P2/3, N=849, Active, not recruiting, Immutep S.A.S. | Recruiting --> Active, not recruiting

P3, N=756, Not yet recruiting, Immutep S.A.S.

Table: 152P RECIST 1.1 N=31 iRECIST N=31 Complete response (%) 9.7 9.7 Partial response (%) 25.8 29.0 Stable disease (%) 22.6 25.8 Progressive disease (%) 41.9 35.5 Overall Response Rate (ORR)* (%), [95% CI] 35.5, [19.2-54.6] 38.7, [21.8-57.8] Disease Control Rate (DCR) (%), [95% CI] 58.1, [39.1-75.5] 64.5, [45.4-80.8] *10/11 responses confirmed by RECIST 1.1 and 11/12 by iRECIST.Conclusions E + P leads to high ORR and DCR in a CPS negative pt population, which is typically unresponsive to P alone. Further late-stage clinical investigation is warranted for E+P in this disease setting.

OX40L-CAR-Tregs demonstrated an enhanced ability to control xenogeneic graft-versus-host disease compared with control Tregs without abolishing the graft-versus-leukemia effect. These results suggest that OX40L-CAR-Tregs may have wide applicability as a potent cellular therapy to control both allo- and autoimmune diseases.

Efti plus pembrolizumab was well-tolerated and revealed signs of antitumor activity in patients with NSCLC resistant to PD-(L)1 inhibitors, warranting further investigation. Trial registration number: NCT03625323.

E+P is well tolerated with positive efficacy data and should be investigated further in HNSCC.

Efti plus pembrolizumab was safe and showed encouraging antitumor activity and pharmacodynamic effects in 2nd line HNSCC patients, thus supporting further evaluation of this combination in earlier treatment lines.

Differentially expressed genes were found to be enriched in antigen processing process, specifically increased tumor infiltration of DCs, B1 cells and plasma cells in the OVA plus GFPBW1 group, in accordance with its activation and maturation function of APCs. Collectively, this study systematically describes the properties of GFPBW1 as a novel potent and safe adjuvant and highlights its great potential in vaccine development.

P2; N=171; Active, not recruiting; Sponsor:Immutep S.A.S.

P2, N=40, Recruiting, Maria Sklodowska-Curie National Research Institute of Oncology

P2; Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2023 --> Mar 2024

Although the primary endpoint, PFS, was not met, AIPAC confirmed expected pharmacodynamic effects and demonstrated excellent safety profile for efti. Overall survival was not significantly improved globally (2.9-month difference), but was significantly improved in exploratory biomarker subgroups, warranting further studies to clarify efti's role in patients with ET-resistant HER2- MBC.

No abstract available

Subcutaneously administered efti plus avelumab was well tolerated, and efti of 30 mg was determined to be RP2D. The activity is promising and warrants further investigation in future phase II trials.

P2, N=189, Active, not recruiting, Immutep S.A.S. | Trial completion date: Nov 2023 --> Nov 2024

GEP analysis showed upregulated expression of genes related to T-cell functions, cytotoxicity functions, cytotoxic cells, or TH1 cells which are more pronounced in pts with PR/CR. Conclusions Significant early and sustained increases of circulating biomarkers and ALC substantiate the systemic stimulation via the APC activator efti and show that repeated minimally-invasive liquid biopsies, i. e. , blood samplings, are key in detecting this systemic stimulation.

Not applicable

P1, N=110, Recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | N=45 --> 110 | Trial completion date: Jun 2024 --> Sep 2025 | Trial primary completion date: Jun 2024 --> Sep 2025

P2; Trial primary completion date: Jul 2023 --> Dec 2023

To date, two LAG-3-directed agents (eftilagimod alpha and relatlimab) have been approved in combination with programmed death-1 (PD-1) inhibitors in the setting of advanced solid tumors. In this review, we discuss the structure of LAG-3, its mechanism of action, and its interaction with its ligands. We also shed light on the emerging treatments targeting LAG-3 for the treatment of solid tumors.

Correlation between tissue or blood-based biomarkers and clinical outcomes will be explored. Enrollment for the study is ongoing in Poland.

Methods Pts with 1st line advanced or metastatic NSCLC adenocarcinomas (non-squamous) receive carboplatin AUC5 / pemetrexed 500 mg/m2 q3w 4 cycles followed by optional pemetrexed 500 mg/m2 q3w maintenance plus pembrolizumab 200 mg q3w combined with s.c. efti (30 mg) (q2w for 24 weeks; thereafter q3w till week 52). Median follow up: 8.3 months, median OS: not reached. Conclusions To date, 30 mg efti combined with SOC appears to be feasible and safe with promising signals of efficacy, so that the trial was amended for inclusion of further 30 pts.

Conclusions E + P shows encouraging OS results in line with excellent ORR, PFS and DOR in 1st line NSCLC overall and in all PD-L1 subgroups. This combination warrants further late-stage clinical investigation.

Sponsored by Pharmaceutical/Biotech Company, Immutep S.A. Clinical Trial Registration Number: NCT03625323. Efti + pembrolizumab is safe, showing encouraging antitumor activity in platinum and partially cetuximab pre-treated, 2nd line HNSCC patients. TACTI-003 (NCT04811027) a randomized study in 1st line HNSCC is currently recruiting. Response by iRECIST: Clinical trial information: NCT03625323.

Key inclusion criteria: Pts with either a) HR+ and HER2-neg/low and endocrine therapy-resistant MBC or b) TNBC not eligible for anti-PD-1-based therapy. Pts must have measurable disease, ECOG PS 0-1 and no prior chemo for metastatic disease.

Key inclusion criteria: Pts with either a) HR+ and HER2-neg/low and endocrine therapy-resistant MBC or b) TNBC not eligible for anti-PD-1-based therapy. Pts must have measurable disease, ECOG PS 0-1 and no prior chemo for metastatic disease.

P1, N=0, Withdrawn, Immutep S.A.S. | N=24 --> 0 | Not yet recruiting --> Withdrawn

P2/3, N=849, Recruiting, Immutep S.A.S. | Not yet recruiting --> Recruiting

The remaining 50% of metastasizing SCTs were CTNNB1-wild-type and harbored alterations in TP53, MDM2, CDKN2A/CDKN2B, and TERT pathways. These findings suggest that aggressive SCTs can arise from progression of CTNNB1-mutant benign SCTs, or from CTNNB1-wild type tumors with alterations of TP53, cell cycle regulation, and telomere maintenance pathways.

Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system...Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.

The usage of these substances in the treatment of solid tumors is being investigated. The present review discusses the direct and indirect influence that TLR7/8 agonists, such as imiquimod, imidazoquinolines and resiquimod have on neoplastic cells and their promising role as adjuvants in anticancer vaccines.

P2/3, N=849, Not yet recruiting, Immutep S.A.S.

Most common (>15%) adverse events were decreased appetite (33%), dyspnea (31%), cough (28%), asthenia (22%), fatigue (19%), arthralgia (17%) and weight decreased (17%). Conclusions Efti + pembrolizumab is safe and shows encouraging signs of antitumor activity in NSCLC pts resistant to PD-1/PD-L1 inhibitors, warranting further investigation.

In SPOPMT PCs, inactivation of APC is a common event and associated with more aggressive disease (higher metastatic potential and faster progression to castration resistance). This observation may help identify SPOPMT PC patients who are at higher risk for early castration resistance and could benefit from more intensive treatment.

Sotiga induced dramatic changes in the tumor microenvironment including increased frequency of activated T cells and APCs, and decreased frequency of Tregs. A distinct signature of T cell infiltration in baseline tumor biopsies was observed in patients who achieved a pCR versus those who did not, potentially identifying patients that may benefit from this novel treatment strategy.

30 mg efti appears to be feasible and safe.

Some first-line cytotoxic chemotherapics, e.g. doxorubicin, paclitaxel and oxaliplatin, induce activation of the immune system through immunogenic cell death (ICD). Bona fide ICD induction by CA was confirmed by vaccination of C57BL/6 mice with CA-treated cells which activated antigen-presenting cells and T lymphocytes and stimulated antitumor activity. CA induces bona fide immunogenic cell death on melanoma.

When combined with a PD-1 checkpoint inhibitor, the soluble LAG3 drug eftilagimod alpha activates antigen-presenting cells, offering deep and durable responses against non-small cell lung cancer. Even patients whose tumors express low levels of PD-L1 experienced an anticancer benefit.

Using lipoplex (Lipo-PEG-PEI-complex, LPPC) encapsulated doxorubicin (DOX) and carrying CpG oligodeoxynucleotide; the transdermally administered nano-liposomal drug complex (LPPC-DOX-CpG) would have high cytotoxicity and immunostimulatory activity to suppress systemic metastasis of melanoma...Furthermore, NGS analysis revealed IFN-γ and NF-κB pathways were triggered to recruit and activate the antigen-presenting-cells and effecter cells, which could activate the anti-tumor responses as the major mechanism responsible for the therapeutic effect of LPPC-DOX-CpG. Finally, we have successfully proved transdermal LPPC-DOX-CpG as a promising penetrative carrier to activate systemic anti-tumor immunity against subcutaneous and metastatic tumor.

P2 | "Early & sustained increases of circulating CXCL-10 & IFN-gamma levels were observed. Conclusions E + P is safe & shows encouraging antitumor activity in 1st line metastatic NSCLC patients unselected for PD-L1, warranting late-stage clinical investigation."

The QFN-PTT-treated mice exhibited significantly elongated survival time, and gained strong anti-tumor immune memory to prevent tumor metastasis and recurrence. Thus, this work provided a simple and versatile photothermic agent, and it has important implications for designing effective and translationally feasible photosensitizers for PTT.