Targeting the TME (Tumor Microenvironment) represents a new front in immunotherapy, with Novocure leading the charge alongside other companies exploring macrophage modulation and Treg targeting. Novocure’s Tumor Treating Fields (TTFields) technology, combined with pembrolizumab, demonstrated impressive survival benefits in glioblastoma by creating an “in-situ vaccination” effect within the TME. This approach signals a new strategy to make otherwise immune-resistant tumors more accessible to immune responses.
Late-breaking abstracts at the SITC conference showcased not only promising results but also data from failed trials. Among these were Merck’s anti-TIGIT monoclonal antibody, vibostolimab, from the failed KEYVIBE-008 study, which was featured as an oral presentation, and Arcus Biosciences and Gilead Sciences‘ anti-TIGIT mAb, domvanalimab, whose discontinued ARC-10 trial was presented as a poster. Despite their setbacks, these trials provide critical insights into the challenges and opportunities in targeting TIGIT, a pathway still considered promising for combination immunotherapy approaches.
Among other notable antibody-focused approaches, the conference included presentations highlighting advancements in CCR8 blockade and Claudin18.2 bispecifics, both of which remain hot areas of interest in the pharma and biotech industry. The rise of the CCR8 blockade has been low-key, but it has seen buy-in from major players like Amgen, Roche, AbbVie, and Bristol Myers Squibb. The conference showcased results from a Phase I study of QLP2117, a CCR8-targeting mAb developed by China’s Qilu Pharmaceutical, in solid tumors.
Claudin18.2 blockade, continues to draw significant attention, and is now validated by Astellas’s recent approval of VYLOY (zolbetuximab-clzb) in Gastric Cancer, continues to draw significant attention. Data on Q-1802, a Claudin18.2 x PD-L1 bispecific from QureBio, and givastomig, I-Mab’s Claudin18.2 x 4-1BB co-stimulated approach were presented at the conference.
The CAR T-cell market is currently dominated by hematologic cancers, but data presented at the conference from various pharmaceutical companies reflects opportunities for CAR T-cells in solid tumors. A few of the notable examples include Fate Therapeutics’ FT825/ONO-8250, an off-the-shelf, iPSC-derived CAR T-cell therapy candidate, for treating advanced solid tumors; Cellectis, which shared preclinical findings on enhancing CAR T-cell efficacy in solid tumors while reducing toxicity, whereas Poseida Therapeutics presented data on its Allogeneic CAR-T Cell Therapies.
Looking forward, it seems like, combination therapies and biomarker-driven approaches will dominate the next wave of immunotherapy. The top abstracts presented during the meeting have been summarized in the table below:
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List of a few top abstracts presented at the 2024 STIC Annual Meeting
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Drug Name
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Company Name
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Abstract Number
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Title
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Patient Segment
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Results
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Dostarlimab + chemotherapy
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GlaxoSmithKline
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711
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Updated overall survival from PERLA, a phase II randomized double-blind trial of dostarlimab + chemotherapy (CT) vs pembrolizumab + CT in metastatic non-squamous non-small cell lung cancer (NSCLC)
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Metastatic non-squamous non-small cell lung cancer (NSCLC)
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– Median OS was 20.2 months in the dostarlimab + CT arm vs 15.9 months in the pembrolizumab + CT arm
– No new safety signals were reported.
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E-602 + cemiplimab
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Palleon Pharmaceuticals
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758
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GLIMMER-01: Phase I/II trial of a first-in-class bi-sialidase (E-602) in combination with cemiplimab in patients with PD-(L)1-resistant solid tumors
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PD-(L)1-resistant solid tumors
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– The most frequent treatment-related AEs were infusion-related reactions
– Partial response (PR) and stable disease (SD) were achieved in 1 and 6 patients, respectively.
– Decreases in tumor infiltrating CD163+ macrophages were evident.
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TTFields Plus Temozolomide/Pembrolizumab
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Novocure
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591
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In-situ vaccination by tumor treating fields and anti-PD-1 immunotherapy in patients with large residual GBM results in robust T cell selection and expansion, high response rate, and extended survival
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Glioblastoma
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– Patients with biopsy-only tumors displayed a marked improvement in both progression-free survival (27.2 m), overall survival (31.6 m) and response rates (66.6%).
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ST101
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Sapience Therapeutics
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991
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ST101, an inhibitor of the transcription factor C/EBPß, promotes an immune-active tumor microenvironment in a window of opportunity (WoO) study of patients with glioblastoma (GBM)
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Gliolastoma
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– 4/6 rGBM patients show DC and 50% 6-month PFS, and 5/6 newly diagnosed GBM patients showed DC.
– Increase in the M1/M2 ratio of TAMs in resected recurrent GBM and newly diagnosed GBM tumors.
– ST101 was safe and well-tolerated with no discontinuations due to AEs.
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HBI-8000
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HUYABIO International
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620
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HBI-8000, a class I histone deacetylase (HDAC) inhibitor, in combination with nivolumab for the treatment of anti-PD (L)1-naive advanced melanoma: final analysis of study HBI-8000–302
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PD(L)1-naive advanced melanoma
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– Overall response rate was 65.8%, Clinical benefit rate was 87%.
– Median progression-free survival was 36.9 months
– Median duration of response was not reached.
– Seventeen patients discontinued treatment due to AEs.
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IO102-IO103 + pembrolizumab
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IO Biotech
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756
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A phase 2 trial of the IO102-IO103 cancer vaccine plus pembrolizumab: results from the first-line (1L) cohort of PD-L1 high metastatic non-small cell lung cancer (NSCLC)
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Metastatic non-small cell lung cancer (NSCLC)
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– Confirmed ORR was 48.4%
– Disease control rate is 80.6%.
– PFS at 6 months was 61%.
– TRAEs of any grade were reported in 29 patients with 9 grade ≥3 and 3 serious events.
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LMY-920
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Luminary Therapeutics
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244
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A phase 1 study of novel transposon-based BAFF CAR-T cells (LMY-920) for treatment of relapsed or refractory non-Hodgkin lymphoma (NHL)
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Relapsed or refractory non-Hodgkin lymphoma (NHL)
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– Disease responses observed included one complete response (DLBCL), partial response (MCL), and stable disease (MCL).
– All patients experienced grade 3 or higher hematologic toxicity.
– There has been no dose-limiting toxicities and dose escalation continues.
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IMA203
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Immatics
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687
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ACTengine IMA203 TCR-T targeting PRAME shows deep and durable anti-tumor activity in heavily pretreated solid cancer patients
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Solid tumor
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– TEAEs were manageable with most common events being chemotherapy-related cytopenias and mainly mild to moderate CRS.
– cORR in patients with melanoma was 58%.
– Median duration of response was 10.5 months.
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