Abstracts J Immunother : first published as 10.1136/jitc-2020-SITC2020.0352 on 10 December 2020. Downloaded from samples are collected to evaluate T cell responses using flow or without cetuximab), disease progression within 12 weeks cytometry, ELISA, ELISPOT. from the last dose of treatment with 2 doses of a PD-(L)1 Results As of July 23, 2020, 9 patients were enrolled. Median inhibitor, measurable disease based on RECIST v1.1 as con- duration of ongoing anti-PD therapy was 37 weeks (range 20– firmed by BICR, ECOG performance status of 0 or 1, and no 101). The combination was well-tolerated with no DLTs and major blood vessel invasion/infiltration. Patients will be mostly Grade 1–2 unrelated adverse events. Two Grade 3 randomized 3:3:2 to pembrolizumab (200 mg IV Q3W for up events were reported: hypertension (not related) and dehydra- to 35 cycles) plus lenvatinib (20 mg orally once daily), investi- tion (related), the later reported as serious adverse event. Of gator’s choice of SOC (, , seven patients eligible for efficacy analysis, one patient with cetuximab, or ), or lenvatinib monotherapy (24 PD-L1 negative disease had a partial response with a reduc- mg orally once daily). Randomization will be stratified by PD- tion of 29% at week 6 with deepening of the response to L1 tumor proportion score (<50% versus 50%) and ECOG 43% at week 12 and one patient with progressive disease at performance status (0 versus 1). Treatment will continue until study entry had stabilization of disease at week 6 and 12. centrally verified disease progression, unacceptable toxicity, or Another two patients had stable disease for 30+ weeks and decision to withdraw. Patients in the chemotherapy and lenva- three patients had PD. Additional efficacy and immunological tinib monotherapy arms may be eligible to receive pembrolizu- analyses are ongoing. mab plus lenvatinib upon disease progression. The primary Conclusions Early data show that the combination of SNS-301 endpoint is ORR according to modified RECIST v1.1 as and pembrolizumab has manageable toxicity and capacity to assessed by BICR. Secondary endpoints include PFS, OS, achieve long-term disease stability and objective tumor DOR, and safety. Interim futility analysis will be conducted responses. for the lenvatinib monotherapy arm. Tumor imaging by CT or Trial Registration NCT04034225 MRI will be performed 6 weeks after randomization, every 6 Ethics Approval This study has been approved by WIRB weeks through year 1, and every 9 weeks thereafter. Safety (20190628) as well as several institutional IRBs. will be monitored throughout the study and for 30 days after treatment end (90 days for serious AEs if no new anticancer http://dx.doi.org/10.1136/jitc-2020-SITC2020.0349 treatment is initiated, and at any time if the AE is considered treatment-related). Recruitment is ongoing; Planned enrollment is ~400 patients. Results N/A 351 PEMBROLIZUMAB PLUS LENVATINIB VS Conclusions N/A

CHEMOTHERAPY AND LENVATINIB MONOTHERAPY FOR Trial Registration ClinicalTrials. gov Identifier, NCT04428151 copyright. RECURRENT/METASTATIC HEAD AND NECK SQUAMOUS Ethics Approval The study and protocol were approved by the CELL CARCINOMA THAT PROGRESSED ON PLATINUM Institutional Review Board or ethics committee at each site. THERAPY AND IMMUNOTHERAPY: LEAP-009 Consent All patients provided written informed consent to 1Kevin Harrington*, 2Ezra Cohen, 3Lilian Siu, 4Danny Rischin, 5Lisa Licitra, 6Jan Vermorken, participate in the clinical trial. 7Quynh-Thu Le, 8Makoto Tahara, 9Jean-Pascal Machiels, 10Natalyn Hawk, 11Joy Ge, 11Behzad Bidadi, 11Ramona Swaby, 12Barbara Burtness. 1The Institute of Cancer Research, REFERENCE London, UK; 2University of California San Diego and Moores Cancer Center, La Jolla, CA, 1. Matthew H Taylor, Chung-Han Lee, Vicky Makker, et al. Phase IB/II trial of lenva- USA; 3University Health Network, Toronto, ON, Canada; 4Peter MacCallum Cancer Centre, tinib plus pembrolizumab in patients with advanced renal cell carcinoma, endome- 5 trial cancer, and other selected advanced solid tumors. J Clin Oncol 2020;38 East Melbourne, Australia; Fondazione IRCCS Istituto Nazionale dei Tumori and University (11):1154–1163. of Milan, Milan, Italy; 6Antwerp University Hospital, Edegem, Belgium; 7Stanford University, 8 9 Stanford, CA, USA; National Cancer Center Hospital, Kashiwa, Japan; Université http://dx.doi.org/10.1136/jitc-2020-SITC2020.0351 catholique de Louvain, Brussels, Belgium; 10Eisai Inc., Woodcliff Lake, NJ, USA; 11Merck and http://jitc.bmj.com/ Co., Inc., Kenilworth, NJ, USA; 12Yale Cancer Center, New Haven, CT, USA

Background Pembrolizumab alone and in combination with 352 UPDATED CLINICAL DATA FROM THE SQUAMOUS CELL platinum-based chemotherapy have become standard first-line CARCINOMA OF THE HEAD AND NECK (SCCHN) treatment options for recurrent/metastatic head and neck squa- EXPANSION COHORT OF AN ONGOING PH1/1B STUDY mous cell carcinoma (R/M HNSCC), and there is a growing

OF EGANELISIB (FORMERLY IPI-549) IN COMBINATION on September 28, 2021 by guest. Protected unmet need for safe and efficacious treatment options for R/ WITH NIVOLUMAB M HNSCC that has progressed on or after platinum-based chemotherapy and immunotherapy. Data from Study 111/KEY- 1Ezra Cohen*, 2Michael Postow, 3Ryan Sullivan, 4David Hong, 5Heather Yeckes-Rodin, 6 6 7 6 6 NOTE-146 showed promising antitumor activity and accept- Jerry McCarter, Nora Zizlsperger, Jeffery Kutok, Brenda O’Connell, Kara Page, 6Jennifer Roberts, 6Halle Zhang, 8Bartosz Chmielowski. 1University of California San Diego, able safety for the PD-1 inhibitor pembrolizumab given in 2 combination with the multikinase inhibitor lenvatinib in La Jolla, CA, USA; Memorial Sloan Kettering Cancer Center, New York, NY, USA; 3Massachusetts General Hospital, Boston, MA, USA; 4MD Anderson Cancer Center, patients with metastatic HNSCC.1 LEAP-009 (NCT04428151), Houston, TX, USA; 5Heme-Onc Associates of Treasure Coast, Port St. Lucie, FL, USA; a global, randomized, open-label, phase 2 trial, will assess the 6Infinity Pharmaceuticals, Cambridge, MA, USA; 7Epizyme, Cambridge, MA, USA; efficacy and safety of pembrolizumab in combination with len- 8University of California Los Angeles, Los Angeles, CA, USA vatinib versus SOC chemotherapy, as well as the efficacy and safety of lenvatinib monotherapy, in patients with R/M Background Eganelisib is a first-in-class, oral, selective PI3K-g HNSCC that has progressed after platinum-based chemother- inhibitor. Preclinically, eganelisib reprograms macrophages/mye- apy and a PD-(L)1 inhibitor. loid derived suppressor cells (MDSCs) from an immune-sup- Methods Eligible patients are adults with histologically con- pressive to an immune-activating phenotype and enhances firmed, locally incurable R/M HNSCC of the oral cavity, oro- efficacy of checkpoint inhibitors. Efficacy of eganelisib + nivo- pharynx, hypopharynx, or larynx, disease progression at any lumab in patients with SCCHN resistant to immediate prior time during or after platinum-containing chemotherapy (with anti-PD(L)1 therapy is presented.

A214 J Immunother Cancer 2020;8(Suppl 3):A1–A559 Abstracts J Immunother Cancer: first published as 10.1136/jitc-2020-SITC2020.0352 on 10 December 2020. Downloaded from

Methods IPI-549-01 (NCT02637531) evaluates eganelisib in advanced solid tumors, as monotherapy and in combination with nivolumab. The combination expansion dose was eganeli- sib 40 mg QD PO + nivolumab 240 mg Q2W IV. Combina- tion expansion cohorts include SCCHN patients resistant to immediate prior anti-PD(L)1 therapy. Safety, preliminary clini- cal activity, PK, and correlative study of blood and tumor biopsy samples were mandated. Results As of June 1, 2020, 180 patients were treated with eganelisib + nivolumab including 21 with SCCHN.The most common (>20% of patients) treatment-emergent adverse Abstract 353 Figure 1 Iovance LN-145 (autologous TIL cell therapy events in patients treated with eganelisib + nivolumab (N = product) Manufacturing 180) were fatigue (34.4%), increased AST (30.0%), increased ALT (26.7%), nausea (25.0%), pyrexia (25.0%), anemia (22.8%), decreased appetite (20.6%), and cough (20.6%). 85 (47.2%) patients experienced at least 1 treatment-emergent serious adverse event (SAE) and 19 (10.6%) had a treatment- related SAE. There were no treatment-related grade 5 adverse events as assessed by investigators. Preliminary data from the SCCHN cohort show that in the efficacy-evaluable population which includes all patients (n=20) who had at least 1 post- baseline response assessment or discontinued treatment due to disease progression, the overall response rate (ORR, ie. CR Abstract 353 Figure 2 IOV-COM-202 Study Schema [complete response] or PR [partial response] per RECIST v1.1) is 10.0%, the disease control rate (DCR, ie. CR, PR, or SD [stable disease]) is 45.0%, and the clinical benefit rate malignancies alone or in combination with CPI. To improve (CBR, ie. CR, PR, or SD of at least 24 weeks from first treat- HNSCC therapy, a combination of pembrolizumab and LN- ment) is 25.0%, per RECISTv1.1. For patients that received £ 145 was explored. 2 lines of prior systemic therapy (n=11), the ORR is 20.0%, Methods IOV-COM-202 is an ongoing Phase 2 multicenter, the DCR is 40.0%, and the CBR is 30.0%. In total, there are multi-cohort, open-label study evaluating LN-145 in multiple copyright. 2 patients with PR (duration of response 1.6–9.3 months) and settings and indications, and here we report cohort 2A which 3 with SD for greater than 6 months‘ treatment duration. enrolled CPI naïve HNSCC patients who received the combi- Translational data including T cell proliferation in peripheral nation of LN-145 and pembrolizumab. Key eligibility criteria blood as well as markers of inflammation in baseline biopsy include up to 3 lines of prior therapy, ECOG <1, at least of PR patient will be presented. one resectable metastasis for LN-145 production, and at least Conclusions Eganelisib + nivolumab demonstrates an accept- another measurable lesion after tumor resection. Primary end- able safety profile and preliminary clinical activity in patients points are ORR per RECIST v1.1 by investigator and safety with SCCHN who were resistant to immediate prior anti-PD as measured by the incidence of grade 3 treatment-emer- (L)1 therapy. Updated clinical and translational data will be gent adverse events (TEAEs). LN-145 production method uses presented. central GMP manufacturing in a 22-day process yielding a

Ethics Approval The study was approved by WIRB, Study cryopreserved TIL product (figure 1). Preconditioning chemo- http://jitc.bmj.com/ Number 1188591 and IRB Tracking Number: 20180297. therapy consists of /, followed by LN-145, and then < 6 doses of IL-2 over <3 days. Pembroli- http://dx.doi.org/10.1136/jitc-2020-SITC2020.0352 zumab is initiated post-tumor harvest but prior to LN-145 and continues after LN-145 infusion Q3W until toxicity or progression (figure 2). 353 SAFETY AND EFFICACY OF TUMOR INFILTRATING Results Nine (N=9) HNSCC patients have received LN-145 LYMPHOCYTES (TIL, LN-145) IN COMBINATION WITH plus pembrolizumab, with a median duration of follow up on September 28, 2021 by guest. Protected PEMBROLIZUMAB FOR ADVANCED, RECURRENT OR of 6.9 months. Nine and 8 patients were evaluable for METASTATIC HNSCC safety and efficacy, respectively. Mean number of prior 1Antonio Jimeno*, 2Sophie Papa, 3Missak Haigentz, 4Juan Rodríguez-Moreno, therapies was 1.1 with 89% of the patients having received 5Julian Schardt, 6Maria Fardis, 6Friedrich Graf Finckenstein, 6Rana Fiaz, 6Guang Chen, prior chemotherapy. Four were HPV+, 2 HPV-, 3 6Alex Cacovean, 7Zelanna Goldberg, 8Ammar Sukari. 1University of Colorado Cancer Center, unknown. The Treatment Emergent Adverse Event (TEAE) Aurora, CO, USA; 2Guy’s and St Thomas’ NHS Foundation Trus, London, UK; 3Atlantic profile was consistent with the underlying advanced disease 4 Health Systems – Morristown, Morristown, NJ, USA; Hospital Universitario HM and the known AE profiles of pembrolizumab, the lympho- Sanchinarro, Sanchinarro, Spain; 5Universitätsspital Bern, Bern, Switzerland; 6Iovance 7 depletion and IL-2 regimens. The most common TEAE were Biotherapeutics, Inc., San Carlos, CA, USA; Iovance Biotherapeutics, San Carlos, CA, USA; chills, hypotension, anemia, thrombocytopenia, pyrexia, 8Karmanos Cancer Center, Detroit, MI, USA fatigue and tachycardia. Four patients had a confirmed, Background Single agent checkpoint inhibitors (CPI) are an objective response with an ORR of 44% (1 CR, 3 PR, 4 approved first or second-line therapy in head and neck squa- SD, 1 NE) per RECIST 1.1. The disease control rate at mous cell carcinoma (HNSCC), but their efficacy is limited. data cutoff was 89% in 9 patients, and 7 of the 8 evaluable Adoptive cell therapy with tumor infiltrating lymphocytes patients (87.5%) had a reduction in target lesions. Median (TIL, LN-145) has demonstrated efficacy in multiple DOR was not reached.

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