Abstract CT056: Durable complete responses to adoptive cell transfer using tumor infiltrating lymphocytes (TIL) in non-small cell lung cancer (NSCLC): A phase I trial
Authors: Creelan Ben , Wang Chao , Teer Jamie , Toloza Eric , Mullinax John , Yao Jiqiang , Koomen John , Kim Sungjune , Chiappori Alberto , Saller James , Montoya Leighann , Landin Ana Marie , Tanvetyanon Tawee , Fang Bin , Thompson Zachary , Yu Xiaoping , Saltos Andreas , Chen Dung-Tsa , Conejo-Garcia Jose , Haura Eric , Antonia Scott 
Published: September 2020

Abstract
Study Objectives: A hallmark of tumor infiltrating lymphocytes (TIL) in melanoma is the potential for a complete response (CR) which can last for decades. This long-lived effect is attributed to persistence of memory T cells. However, clinical efficacy in metastatic non-small cell lung cancer (mNSCLC) has not previously been reported. We launched a phase I trial with the objective to evaluate the safety and efficacy in mNSCLC after evidence of progression on nivolumab.
Methodology: Full eligibility criteria is described in trial registry (NCT03215810). Patients were required to have mNSCLC with at least 1 RECIST measurable lesion and also 1 lesion safely accessible for excisional biopsy, usually a supraclavicular lymph node or pleural nodule. This histologically confirmed metastasis was resected and TIL cultured. Autologously reactive cultures were pooled and cryopreserved. TIL was successfully expanded in 95% of patients, to a median dose of 103 billion CD3+ cells. Patients received nivolumab for 4 cycles with two serial CT scans. Patients with tumor enlargement or new lesions proceeded to lymphodepletion cyclophosphamide/fludarabine (Cy/Flu), TIL, and attenuated IL-2. After first CT scan, patients resumed nivolumab for up to 11 doses to augment TIL persistence.
Results: Of 32 patients screened, 20 were eligible and enrolled. Median age 54 yrs (range 38 - 75), median PD-L1 proportion score 6%, median estimated TMB 5 mut/MB, 20% EGFR-mutant. The majority had bulky disease with mean sum of target lesion diameters of 7.0 cm. Of 20 enrolled, 13 had evidence of progression on nivolumab and received subsequent Cy/Flu/TIL/IL-2. Two more are progressing on nivolumab and set to receive TIL within next 2 months. Common non-hematologic adverse events (AEs) of the Cy/Flu/TIL/IL2 regimen included hypoalbuminemia (92%), hypophosphatemia (85%), nausea (77%), hyponatremia (69%), diarrhea (62%), the majority of these AEs resolving by Day +10 post-TIL. Initial tumor regression occurred in most patients at their first post-TIL CT scan, with the median best overall change in sum of target lesion diameters of -38% (range +20 to -100). Median time-on-trial post-TIL is 1.4 years. Two patients have achieved durable CRs which are still ongoing almost 1 year post-TIL. One is a never-smoker with EGFREx19 mutation and PD-L1 1%. Three additional patients were able to maintain a clinical remission by local ablative therapy of an isolated new lesion performed 6 to 17 months post-TIL. Persistence of the infused TCR-Vβ clonotypes at post-infusion timepoints was associated with clinical benefit. Neoantigen-specific T cells were detected in the TIL and post-TIL peripheral blood.
Conclusions: TIL has manageable toxicity and capacity to achieve durable remission in mNSCLC after nivolumab treatment. TIL may be a promising option for fit mNSCLC patients.
Citation Format: Ben Creelan, Chao Wang, Jamie Teer, Eric Toloza, John Mullinax, Jiqiang Yao, John Koomen, Sungjune Kim, Alberto Chiappori, James Saller, Leighann Montoya, Ana Marie Landin, Tawee Tanvetyanon, Bin Fang, Zachary Thompson, Xiaoping Yu, Andreas Saltos, Dung-Tsa Chen, Jose Conejo-Garcia, Eric Haura, Scott Antonia. Durable complete responses to adoptive cell transfer using tumor infiltrating lymphocytes (TIL) in non-small cell lung cancer (NSCLC): A phase I trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT056.