P1, N=475, Recruiting, Tesaro, Inc. | Trial completion date: Jul 2025 --> Apr 2027 | Trial primary completion date: Dec 2024 --> Apr 2025

P1/2, N=59, Recruiting, Novartis Pharmaceuticals | N=27 --> 59 | Trial completion date: Apr 2027 --> Aug 2024 | Trial primary completion date: Nov 2024 --> Jul 2024 | Active, not recruiting --> Recruiting

P2, N=70, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2028 --> Feb 2028

P2, N=90, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2026 --> Jul 2024 | Trial primary completion date: Mar 2026 --> Jul 2024

P2, N=90, Recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2025 --> Jun 2024 | Trial primary completion date: Jan 2024 --> Sep 2023

P1/2, N=0, Withdrawn, Novartis Pharmaceuticals | N=63 --> 0 | Not yet recruiting --> Withdrawn

P1, N=475, Recruiting, GlaxoSmithKline

P1/2, N=27, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=59 --> 27

P2, N=20, Recruiting, Massachusetts General Hospital | Not yet recruiting --> Recruiting | Trial completion date: Dec 2022 --> Jan 2026 | Trial primary completion date: Jun 2022 --> Jun 2024

P2, N=66, Recruiting, Meghan Shea | Not yet recruiting --> Recruiting | Initiation date: Jul 2024 --> Mar 2024

P3, N=530, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2027 --> Sep 2024 | Trial primary completion date: Jan 2027 --> Sep 2024

P2, N=66, Not yet recruiting, Meghan Shea

P1, N=16, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

P1, N=58, Active, not recruiting, Tesaro, Inc. | Phase classification: P1b --> P1

The addition of sabatolimab to hypomethylating agents in this study did not result in a significant improvement in complete response rates or progression-free survival. Sabatolimab had a manageable safety in most patients with higher-risk myelodysplastic syndromes. A randomised phase 3 trial is ongoing to assess the potential benefit of sabatolimab plus azacitidine on overall survival in this setting.

Sabatolimab + HMA had a safety profile similar to that reported for HMA alone and demonstrated durable clinical responses in patients with HR/vHR-MDS. These results support the ongoing evaluation of sabatolimab-based combination therapy in MDS, CMML, and acute myeloid leukemia.

P2/3, N=758, Active, not recruiting, GlaxoSmithKline | Recruiting --> Active, not recruiting

Conversely, we observed a down-regulation of metallothionein genes (MT1E, MT1G, MT2A) as well as a collection of transcription factors (NR4A1, FOSL2, JUN, CEBPB, CEBPD), NF-κB inhibitors (NFKBIZ, NFKBIA) and CXCL8 in the post-treatment samples (FDR <0.1). Conclusions Our study provides one of the most comprehensive evaluations of the cellular dynamics of anti-TIM3 immunotherapy in patients to date, allowing for the nomination of novel putative predictive biomarkers of response and identification of potential immunomodulatory mechanisms induced by the combination of sabatolimab with azacitidine in MDS and CMML for further future analysis.

Among 3 MDS with MECOM rearrangement, one patient received azacitidine with investigational drug (sabatolimab/placebo) and achieved complete hematologic response. Chemotherapy should be avoided in this subtype due to non-responsiveness, hypomethylating agent showed benefit and can be considered as a bridging treatment before stem cell transplantation. Novel therapy targeting MECOM gene should be further explored to improve outcomes in this AML subtype.

Treatment-naive pts aged ≥18 years with intermediate (+ ≥5% bone marrow [BM] blasts), high or very high risk MDS by Revised International Prognostic Scoring System were randomized to sabatolimab or placebo added to azacitidine/decitabine (Zeidan AM, et al. We present the first results from a prospective, controlled, randomized study demonstrating the potential prognostic value of MRD for PFS and OS in HR-MDS. Our results demonstrate high NGS concordance between PBMC and BMMC on-treatment samples, indicating that PBMC could represent an alternative for clonal monitoring. Interestingly, more pts treated with sabatolimab + HMA reached MRD negativity while in remission, potentially explaining the longer DoR in pts receiving sabatolimab + HMA vs placebo + HMA.

In adult pts with AML who are in hematological CR with MRD+ after alloSCT, sabatolimab 400 mg and 800 mg monotherapies were well tolerated. Cytopenias occurred at low rates, were generally G1–2 and mostly related to imminent relapse. Importantly, there were no cases of GvHD reported or any immune-related AEs commonly seen with checkpoint inhibitors.

Galectin-9-induced effects on cytotoxicity can be abrogated using the clinical-grade anti-TIM-3 blocking antibody, MBG453...This may be due to higher intratumoral galectin-9 protein expression in HPV+ HNSCC lesions. Conclusions Our data stress the importance and complexity of TIM-3 in the context of NK cells and suggest that targeting the TIM-3/galectin-9 pathway may be a cogent immunotherapeutic strategy to reinvigorate NK cell effector function in HPV+ HNSCC patients.

P1b, N=58, Active, not recruiting, Tesaro, Inc. | Trial completion date: Apr 2023 --> Apr 2024

Approximately 250 pts will be randomized to Ph2 portion with interim analysis planned after ≥18 weeks follow-up; with an additional 500 pts (Arms A–B [n=200 each] and Arm C [n=100]) in Ph3 portion. Funding: GSK (213410, NCT04655976). Previously presented at IASLCWCLC 2021 and submitted to DKK 2022 on behalf of original authors with their permission.

These results identify melanoma-Tim-3 blockade as a mechanism that antagonizes T-cell-Tim-3-directed IO therapeutic efficacy. They further reveal MAPK targeting as a combination strategy for circumventing adverse consequences of unintended melanoma-Tim-3 inhibition.

Our results identify melanoma cellTim-3 blockade as a potential antagonist of T-cell-Tim-3-directed IO therapy. We uncover MAPK targeting as a combination strategy that can circumvent adverse consequences of unintended melanoma-Tim-3 inhibition.

An additional 500 patients (n=200 each in Arms A-B and n=100 in Arm C) may be included in the Phase 3 portion.Funding: GSK (213410). Editorial support provided by Fishawack Indicia Ltd., UK, part of Fishawack Health, and funded by GSK.

P1, N=40, Active, not recruiting, Incyte Corporation | Trial completion date: Feb 2021 --> Sep 2021 | Trial primary completion date: Feb 2021 --> Sep 2021

P1, N=40, Active, not recruiting, Incyte Corporation | Recruiting --> Active, not recruiting