Search

TPS277 Background: There is a need to develop novel immunotherapeutic approaches to enhance responses to immune checkpoint blockade. REGN7075 is a human costimulatory bispecific antibody designed to bridge epidermal growth factor receptor (EGFR)-expressing tumor cells with CD28-positive T cells to support further T-cell activation by endogenous tumor antigens. Methods: This is an open-label, Phase 1/2, first-in-human study evaluating the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of REGN7075 (EGFRxCD28) alone and in combination with cemiplimab (anti-programmed cell death [PD]-1) in patients with advanced solid tumors (NCT04626635). This study includes a dose-escalation (Bayesian optimal interval design; Part 1) and a dose-expansion phase (Part 2). Patients must have a protocol-defined advanced solid tumor, have an Eastern Cooperative Oncology Group performance status of 0 or 1, and be naive to anti–PD-1/anti–PD-ligand(L)1 therapy in the dose-expansion phase. In Part 1, heavily pre-treated patients with advanced solid tumors receive a lead-in of REGN7075 monotherapy every week for 3 weeks followed by combination therapy with cemiplimab 350 mg every 3 weeks. Planned dose levels (DLs) of REGN7075 are 0.03, 0.1, 0.3, 1, 3, 10, 30, 100, 300, and 900mg. Once the recommended Phase 2 dose is determined in Part 1, five tumor-specific expansion cohorts will be opened in Part 2: colorectal cancer (microsatellite stable [MSS-CRC]), non-small cell lung cancer (NSCLC, PD-L1 ≥50%), triple-negative breast cancer, cutaneous squamous cell carcinoma, and head and neck squamous cell carcinoma (PD-L1 combined positive score ≥1). Patients with MSS-CRC with RAS or BRAF wild type mutations must have received anti-EGFR therapy or anti-vascular endothelial growth factor (VEGF therapy). Primary endpoints are safety and tolerability of REGN7075 alone or in combination with cemiplimab for Part 1, and objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 for Part 2. For Part 2, a secondary objective is to assess the effect of REGN7075 on patient-reported outcomes as measured by several validated instruments including the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and EORTC QLQ-CR29 (CRC patients only). Approximately 400 patients will be enrolled in this phase 1/2 study, including ~80 patients in Part 1 and ~320 patients in Part 2 (including ~70 in the CRC cohort). As of September 13, 2022, 30 patients were treated in the dose-escalation phase, up to the 300 mg DL for REGN7075 in combination with cemiplimab. This study is ongoing and currently open to enrollment. Clinical trial information: NCT04626635 .

e18742 Background: HHIs are the only approved 1L systemic Tx for aBCC. Many pts develop resistance or are intolerant to HHIs and may require second-line (2L) Tx. Little is known about patient outcomes following HHI discontinuation. In this study, we describe characteristics and outcomes among pts with aBCC who discontinued 1L HHIs due to progression or toxicity. Methods: In this retrospective cohort study, we identified adult pts diagnosed with aBCC who discontinued 1L HHI monotherapy between January 2012 and November 2019 in The US Oncology Network (Network), a community-based network of > 450 oncology clinics. Pts with ≥2 Network visits and no Tx for other primary malignancy 3 years prior to index date were included. Structured and unstructured data in the electronic health records were used to extract information on pt characteristics and outcomes. Pts were grouped based on initiation of 2L systemic Tx post-HHI discontinuation into 2L initiators and 2L non-initiators. 2L non-initiators were followed for ≥90 days post-HHIs discontinuation, and those undergoing surgery or radiation during this period (i.e. potential neoadjuvant HHI use) were excluded. Index date was date of 2L Tx initiation for 2L initiators and 90 days post 1L HHI discontinuation for 2L non-initiators. Pts were followed from index date until death, Tx initiation for another primary cancer, loss to follow-up, or end of study (February 1, 2020), whichever occurred first. Pt disposition and outcomes were described separately for each group. Results: We identified 73 aBCC pts who discontinued 1L HHI monotherapy during the specified period. Of those, 19 (26%) pts (4 [21%] 2L initiators and 15 [79%] 2L non-initiators) were included in the study: 12 (63%) were male and 3 (21%) were metastatic at diagnosis, with a mean age of 73 years. Median (range) follow-up time from index date was 10 (3‒42) months for 2L non-initiators and 6 (1‒61) months for 2L initiators. Fourteen (74%) pts discontinued HHI due to toxicity (all 2L non-initiators) and 5 (26%) due to progression (4 2L initiators and 1 2L non-initiator). Median time to discontinuation of 1L HHI was 7 (2‒9) months in 2L non-initiators and 9 (7‒42) months in 2L initiators. 2L initiators received subsequent Tx 2‒130 days following discontinuation of 1L HHI. Time to discontinuation of 2L Tx ranged 4–11 months. Six deaths (32%) were observed during study period (5 2L non-initiators and 1 2L initiator). Conclusions: The short duration of 1L HHI Tx in our small cohort of aBCC pts who did not respond to and/or tolerate HHI is consistent with previous findings. During the study period, limited therapeutic options existed post-HHI, highlighting the unmet need for more effective Tx strategies in a 2L aBCC setting.

e18740 Background: HHIs are the only approved 1L systemic Tx for aBCC and Tx options following HHI Tx failure are limited. The objective of this study was to assess frequency, characteristics, and subsequent Tx patterns of pts with aBCC discontinuing 1L HHIs due to toxicity or disease progression. Methods: We conducted a retrospective cohort study using electronic health records of pts treated in The US Oncology Network (Network), a community-based network of > 450 oncology clinics. We identified adults (18+ years) with aBCC, not treated for another primary malignancy in the past 3 years, with ≥2 Network visits who discontinued 1L HHI monotherapy between January 2012 and November 2019 due to documented toxicity or progression without evidence of complete response (CR) who subsequently initiated second-line (2L) systemic Tx (2L initiators) or not (2L non-initiators). To exclude pts potentially using neoadjuvant HHIs, we required 2L non-initiators to be followed for ≥90 days after HHI discontinuation and excluded pts who underwent surgery or radiation during this period. Index date was Tx initiation for 2L initiators and 90 days after HHI discontinuation for 2L non-initiators. We describe cohort attrition and characteristics of 2L initiators and 2L non-initiators as well as Txs initiated among 2L initiators. Results: We identified 138 aBCC pts treated with HHIs regardless of line of therapy with fully accessible charts: 115/138 (83.3%) received HHIs as 1L systemic therapy for aBCC; 73/115 (63.5%) discontinued 1L HHIs; 37/73 (50.7%) discontinued due to documented toxicity or progression without evidence of CR. 4/37 pts (10.8%) initiated 2L systemic Tx (1 carboplatin & paclitaxel; 1 cemiplimab; 1 nivolumab; 1 pembrolizumab) within a median of 75 days (range: 2‒130) from HHI discontinuation. 2L initiators were 68.7 years of median age (range: 48.4‒71.1); 100% female; 75% White; 75% immunocompetent; 100% treated with 1L vismodegib for a median of 8.6 months (range: 6.8‒42.2); 100% discontinued 1L HHIs due to documented disease progression. We identified 15 2L non-initiators; median age 80.2 years (range: 49.6‒90+); 20% female; 100% White; 86.7% immunocompetent; 100% treated with 1L vismodegib for a median of 6.8 months (range: 1.9‒20.6); 93.3% discontinued 1L HHIs due to documented toxicity and 6.7% due to progression. Conclusions: In this small cohort of aBCC pts discontinuing 1L HHIs, ̃50% discontinued due to toxicity or disease progression. There was no clear standard of care among pts who experienced HHI Tx failure, with only a minority initiating subsequent 2L Tx. Effective Tx strategies for pts who do not respond to or cannot tolerate HHIs are needed.

9566 Background: Cemiplimab-rwlc is the first immunotherapy to receive approval in the US, fully for pts with laBCC and accelerated for metastatic BCC, post hedgehog inhibitors or for whom hedgehog inhibitors are not appropriate. Cemiplimab resulted in clinically meaningful anti-tumor activity in pts with laBCC who progressed on or were intolerant to hedgehog inhibitor therapy (NCT03132636). This analysis evaluated HRQoL in these pts. Methods: Adults with laBCC and ECOG performance status ≤1 (n=84) received IV cemiplimab 350 mg Q3W for up to 9 treatment cycles. At baseline (BL) and day 1 of each cycle (C), pts completed EORTC QLQ-C30 and SKINDEX-16 questionnaires that assess Global Health Status (GHS)/QoL, functioning, and BCC-related symptoms. Mixed-effects repeated measures (MMRM) models were used to estimate least squares (LS) mean (standard error [SE]) change from BL during treatment (i.e., across C2 to C9); changes ≥|10| points were considered clinically meaningful. Responder analyses were conducted in pts with non-missing data from BL to determine the proportions with clinically meaningful improvement or deterioration, or stability on QLQ-C30 and SKINDEX-16 at C2 and C9; a 10-point threshold was considered meaningful for both instruments. Results: BL scores showed moderate to high levels of functioning and low symptom burden. In MMRM models, overall changes from BL on QLQ-C30 indicated stability for GHS/QoL and all scales except for clinically meaningful worsening of fatigue (LS mean [SE] change 12.5 [3.9]; P

9078 Background: Cemiplimab, a PD-1 inhibitor, improved survival and progression-free survival vs platinum doublet chemotherapy (chemo) in patients (pts) with advanced NSCLC and PD-ligand(L)1 expression ≥50% in the EMPOWER-Lung 1 Phase 3 study (NCT03088540). Since pts with advanced NSCLC have a high symptom burden that adversely impacts QoL and functioning, these outcomes were evaluated as secondary endpoints in the clinical trial. Methods: Pts with advanced NSCLC with PD-L1 expression ≥50% and ECOG performance status ≤1 were randomized to IV cemiplimab 350 mg Q3W (n=356) or platinum doublet chemo (n=354). At baseline (BL) and day 1 of each treatment cycle (C) to C15, pts were administered the EORTC core questionnaire (QLQ-C30) and its lung cancer specific module (QLQ-LC13) to assess symptoms, functioning, and Global Health Status (GHS)/QoL. In the intent-to-treat population, mixed-effects repeated measures models were used to estimate least squares (LS) mean change from BL on all scales. Kaplan–Meier analysis estimated time to definitive deterioration, defined as worsening ≥10 points from BL observed at all subsequent time points or patient withdrawal after worsening; hazard ratios (HR) with 95% CIs estimated the likelihood of definitive deterioration. Results: BL scores showed moderate to high levels of functioning and low symptom burden. Cemiplimab-treated pts had lower likelihood of definitive deterioration vs chemo on key symptoms of dyspnea, cough, pain in chest, pain in other body parts, fatigue, nausea/vomiting, appetite loss, constipation, and diarrhea vs chemo (all P

e19397 Background: Cemiplimab is a high-affinity, human, hinge-stabilized, monoclonal antibody that potently blocks the interactions of programmed cell death-1 (PD-1) with programmed cell death ligand-1 (PD-L1) and PD-L2. In September 2018, cemiplimab-rwlc became the first systemic therapy approved by the US Food and Drug Administration for the treatment of patients with advanced CSCC ineligible for curative surgery or radiotherapy. In a single-arm Phase II study (NCT02760498), cemiplimab demonstrated substantial antitumor activity, durable responses, and acceptable safety profile in patients with advanced CSCC. The aim of this analysis was to evaluate the cost-effectiveness of cemiplimab in patients with advanced CSCC from a US payer perspective. Methods: A partitioned survival model was developed to assess the cost-effectiveness of cemiplimab versus historical standard of care (SOC). All inputs were identified based on a systematic literature review (SLR), which was supplemented by expert opinion where necessary. The clinical inputs for cemiplimab were based on the individual patient data from the cemiplimab Phase II trial, whereas for SOC, the analysis was based on a pooled analysis of single-arm clinical trials and retrospective studies evaluating chemotherapy and epidermal growth factor receptor inhibitors (cetuximab, erlotinib, and gefitinib) identified via the SLR (6 of the 27 included studies). Overall survival and progression-free survival were extrapolated over a lifetime horizon using parametric functions consistent with guidance from the National Institute for Health and Care Excellence Decision Support Unit. Costs were included for drug acquisition, drug administration, management of adverse events, subsequent therapy, disease management, and terminal care. Unit costs were based on published 2019 US list prices. Results: In the base case, cemiplimab versus SOC resulted in an incremental cost-effectiveness ratio (ICER) of $99,024 per quality adjusted-life year (QALY), where incremental costs and QALYs were $372,425 and 3.76, respectively. At a willingness-to-pay threshold of USD $150,000 per QALY, the probabilistic sensitivity analysis suggests a 91% probability that cemiplimab is cost-effective when compared to SOC. Scenario analyses resulted in ICERs ranging from $90,326 to $147,944. Conclusions: Compared with historical SOC, cemiplimab is a cost-effective use of US payer resources for the treatment of advanced CSCC and is expected to provide value for money.

e19351 Background: CAR T, approved in the US as of October 2017, impacted the treatment landscape for patients with relapsed or refractory (R/R) DLBCL after ≥2 lines of therapy, but there is little known about real-world (RW) treatment patterns in patients who fail or do not respond to CAR T. No treatments of proven benefits are available after CAR T treatment failure. The objective of this study was to describe RW treatment patterns after CAR T. Methods: From MarketScan Commercial/Medicare claims databases (2017‒2018) we identified adult DLBCL patients who received approved CD19-directed CAR T (treatment date = index date). Eligible patients had ≥6 months continuous health plan enrollment prior to index date (i.e. baseline period) and were followed until plan disenrollment or December 31, 2018. Patients with a diagnosis of acute lymphoblastic leukemia over the baseline period were excluded. We identified the first and second treatments after CAR T with systemic chemotherapy, targeted therapy, immunotherapy, hematopoietic stem cell transplant (SCT), radiation therapy (RT), or a second round of CAR T therapy. Kaplan–Meier estimators were used to estimate risk of subsequent treatment and time to next treatment. Results: We identified 56 patients with DLBCL treated with CAR T (mean age [SD]: 57.3 years [9.9]; 23.2% female; 80.4% commercially insured). All patients received CAR T in the inpatient setting, median (Q1‒Q3) length of stay was 15 days (12‒19). Out of 56 patients, 19 initiated a treatment following CAR T; risk of subsequent treatment at 6 months post index was 45.6% (95% CI: 25.4‒60.4%) and median days from CAR T to next treatment was 233 days (95% CI: 139‒NA). Out of 19 patients, 3 initiated a second treatment following CAR T, within 8‒69 days of the first treatment. Over a median (Q1‒Q3) follow-up of 139.5 days (90.5‒194) following CAR T, of the 19 patients treated after CAR T, 57.9% were treated with immunotherapy, 36.8% with RT, 26.3% with targeted therapy, 21.1% with SCT, 15.8% with chemotherapy, and 0% with a second round of CAR T. Conclusions: There are few multicenter studies reporting RW treatment patterns in patients who received CAR T. In this study, risk of subsequent treatment at 6 months following CAR T in a RW setting was almost 50%. Although limited by duration of follow-up, our results suggest that additional, effective salvage treatment strategies are needed for patients who do not respond to CAR T or do not achieve a durable response to CAR T. Updated results using 2019 data will be presented.

10033 Background: Cemiplimab-rwlc (cemiplimab), a PD-1 Inhibitor, showed a robust clinical response in patients (pts) with metastatic (mCSCC) or locally advanced (laCSCC) CSCC not eligible for curative surgery/radiation. This post hoc exploratory analysis examined data from the EORTC cancer specific 30-item HRQL questionnaire (QLQ-C30) for pts participating in a cemiplimab phase 2 clinical trial (clinicaltrials.gov NCT02760498). Methods: Adults (N = 193) with invasive CSCC, ≥1 lesion and ECOG performance status ≤1 received IV cemiplimab 3mg/kg q2w (mCSCC n = 59; laCSCC n = 78) or 350mg q3w (mCSCC n = 56). At baseline (BL) and day 1 of each treatment cycle, pts were administered the QLQ-C30. Mixed effects repeated measures (MMRM) models were used to estimate mean change from BL to cycle 5 (C5) for domains/items of the QLQ-C30. For pts with data from BL to C5, the proportion who reported clinically meaningful improvement or worsening (≥10 points) or maintenance (those who did not have ≥10 point change) on each domain was determined for combined and individual treatment groups. Results: BL scores indicated moderate to high levels of functioning and low symptom burden. From BL to C5, a clinically meaningful improvement in pain score was observed (least squares [LS] mean [standard error] change -12.1 [2.1]; P< .0001); other domains/items remained stable or showed a trend towards improvement (LS mean changes < 10 points). By C5, the majority of pts experienced clinically meaningful improvement or remained stable across key domains (Table). Similar findings were observed on individual symptoms (85%-94% for dyspnea, nausea/vomiting, diarrhea, constipation, appetite loss) and in each treatment group. Conclusions: Cemiplimab-treated patients achieved a clinically meaningful reduction in pain and most pts either improved or maintained their HRQL, function with low symptom burden. Clinical trial information: NCT02760498. [Table: see text]

e21034 Background: CSCC is the second most common skin cancer. Most CSCC cases can be cured with surgical excision alone (5-year cure rate > 95%). We sought to evaluate patterns of major surgeries among patients with CSCC, overall and among those requiring systemic therapy. Methods: From Truven MarketScan claims data, we identified patient’s first CSCC diagnosis between 2013 and 2018 and required that they be continuously enrolled in their healthcare plan and have no CSCC diagnosis in the previous 12 months. Major surgeries included facial excisions over 3.1 cm, parotidectomy, removal of ear/eye/nose, amputations, craniectomy, excision of extracranial nerves, sentinel lymph node biopsy, lymphadenectomy, complex repairs of over 7.5 cm, integra, free flaps, and large grafts over 20 sq cm. Risk of a major surgery was assessed using Kaplan-Meier estimators for patients with CSCC overall and for those who received prior or concurrent systemic therapy, stratified by immune status. Results: A total of 240,122 patients with CSCC (mean age [SD]: 67.7 [12.9] years; male: 56.5%; immunocompromised: 12.4%) were identified with a mean (SD) follow-up of 1.34 (1.15) years. Risk of major surgery (95% confidence interval [CI]) at 1 and 2 years was 15.1% (14.9–15.2) and 18.6% (18.4–18.8), respectively. 782 patients received prior or concurrent systemic therapy, of which 22.4% (n = 175) were immunocompromised. Among those who received systemic therapy, 1- and 2-year risks (95% CI) were 8.4% (5.8–11.0) and 14.2% (10.0–18.2) for immunocompetent and 14.1% (7.7–20.0) and 19.3% (10.7–27.0) for immunocompromised patients, respectively. Conclusions: Over 2 years, approximately one in five patients with CSCC will undergo at least one major surgery. Prior or concurrent treatment with systemic therapy did not appreciably diminish the risk of requiring major surgery. For patients who received systemic therapy, the 1-year and 2-year risk of major surgery was higher for immunocompromised patients compared to immunocompetent patients.

e18703Background: Unlike other cancers, information on CSCC is not captured in national cancer registries, and little is known about the management and costs of CSCC. In contrast, more is known abo...