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Nov 19, 2024
The Society for Immunotherapy of Cancer i.e., SITC 2024 conference provided a comprehensive view into the latest innovations in cancer immunotherapy, including data on CAR T-cell therapies, cancer vaccines, bispecific and multispecific antibodies, along with next-generation cancer vaccines. Presentations from various pharmaceutical companies such as GlaxoSmithKline, Elicio Therapeutics, Palleon Pharmaceuticals, Novocure, Sapience Therapeutics, HUYABIO International, IO Biotech, Luminary Therapeutics, Innate Pharma, Nimbus Therapeutics, Immunomic Therapeutics, Agenus, Elicio Therapeutics, Oncotelic Therapeutics, Infinitopes, Xenetic Biosciences, Poseida Therapeutics and many others, emphasized the ongoing shift towards more personalized and targeted therapeutic approaches.
Checkpoint inhibitors continue to be a high-stakes area, with companies aiming to differentiate through next-generation molecules and novel combination regimens. This market sees major competition among Merck, Bristol-Myers Squibb, and now newer entrants like Palleon aims to capture niche patient segments with resistance to PD-(L) 1 therapies, Elicio Therapeutics revealsdata of its cancer vaccine in high relapse risk KRAS mutated pancreatic ductal adenocarcinoma and colorectal cancer, Marengo’s promising first-in-Human data for its Lead Program, Invikafusp Alfa, TCR β chain-targeted bispecific antibody. Innate Pharma came up with its proprietary next generation antibody-drug conjugate (ADC) and innovative tetra-specific ANKET.
In addition, for patients with advanced NSCLC, the results from the PERLA trial bring encouraging news. Currently, KEYTRUDA has dominated the NSCLC therapeutic landscape and has been a major revenue driver for Merck. However, as KEYTRUDA’s patent is near its expiration in 2028, the market anticipates increased competition. The favorable outcomes observed with dostarlimab in the PERLA trial position it as a potential competitor in the NSCLC market. In the trial, patients receiving the combination of dostarlimab and chemotherapy achieved a median overall survival of 20.2 months, noticeably longer than the 17.5 months observed in the pembrolizumab arm, potentially establishing dostarlimab as a preferred first-line treatment option. These developments will likely drive continued innovation, as companies vie to establish dominance in the immunotherapy field for lung cancer.
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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 2024 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 pharma and biotech industry. The rise of 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 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. 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. Top-abstracts presented during the meeting have been summarized in the table below:
List of few top-abstracts presented at 2024 STIC Annual Meeting | |||||
Drug Name | Company Name | Abstract Number | Tittle | Patient Segment | Results |
Dostarlimab + chemotherapy | GlaxoSmithKline | 711 | 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) | Metastatic non-squamous non-small cell lung cancer (NSCLC) | Median OS was 20.2 months in the dostarlimab + CT arm vs 15.9 months in the pembrolizumab + CT armNo new safety signals were reported. |
E-602 + cemiplimab | Palleon Pharmaceuticals | 758 | 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 | PD-(L)1-resistant solid tumors | 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. |
TTFields Plus Temozolomide/Pembrolizumab | Novocure | 591 | 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 | Glioblastoma | 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%). |
ST101 | Sapience Therapeutics | 991 | 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) | Gliolastoma | 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. |
HBI-8000 | HUYABIO International | 620 | HBI-8000, a class I histone deacetylase (HDAC) inhibitor, in combination with nivolumab for treatment of anti- PD(L)1-naive advanced melanoma: final analysis of study HBI-8000–302 | PD(L)1-naive advanced melanoma | Overall response rate was 65.8%, Clinical benefit rate was 87%.Median progression-free survival was 36.9 monthsMedian duration of response was not reached.Seventeen patients discontinued treatment due to AEs. |
IO102-IO103 + pembrolizumab | IO Biotech | 756 | 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) | Metastatic non-small cell lung cancer (NSCLC) | 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. |
LMY-920 | Luminary Therapeutics | 244 | A phase 1 study of novel transposon-based BAFF CAR-T cells (LMY-920) for treatment of relapsed or refractory non-hodgkin lymphoma (NHL) | Relapsed or refractory non-hodgkin lymphoma (NHL) | 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 have been no dose limiting toxicities and dose escalation continues. |
IMA203 | Immatics | 687 | ACTengine IMA203 TCR-T targeting PRAME shows deep and durable anti-tumor activity in heavily pretreated solid cancer patients | Solid tumor | 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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Nov 20, 2024
Nov 19, 2024