverse event as it follows CRT in at least 6% of patients at a median of 10 mo. The severe and sustained ALC nadir may also have important effects on the timing of the use of checkpoint inhibitor therapy during RT or CRT.

BACKGROUNDCancer and its treatment lead to increased financial distress for patients. To the authors' knowledge, to date, no standardized patient‐reported outcome measure has been validated to assess this distress.METHODSPatients with AJCC Stage IV solid tumors receiving chemotherapy for at least 2 months were recruited. Financial toxicity was measured by the COmprehensive Score for financial Toxicity (COST) measure. The authors collected data regarding patient characteristics, clinical trial participation, health care use, willingness to discuss costs, psychological distress (Brief Profile of Mood States [POMS]), and health‐related quality of life (HRQOL) as measured by the Functional Assessment of Cancer Therapy: General (FACT‐G) and the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires. Test‐retest reliability, internal consistency, and validity of the COST measure were assessed using standard‐scale construction techniques. Associations between the resulting factors and other variables were assessed using multivariable analyses.RESULTSA total of 375 patients with advanced cancer were approached, 233 of whom (62.1%) agreed to participate. The COST measure demonstrated high internal consistency and test‐retest reliability. Factor analyses revealed a coherent, single, latent variable (financial toxicity). COST values were found to be correlated with income (correlation coefficient [r] = 0.28; P<.001), psychosocial distress (r = ‐0.26; P<.001), and HRQOL, as measured by the FACT‐G (r = 0.42; P<.001) and by the EORTC QOL instruments (r = 0.33; P<.001). Independent factors found to be associated with financial toxicity were race (P = .04), employment status (P<.001), income (P = .003), number of inpatient admissions (P = .01), and psychological distress (P = .003). Willingness to discuss costs was not found to be associated with the degree of financial distress (P = .49).CONCLUSIONSThe COST measure demonstrated reliability and validity in measuring financial toxicity. Its correlation with HRQOL indicates that financial toxicity is a clinically relevant patient‐centered outcome. Cancer 2017;123:476–484. © 2016 American Cancer Society.