ImmuFact (eftilagimod alpha)

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.

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

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.

30 mg efti appears to be feasible and safe.

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.

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."

Secondary EPs include overall survival, ORR according to iRECIST, time to and duration of response, disease control rate, progression-free survival, the occurrence of anti-efti -specific antibodies, safety, and quality of life. Exploratory endpoints comprise biomarkers.

P1, N=24, Not yet recruiting, Immutep S.A.S. | Trial completion date: Feb 2024 --> Feb 2026 | Trial primary completion date: Jun 2023 --> Jun 2025

Efti in combination with pembrolizumab is safe and shows encouraging signs of antitumor activity in truly PD-1/PD-L1 refractory 2nd line NSCLC pts.

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

E + P is safe and shows encouraging antitumor activity in first-line metastatic NSCLC patients unselected for PD-L1, warranting further investigation.

Exploratory endpoints comprise biomarkers. The study has been approved by relevant competent authorities, ethic committees and IRBs.

P2, N=50, Not yet recruiting, Taizhou EOC Pharma Co., Ltd.

P1, N=12, Completed, Taizhou EOC Pharma Co., Ltd. | Recruiting --> Completed | N=18 --> 12 | Trial completion date: Sep 2020 --> Dec 2021 | Trial primary completion date: Aug 2019 --> Dec 2021

IMP321 and relatlimab are promising monoclonal antibodies targeting LAG3 in melanoma. Finally, high FGL1 and LAG3 expression induces EGFR-TKI and gefitinib resistance, and anti-PD-1 therapy resistance, respectively. We present a comprehensive overview of the role of LAG3/FGL1 in cancer, suggesting novel anti-tumor therapy strategies.

Both responses were reported in pts pre-treated with chemo + PD-1 and under therapy since 7+ and 12+ months at data cut-off. Conclusions Efti in combination with pembrolizumab is safe and shows encouraging signs of antitumor activity in PD-1 refractory 2 nd line NSCLC pts.

P2, N=189, Active, not recruiting, Immutep S.A.S. | Recruiting --> Active, not recruiting

Weekly paclitaxel + efti should be further investigated in MBC. Trial Registration The trial identifiers are IMP321-P011 (code for sponsor), 2015-002541-63 (EudraCT) and NCT02614833 (ClinicalTrials.gov).

P2; Not yet recruiting --> Recruiting | Trial primary completion date: Apr 2023 --> Jul 2023

Combined treatment with avelumab 800mg and efti 6mg (coh 1) or efti 30mg (coh 2) was well tolerated with no unexpected AEs observed. No unexpected AEs occurred. Signals of efficacy with immune checkpoint inhibition (CPI) combination were seen (disease control rate of 50%).

P2b, N=242, Completed, Immutep S.A.S. | Active, not recruiting --> Completed

The study has been approved by relevant competent authorities, ethic committees and IRBs. Trial Registration NCT04811027

For further investigation of this combination, a 1st line HNSCC trial (NCT04811027) has been initiated. Trial Registration NCT03625323