Squamous cell carcinoma of oropharynx (OPSCC), a head and neck squamous cell carcinoma (HNSCC) subtype, exhibits a remarkably high incidence rate in the North-Eastern regions of India. The development of OPSCC is associated with the exposure to smokeless tobacco with or without consumption of alcohol and smoking tobacco. Despite advanced treatment modalities, OPSCC patients still face a dismal prognosis, necessitating a deeper exploration of the underlying molecular characteristics of the disease. While promoter CpG methylation-driven gene expression alterations in OPSCC have been studied, DNA methylation within gene bodies and its biological significance in this cancer subtype remain largely uncharted. This study represents the first endeavour to investigate gene-body specific DNA methylation-driven transcriptome alterations leading to immune response modulation on a genome-wide scale in OPSCC. The genome-wide assay of DNA methylation and RNA-sequencing in paired tumour and adjacent normal tissues, employing high-throughput platforms (Illumina), identified gene-body specific somatic alterations within the DNA methylome that led to transcriptomic changes in OPSCC patients from Meghalaya. Integrative analysis of gene-body specific methylation and transcriptome data unveiled 98 epigenetically repressed and 39 epigenetically overexpressed genes. Major discoveries emerged from this study include deregulation of Tryptophan (Trp) metabolism pathway by the gene-body driven epigenetically modulated (TDO2, KYNU and TPH2) genes along with the conjoint impact of the upregulated IDO1, IDO2. The IFN-γ mediated PD-L1/PD-1, PD-L2/PD-1 interactions and dysregulation of Trp metabolism pathway collectively contributed to the depletion of cytotoxic T cells in OPSCC tissues. Upregulation of multiple chemokines—CCL2, CXCL1, CXCL2 promoting abundant infiltration of mast cell and neutrophils having pro-tumour phenotype in tumour microenvironment were observed. These key alterations within tumour cells might effectively modulate the immune dynamics, leading to immune evasion by oropharyngeal malignant cells. The findings offer deep understanding of OPSCC and suggests novel immunotherapeutic targets, for the treatment of this challenging disease.

Oral cancer is one of the significant health challenges globally, with late-stage diagnosis contributing substantially to poor prognosis and limited survival rates. Although tissue biopsy is the current gold standard for diagnosis, its invasive nature and limited sensitivity for early lesions restrict its effectiveness in routine screening and longitudinal monitoring. These limitations have driven growing interest in non-invasive molecular approaches that could support earlier detection and more effective clinical monitoring. Deoxyribonucleic Acid (DNA) methylation, a well-established epigenetic modification involved in gene regulation, has emerged as early and consistent events in oral carcinogenesis. Aberrant methylation of Tumour Suppressor Genes (TSG) DNA repairs genes, and other regulatory elements have been consistently reported in Oral Squamous Cell Carcinoma (OSCC). Importantly, these methylation changes can be detected not only in tumour tissue but also in non-invasive oral samples, such as oral brush biopsies and salivary or oral rinse specimens. This narrative review examines the diagnostic and prognostic potential of DNA methylation biomarkers detected through non-invasive sampling methods such as oral brush and salivary rinses. We summarise key findings from existing studies and discuss the relative strengths and limitations of these sampling approaches. Oral brush-based assays generally provide higher sensitivity due to enriched epithelial cell content and lesion-specific signals, whereas salivary and oral rinse-based assays offer greater feasibility for large-scale screening and repeated follow-up. Several multi-gene methylation panels have demonstrated encouraging performance in distinguishing malignant and potentially malignant lesions from normal oral mucosa, as well as in predicting disease recurrence and patient outcomes. Overall, methylation-based assays using oral brush and salivary rinse samples represent promising adjunctive tools for oral cancer detection and monitoring. While further validation, standardisation, and regulatory approval are required before routine clinical implementation, the integration of methylation-based assays into clinical practice holds the potential to significantly advance the early diagnosis and personalised management of oral cancer.

PURPOSE:The phase I, open-label, multicenter AMBER study (NCT02817633) is evaluating cobolimab, an anti-T-cell immunoglobulin and mucin-domain containing protein-3 humanized mAb, as a monotherapy and combination therapy in patients with solid tumors. In this study, the safety and efficacy of cobolimab plus dostarlimab, a PD-1 inhibitor, in patients with locally advanced/metastatic melanoma who were either immunotherapy-naïve or had progressed on prior anti-PD-(L)1 therapy, are reported. PATIENTS AND METHODS:Adults with adequate organ function and either immunotherapy-naïve (parts 1c/1e) or anti-PD-(L)1 relapsed or refractory (part 2A) melanoma were enrolled and received cobolimab 100, 300, or 900 mg and dostarlimab 500 mg every 3 weeks. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent, or death (whichever occurred sooner). Endpoints included safety, tolerability, overall response rate, and disease control rate. RESULTS:The current integrated analysis included 28 patients who received treatment in parts 1c/1e and 43 patients who received treatment in part 2A. Treatment-related serious adverse events were observed in 14.3% and 9.3% of patients in parts 1c/1e and 2A, respectively. The overall response rate (95% confidence interval) was 42.9% (24.5-62.8) and 4.7% (0.6-15.8) for patients in parts 1c/1e and 2A, respectively, and the disease control rate (95% confidence interval) was 53.6% (33.9-72.5; 1c/1e) and 20.9% (10.0-36.0; 2A). CONCLUSIONS:In this exploratory setting, cobolimab plus dostarlimab was well tolerated, with reported preliminary efficacy similar to other anti-T-cell immunoglobulin and mucin-domain containing protein-3 treatments in patients with locally advanced/metastatic melanoma. See related article by Davar et al., p. 3443.

Kaplan–Meier plot of PFS (A) and OS (B) in all patients in part 2A. CI, confidence interval; OS, overall survival; PFS, progression‐free survival; RECIST v1.1, Response Evaluation Criteria for Solid Tumours, version 1.1.

PURPOSE:Treatment options for patients with non-small cell lung cancer (NSCLC) who have progressed on anti-PD-(L)1 treatment are lacking. In preclinical models, blockade of the inhibitory immune receptor T-cell immunoglobulin and mucin-domain containing protein 3 (TIM-3) is associated with an antitumor response. AMBER (NCT02817633) part 2B assessed the safety and efficacy of cobolimab, an anti-TIM-3 humanized monoclonal antibody, plus PD-1 inhibitor dostarlimab in patients with locally advanced or metastatic NSCLC who had progressed on anti-PD-(L)1 treatment. PATIENTS AND METHODS:Adult patients with anti-PD-(L)-1 treated locally advanced or metastatic NSCLC were included. Patients received cobolimab 100, 300, or 900 mg and dostarlimab 500 mg every 3 weeks. Treatment continued until disease progression, unacceptable toxicity, patient withdrawal, investigator's decision, or death. Endpoints included overall response rate, disease control rate, and safety. Post hoc biomarker assessments of pretreatment tumor biopsies were also assessed. RESULTS:In total, 85 patients were enrolled and 84 received treatment. Treatment-emergent and treatment-related adverse events occurred in 98.8% and 52.4% of patients, respectively; no treatment-related deaths occurred. Across all three cobolimab doses, overall response rate was 8.3% (95% confidence interval, 3.4-16.4) and disease control rate was 21.4% (95% confidence interval, 13.2-31.7); both were highest in the 300 mg cohort (n = 41; 9.8% and 22.0%). Pretreatment TIM-3 expression was significantly greater in patients with partial or stable responses versus progressive disease. CONCLUSIONS:Cobolimab plus dostarlimab showed preliminary efficacy and tolerability in a subset of patients with locally advanced/metastatic NSCLC. See related article by Davar et al., p. 3433.

Representativeness of study patients

BACKGROUND:Dual programmed cell death protein (ligand)-1 (PD-[L]1) and lymphocyte-activation gene-3 (LAG-3) blockade has demonstrated improved anti-tumour response in some advanced solid tumours. CITRINO, a two-part, Phase 1 dose-escalation study, evaluated encelimab (TSR-033; novel anti-LAG-3) monotherapy and in combination in patients with advanced/metastatic solid tumours. METHODS:Part 1 (P1) involved dose escalation (20-720 mg Q2W) of encelimab as monotherapy (P1A/B) and with dostarlimab (500 mg Q3W) in patients with previously treated advanced/metastatic solid tumours (P1C). P2 involved cohort expansion in patients with anti-PD-(L)1-naïve microsatellite stable advanced/metastatic colorectal cancer with recommended phase 2 dose (RP2D) of encelimab with dostarlimab as third/fourth-line therapy (P2A), or with dostarlimab, bevacizumab and mFOLFOX6/FOLFIRI as second-line therapy (P2B). Objectives included RP2D, safety/tolerability, efficacy, pharmacokinetics/pharmacodynamics, and exploratory biomarkers. RESULTS:Maximum tolerated encelimab dose was not reached; 720 mg Q2W was used for P2 plus dostarlimab 1000 mg Q6W. One dose-limiting toxicity occurred (Grade 2 myasthenia gravis; P1A). No clinical responses were observed in P1; 1 (3%) and 4 (17%) patients achieved partial response in P2A and 2B, respectively. CONCLUSIONS:Encelimab has a manageable safety profile as a monotherapy and in tested combinations; however, anti-tumour activity was limited. CLINICAL TRIAL REGISTRATION:NCT03250832.

Cancer, a burden upon the global population, has consistently maintained its prevalence throughout history. Gastric cancer compounds this burden and ranks as the fifth leading cause of cancer-related deaths worldwide. The clinical significance of early cancer diagnosis cannot be overstated. DNA methylation biomarkers, a rapidly growing field of liquid biopsy-based diagnostics, provide a minimal to non-invasive way to detect cancer at an early stage. In addition to diagnosis and prognosis, liquid biopsy is important in longitudinal monitoring and therapeutic response prediction, where traditional biopsy faces setbacks. Despite many challenges, DNA methylation being a stable and detectable molecular change attracts the scientific community to develop novel biomarkers and analytical methods to incorporate them into clinical practice. In this review, we have discussed non-invasive, DNA methylation-based gastric cancer biomarkers that have emerged recently. We have also addressed the prognosis and therapeutic response prediction associated with these biomarkers.

Introduction/Background In the phase 3 RUBY trial (NCT03981796) dostarlimab + carboplatin-paclitaxel (CP) significantly improved progression-free survival (PFS) vs CP alone in the mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H; hazard ratio [HR], 0.28) and overall populations (HR, 0.64) with a favourable overall survival (OS) trend (HR, 0.64). Four molecular endometrial cancer subgroups were identified for prognostic and potential predictive value. Readily available validated surrogate methods include POLε mutation (mut), dMMR, TP53 abnormal, and no specific molecular profile (NSMP). Here, we present exploratory efficacy outcomes by molecular classification. Methodology Patients with primary advanced or recurrent endometrial cancer were randomised 1:1 to receive dostarlimab or placebo, plus CP, followed by dostarlimab or placebo monotherapy for up to 3 years. POLε and TP53 status were determined by DNAseq; MMR/MSI status was determined by testing used for study enrolment (immunohistochemistry, polymerase chain reaction, or next-generation sequencing). Order of classification was POLεmut → dMMR/MSI-H → TP53mut → NSMP. PFS and OS were assessed for each subgroup. Results Of 494 patients enrolled and randomised, mutational data were available for 400 patients (81.0%), classified as 5 (1.3%) POLεmut, 91 (22.8%) dMMR/MSI-H, 88 (22.0%) TP53mut, and 216 (54.0%) NSMP. PFS and OS results favoured the dostarlimab + CP arm in the dMMR/MSI-H, TP53mut, and NSMP subgroups, with the largest benefit observed in the dMMR and TP53mut groups. No patients with POLεmut had progression in either arm as of data cut (table 1). Safety was reported previously. Conclusion Dostarlimab + CP is associated with improved PFS and OS in the dMMR/MSI-H, NSMP, and TP53 subgroups and adds prognostic value in primary advanced or recurrent endometrial cancer. Patients with POLεmut had the best prognosis, as expected. Further research may help to validate these exploratory findings. Disclosures Disclosures: This study (NCT03981796) was sponsored by GSK (Waltham, MA, USA). Third-party medical writing support: Writing and editorial support, funded and coordinated by GSK, was provided by Shannon Morgan-Pelosi, PhD, and Mary C. Wiggin, of Ashfield MedComms, an Inizio company. COI: Dr Mirza reports consulting fees from AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zailab; speakers' bureau fees from AstraZeneca and GSK; research funding (to institution) from Apexigen, AstraZeneca, Deciphera (trial chair), GSK, and Ultimovacs; and personal financial interest in Karyopharm (stocks/shares, member of board of directors). Dr Shahin reports institutional grants from AstraZeneca, GSK, and Merck; honoraria from AstraZeneca, GSK, Merck, and Seagen; expert testimony fees from Robinson & Havens PSC, Lexington, KY; advisory board fees from Seagen; and board member for Unite for Her. Dr Cibula reports participation on an advisory board from Akesobio, AstraZeneca, GSK, MSD, Novocure, Roche, Seagen, and Sotio. Dr Raspagliesi reports institutional grants or contracts from AstraZeneca; honoraria from MSD and GSK; travel support from GSK; and advisory board fees from PharmaMar. Dr Hanker reports consulting/advisory fees from Amgen, AstraZeneca, Clovis, Eisai, GSK, Intuitive Surgery, Janssen, MSD, Novartis, Pfizer, Pharma Mar, Roche and Tesaro. Dr Coleman reports grants or contracts from AstraZeneca, Clovis, Genelux, Genmab, Merck, Immunogen, and Roche/Genentech; consulting fees from AbbVie, Agenus, Alkermes, AstraZeneca, Clovis, Deciphera, Genelux, Genmab, GSK, Immunogen, Novocure, Merck, OncoQuest, Onxerna, Regeneron, and Roche/Genentech; honoraria from AstraZeneca, Clovis, Merck, and Roche/Genentech; and participation on a data safety monitoring board or advisory board from Eisai/BMS and VBL Therapeutics. Dr Boere reports institutional research grant from GSK, and institutional advisory board meeting fees from AstraZeneca and GSK. Dr Gilbert reports institutional grants from Alkermes, AstraZeneca, Clovis, Esperas, IMV, ImmunoGen Inc, Karyopharm, Merck Sharp & Dohme, Mersana, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, and Tesaro; consulting fees from Merck; honoraria from Alkermes, AstraZeneca, Eisai, Eisai-Merck, and GSK. Dr Slomovitz reports advisory fees from AstraZeneca, Clovis, Genentech, GSK, GOG Foundation, Merck, Myriad, Jazz Pharma, Onconova, Nuvation Bio, EQRX, Regeneron, Eisai, and Incyte; and board of directors for GOG Foundation and HOW: Hearing Ovarian Cancer Whispers. Dr Powell reports consulting fees from GSK, Tesaro, Merck, Eisai, SeaGen, Clovis Oncology, and AstraZeneca. Dr Stuckey reports royalties as an UptoDate reviewer. Dr Buscema, Dr Fleming, Dr Herrstedt, Dr Ring, Dr Schneider, Dr Sharma, and Dr Teneriello have nothing to declare. Dr Ghosh and Dr Stevens are employees of GSK.

The purpose of this study is to assess the seasonal variation of heavy metal concentration in water and fish tissues of common carp (Cyprinus carpio L.) from the Umiam Lake reservoir located in the Ri bhoi district of Meghalaya, India, and to elucidate the possible human health risk of ingesting fish captured from the contaminated lake. Results show significant (p < 0.05) seasonal differences of heavy metal concentrations in the water and different tissues of fish Cyprinus carpio L.. The total concentration of heavy metals in the water exceeds the WHO and BIS standards and thus poses a significant threat to the aquatic flora and fauna of the reservoir. The heavy metal concentrations in fish tissues were tissue-dependent, where the average concentration of heavy metals in all the tissues of Cyprinus carpio L. was in the order of Cr > Pb > Cu > Cd. In addition, the health risk assessment suggests that the heavy metals in the fish muscle from the Umiam Lake reservoir might have adverse effects on human. Therefore, the overall results of the study provide an understanding on the seasonal distribution of heavy metals in water, provide insight on their bioaccumulation in the fish tissues, and highlights the potential health risk for the local population of long-term fish consumption from Umiam Lake reservoir.

A Bio-Layer Interferometry (BLI)-based method (Forte Bio Octet Red 96) for determining binding rate constants (kon, koff, KD) was utilized to provide kinetic data on the interaction between the monoclonal antibodies (human IgG1 reference standard and TSR-033) and human CD16a

Comparison of mouse and humanized anti-PD-1 and anti-LAG-3 antibodies used in syngeneic and humanized mouse tumor models

TSR-033 binding to LAG-3 by Surface Plasmon Resonance (SPR)

Kaplan-Meier survival curves for huNOG-EXL mice implanted with A549 NSCLC cells treated with isotype control, TSR-042, TSR-033 or TSR-042+TSR-033

Background T-cell immunoglobulin- and mucin-domain-containing-3 (TIM-3) expression on tumor-infiltrating lymphocytes and myeloid-derived cells is associated with immune exhaustion and poor prognosis in patients with NSCLC.1 2 Cobolimab, an anti-TIM-3 monoclonal antibody, in combination with dostarlimab (a PD-1 inhibitor), has been shown to enhance T-cell activity in preclinical assessments.3 Objectives To assess the safety and efficacy of cobolimab plus dostarlimab in patients with advanced/metastatic NSCLC. Methods AMBER (NCT02817633) is a dose escalation and expansion, multicenter, open-label, Phase 1 study assessing cobolimab monotherapy and combinations in patients with advanced solid tumors. AMBER part 2B tested cobolimab and dostarlimab combination in patients with advanced/metastatic NSCLC previously treated with anti-PD(L)-1 therapy. Eligible patients received cobolimab (100, 300, or 900 mg IV) plus dostarlimab (500 mg IV) Q3W. The primary endpoint included objective response rate (ORR) per RECIST v1.1; secondary endpoints included disease control rate (DCR), immune-related (ir)-ORR and irDCR per irRECIST, overall survival (OS), and safety; exploratory endpoints included biomarker assessments (post hoc). Results Eighty-four patients were treated (mean age 65.9 years [range: 35–86]). The most common histologies were adenocarcinoma (69.0%) and squamous cell (26.2%), and 58.3% of patients had ≥3 prior treatment lines. At data cut-off (February 2023), across all doses, ORR was 8.3%, irORR was 9.5%, DCR was 21.4%, and irDCR was 25.0% (table 1). The highest ORR (9.8%) was observed in the cobolimab 300 mg cohort, which was ultimately selected as the recommended Phase 2 dose. Patients with irRECIST defined partial response or stable disease (n=12) had higher baseline TIM-3 immunohistochemistry (research use only assay) levels versus patients with progressive disease (n=22; p=0.013); a similar trend was observed for ORR. Patients with lower than median baseline systemic interleukin (IL)-6 and IL-8 correlated with a higher OS versus patients with higher than median baseline systemic IL-6 and IL-8 (table 2). Treatment-emergent adverse events (TEAEs) ≥1 occurred in 98.8% of patients, most commonly: fatigue (42.9%), dyspnea (31.0%), and decreased appetite (27.4%); 54.8% of patients had Grade ≥3 TEAEs. In total, 52.4%, 13.1%, and 7.1% of patients had treatment-related adverse events (TRAEs), Grade ≥3 TRAEs, and serious TRAEs respectively; no TRAEs deaths were observed. Conclusions Cobolimab plus dostarlimab showed early evidence of efficacy and acceptable safety in patients with advanced/metastatic NSCLC. Cobolimab plus dostarlimab and docetaxel versus standard of care is being evaluated in COSTAR, an ongoing Phase 2/3 study (NCT04655976) for patients with advanced NSCLC. Acknowledgements The authors would like to thank the patients and their families for consenting to the study and analysis, the study coordinators and operations team in facilitating the study, and acknowledge Hasan H Jamal at GSK for their review and coordination of the abstract. Medical writing support was provided by Nicholas Thomas, at Fishawack Indicia, UK, part of Fishawack Health Ltd, and funded by GSK (213348; NCT02817633).. Trial Registration NCT02817633 References Das M,Zhu C, Kuchroo VK. Tim-3 and its role in regulating anti-tumor immunity. Immunol Rev. 2017; 276(1): 97–111. Zhang C, Xu L, Ma Y, Zhou L, Le H, Chen Z. Increased TIM-3 expression in tumour-associated macrophages predicts a poorer prognosis in non-small cell lung cancer: a retrospective cohort study. J Thoracic Disease. 2023; 15(3): 1433–1444. Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med. 2010; 207(10): 2187–2194. Ethics Approval The study was approved by respective IRB/IEC/Competent authorities prior to approval (GSK study 213348).

Profiling of human T, myeloid and NK cells in the spleens of HuNOG-EXL mice (n=3) at day 10 post-inoculation with the A549 cell line

TSR-033 shows little to no binding to C1q by ELISA relative to a human IgG1 reference standard

New strategies for hapten design have led to antibodies that catalyze reactions by increasingly complex mechanisms and with large increases in catalytic rate. Rational design has also been used to elicit catalytic antibodies for difficult chemical transformations as well as reactions for which no enzyme is known. These experiments have demonstrated the chemical potential of large combinatorial libraries that have been given appropriate mechanistic instruction.

2504 Background: TIM-3 expressed on tumor-infiltrating T cells is associated with T-cell suppression. AMBER (NCT02817633) is evaluating cobolimab (TSR-022/GSK4069889) monotherapy and with PD-1 inhibitors in advanced solid tumors. Methods: Multi-center, open-label study conducted with the following escalation arm (Parts 1A–C primary analysis reported here): (1A) cobolimab (IV Q2W) monotherapy at 7 doses (6 weight-based [0.03–10 mg/kg] and 1 flat [1200 mg] dose); (1B) cobolimab (1 mg/kg) + nivolumab (3 mg/kg IV Q2W); and (1C) cobolimab (100, 300, or 900 mg) + dostarlimab (500 mg IV Q3W). Primary endpoints were safety, tolerability, and recommended phase 2 dose (RP2D, monotherapy and combination). Results: 104 patients (pts) were included: 1A (n=46), 1B (n=7), or 1C (n=55); 4 pts from 1A crossed over to 1C (included in 1A and 1C safety and efficacy analyses). Most common cancers were non-small cell lung cancer (NSCLC) and melanoma (1A), NSCLC (1B), and NSCLC, skin, and peritoneal mesothelioma (1C). In 1A, 30.4% had ≥5 lines (L) of prior therapy; 42.9% had 3L in 1B; 33.3% had 2L in 1C. Treatment-related treatment-emergent adverse events (TR-TEAE) occurred in 67.4% (1A), 85.7% (1B), and 67.3% (1C); most commonly in 1A (n≥4) fatigue (13.0%) and nausea (8.7%); 1B (n≥3) diarrhea (57.1%) and nausea and vomiting (42.9% each); and 1C (n≥8) fatigue (20.0%) and rash (14.5%). Grade (Gr)≥3 TR-TEAEs occurred in 4.3% (1A), 28.6% (1B), and 14.5% (1C). There were no Gr5 TR-TEAEs or TR-TEAEs leading to dose delay. Serious TR-TEAEs occurred in 2.2% (1A), 0% (1B), and 12.7% (1C). TR-TEAEs led to discontinuation in 2.2% (1A), 28.6% (1B), and 9.0% (1C). Dose limiting toxicities (DLTs) occurred in 3.0% (1/33) in 1A (Gr3 lipase increased [10 mg/kg]); 40.0% (2/5) in 1B (Gr3 diarrhea and ALT and AST elevation); and 0% in 1C. Cobolimab serum exposure increased in a dose proportional manner at the therapeutic dose range. Preliminary mean terminal phase t1/2 ranged from 2.5–5.8 days for 0.03–0.3 mg/kg and 6.9–10.2 days for 1–10 mg/kg doses (1A), 6.9 days for 1B, and 9.5–12.3 days for 1C. Conclusions: Cobolimab + dostarlimab was well tolerated and showed preliminary anti-tumor activity, warranting further investigation of the RP2D + docetaxel in a randomized, phase 2 study. Funding: GSK (213348). Clinical trial information: NCT02817633. [Table: see text]

Treatment of patients with recurrent/advanced NSCLC has been revolutionized by the introduction of ICIs. A Phase I trial of PD-1 inhibitor dostarlimab demonstrated antitumor activity in 67 patients with recurrent/advanced NSCLC, with an irORR of 26.9% (2 complete responses), including across all PD-L1 status subgroups. Dostarlimab had an acceptable safety profile with 11.9% of patients experiencing Grade >= 3 TRAEs. Background: Dostarlimab is an anti-programmed cell death protein-1 antibody being evaluated in recurrent/advanced solid tumors, including non-small cell lung cancer (NSCLC), in the ongoing Phase I, multi-center, open-label, 2-part (dose escalation and cohort expansion) GARNET study (NCT02715284). Materials and Methods: Here, we report an interim analysis of patients with recurrent/advanced NSCLC who progressed following platinum-based chemotherapy. Patients received dostarlimab (500 mg IV every 3 weeks [Q3W] for Cycles 1-4, then 1000 mg Q6W) until disease progression or unacceptable toxicity for >= 2 years. The primary endpoints were immune-related objective response rate (irORR) per investigator-assessed irRECIST and safety. Results: As of 8, July 2019, 67 patients with recurrent/advanced NSCLC were enrolled and treated with dostarlimab; the majority had programmed death ligand 1 (PD-L1) tumor proportion score (TPS) < 1% (35.8% of patients) or PD-L1 TPS 1%-49% (29.9% of patients); 7.5% had PD-L1 TPS >= 50%, and 26.9% had unknown PD-L1 TPS status. Median follow-up was 13.8 months (range: 0.0-22.6). irORR was 26.9%, including 2 complete and 16 partial responses. The median duration of response of 11.6 months (range: 2.8-19.4). Responses were observed in 2 of 24 (16.7%) patients with PD-L1 TPS < 1%, 4 of 20 (20.0%) patients with PD-L1 TPS 1%-49% and 2 of 5 (40.0%) patients with PD-L1 TPS >= 50%. Fatigue (4.5%) was the most common Grade >= 3 treatment-related treatment-emergent adverse event (TRAE). Immune-related TRAEs (any grade) were observed in 28.4% of patients. Conclusion: Dostarlimab demonstrated promising antitumor activity in advanced/recurrent NSCLC that progressed following platinum-based chemotherapy, including across all PD-L1 subgroups, and has an acceptable safety profile.