ieramilimab (LAG525) / Novartis, Immutep - LARVOL DELTA

For LAG525, which is exclusively licensed to Novartis by Immutep, a new patent was granted in Taiwan. (The Manila Times)

Patent • Solid Tumor

Targeting LAG-3: Relatlimab, Fianlimab, and ieramilimab reshape the landscape of cancer combination immunotherapy. (PubMed, Pathol Res Pract) - "This review discusses the biology of LAG-3, the pharmacological characteristics of Relatlimab, Fianlimab, and Ieramilimab, as well as their potential synergistic effects when combined with other ICIs. Moreover, it addresses resistance mechanisms, patient selection, and challenges with combination therapies in cancer."

Journal • Review • Melanoma • Oncology • Solid Tumor • LAG3

INTELLECTUAL PROPERTY (GlobeNewswire) - "During the quarter, Immutep was granted seven new patents for efti, IMP761 and LAG525 (ieramilimab) in various territories...Two patents were granted for efti in combination with a PD-1 pathway inhibitor in South Korea and Brazil and one patent was granted in Mexico for a binding assay for determining MHC Class II binding activity...New patents were also granted for IMP761 in India and Israel. For LAG525, which is exclusively licensed to Novartis by Immutep, two new patents were granted in Australia and Taiwan."

Patent • Breast Cancer • Colorectal Cancer • Inflammatory Bowel Disease • Melanoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Ovarian Cancer • Prostate Cancer • Rheumatoid Arthritis

A phase 2, multicenter, open-label study of anti-LAG-3 ieramilimab in combination with anti-PD-1 spartalizumab in patients with advanced solid malignancies. (PubMed, Oncoimmunology) - "Biomarker assessment indicated higher expression of T-cell-inflamed gene signature at baseline among responding patients. Response to treatment was durable (>24 months) in some patients across all enrolled indications, and safety findings were in accordance with previous and current studies exploring LAG-3/PD-1 blockade."

Combination therapy • IO biomarker • Journal • Metastases • P2 data • Breast Cancer • Dermatology • Fatigue • Genito-urinary Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Pruritus • Renal Cell Carcinoma • Solid Tumor • Triple Negative Breast Cancer

[VIRTUAL] A Phase II, multicenter study of the safety and efficacy of LAG525 in combination with spartalizumab in patients with advanced malignancies (SITC 2020) - P1/2 | "The combination was well tolerated, and no new safety signals were observed. Biomarker analysis is ongoing."

Clinical • Combination therapy • IO Biomarker • P2 data • Breast Cancer • Cutaneous Melanoma • Genito-urinary Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Triple Negative Breast Cancer • PD-L2

Two checkpoint inhibitor combinations in patients with cutaneous melanoma: A systematic review of clinical trials. (ASCO 2022) - "Nivolumab (nivo) + ipilimumab (ipi), relatlimab (rela) + nivo, pembrolizumab (pemb) + ipi, lag525 + spartalizumab (spa), fianlimab (fian) + cemiplimab (cem) and single drug/placebo were used to treat 560, 365, 223, 42, 48, and 1,148 patients, respectively. Two ICI combinations of nivo, ipi, and rela were more effective than monotherapy in patients with untreated advanced melanoma. In early phase trials, combinations of ipi, nivo, pemb, lag525, spa, fian, and cem were effective in advanced melanoma. Nivo, ipi, and rela were effective in patients with resectable melanoma."

Checkpoint inhibition • Clinical • Review • Cutaneous Melanoma • Immune Modulation • Inflammation • Melanoma • Oncology • Solid Tumor • CTLA4 • LAG3 • PD-L1

Phase I/II study of LAG525 spartalizumab (PDR001) in patients (pts) with advanced malignancies. (ASCO 2018) - P1/2; "Treatment was well tolerated with preliminary anti-tumor activity and immune profile modulation observed for LAG525 + spartalizumab. Phase II is ongoing in selected indications."

Clinical • IO biomarker • P1/2 data • PD(L)-1 Biomarker • Hormone Receptor Breast Cancer • Mesothelioma • Triple Negative Breast Cancer

Phase I/II study of LAG525 spartalizumab (PDR001) in patients (pts) with advanced malignancies. (ASCO 2018) - P1/2; "Treatment was well tolerated with preliminary anti-tumor activity and immune profile modulation observed for LAG525 + spartalizumab. Phase II is ongoing in selected indications."

Clinical • IO biomarker • P1/2 data • PD(L)-1 Biomarker • Hormone Receptor Breast Cancer • Mesothelioma • Triple Negative Breast Cancer

A randomized, open-label, open-platform, Phase II study evaluating the efficacy and safety of novel spartalizumab (PDR001) combinations in previously treated unresectable or metastatic melanoma (PLATforM) (AACR 2019) - P2; "Part 1, “selection”, will begin with 3 combination arms: (1) spartalizumab + LAG525 (LAG-3 antibody), (2) spartalizumab + capmatinib (c-MET inhibitor), and (3) spartalizumab + canakinumab (IL-1β antagonist). Previously presented at ESMO 2018, FPN 1304TiP, Weber et al. Reused with permission."

Clinical • IO Biomarker • P2 data • PD(L)-1 Biomarker

Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC). (clinicaltrials.gov) - P1 | N=64 | Terminated | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Terminated; This was a sponsor decision and was not a consequence of any safety concern

IO biomarker • Trial termination • Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • ER • HER-2 • LAG3 • PD-L1 • PGR

PLATforM: Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov) - P2 | N=196 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Metastases • Trial completion • Melanoma • Oncology • Solid Tumor • CD8 • LAG3

Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC). (clinicaltrials.gov) - P1 | N=64 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Oct 2022 ➔ Feb 2023 | Trial primary completion date: Oct 2022 ➔ Feb 2023

IO biomarker • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • ER • HER-2 • LAG3 • PD-L1 • PGR

[VIRTUAL] PLATForM: Descriptive analysis from a randomised, phase II study of novel spartalizumab combinations in previously treated unresectable/metastatic melanoma (ESMO 2021) - P2 | "The selection phase comprised 4 Arms combining spartalizumab with ieramilimab (anti-LAG3 mAb; Arm 1), capmatinib (Arm 2), canakinumab (Arm 3) or ribociclib (Arm 4). Although all tested combinations have been declared futile, Arm 1 data suggest pts with LAG-3+ melanoma may be more likely to respond to spartalizumab + ieramilimab treatment. Consequently, Arm 1A (spartalizumab + ieramilimab) was opened and is currently recruiting pts with previously treated unresectable/metastatic LAG-3+ melanoma."

Clinical • IO biomarker • P2 data • Melanoma • Oncology • Solid Tumor

A randomized, open-label, phase II open platform study evaluating the efficacy and safety of novel spartalizumab (PDR001) combinations in previously treated unresectable or metastatic melanoma (PLATForM) (ESMO 2018) - P2; "The first “selection” part of the study will begin with 3 combination arms: (1) spartalizumab + LAG525 (LAG-3 antibody), (2) spartalizumab + capmatinib (c-MET inhibitor), and (3) spartalizumab + canakinumab (IL-1β antagonist). In the second “expansion” part, efficacy and safety of treatment combination(s) selected during part one will be further investigated. Sample size for part two will be adaptive and based on predictive power calculations considering the results from the selection part."

Clinical • IO biomarker • P2 data • PD(L)-1 Biomarker • Melanoma

PLATforM: Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov) - P2 | N=196 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: May 2023 ➔ Jan 2023

Trial completion date • Melanoma • Oncology • Solid Tumor • CD8 • LAG3

Immutep Quarterly Activities Report (GlobeNewswire) - "TACTI-003 - Phase IIb clinical trial: Recruitment is ongoing for 1st line head and neck squamous cell carcinoma (HNSCC) patients for Immutep’s TACTI-003 trial, with 39 patients out of approximately 154 enrolled to date across the now 24 active trial sites....Recruitment and trial updates are expected to be reported throughout the remainder of 2022 and into 2023....INSIGHT-003 investigator-initiated trial, with 13 out of a total of 20 patients already enrolled....Interim results from the study are expected to be reported in Q4 2022....The patent protects ieramilimab in the member states of the Eurasian Patent Convention, namely Armenia, Azerbaijan, Belarus, Kirgizstan, Kazakhstan, Moldova, Russia, Tajikistan and Turkmenistan. The expiry date of the new patent is 13 March 2035."

Clinical protocol • P1 data • Patent • Trial status • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck

Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC). (clinicaltrials.gov) - P1 | N=64 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jun 2022 ➔ Oct 2022 | Trial primary completion date: Jun 2022 ➔ Oct 2022

IO biomarker • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • ER • HER-2 • LAG3 • PD-L1 • PGR

"#Immutep Announces Second Japanese #Patent Grant For #LAG3 #Antagonist #Antibody #LAG525 $IMMP https://t.co/wp2dbQm6Xg" (@1stOncology)

LAG3

Immutep Announces Second Japanese Patent Grant for LAG-3 Antagonist Antibody LAG525 (GlobeNewswire) - "Immutep Limited...is pleased to announce the grant of patent no. 7030750 entitled 'Antibody molecules to LAG-3 and uses thereof' by the Japanese Patent Office....The claims of the patent are directed to pharmaceutical compositions for use in the treatment of cancer, where the composition comprises LAG525 in a specific dose and for use in a defined treatment regimen. The compositions may also be administered in combination with a second agent such as an anti-PD-1 antibody, an anti-PD-L1 antibody or a chemotherapeutic agent. The patent is co-owned by Novartis AG and Immutep S.A.S., and will expire on 13 March 2035."

Patent • Oncology

PLATforM: Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov) - P2 | N=196 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2023 ➔ Jun 2023 | Trial primary completion date: Aug 2022 ➔ Jan 2023

Enrollment closed • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • CD8 • LAG3

Phase I/II study of the LAG-3 inhibitor ieramilimab (LAG525) ± anti-PD-1 spartalizumab (PDR001) in patients with advanced malignancies. (PubMed, J Immunother Cancer) - P1/2 | "Ieramilimab was well tolerated as monotherapy and in combination with spartalizumab. The toxicity profile of ieramilimab in combination with spartalizumab was comparable to that of spartalizumab alone. Modest antitumor activity was seen with combination treatment."

IO biomarker • Journal • P1/2 data • Dermatology • Fatigue • Gastrointestinal Disorder • Oncology • Solid Tumor • CD8 • LAG3

Study of Safety and Efficacy of Novel Immunotherapy Combinations in Patients With Triple Negative Breast Cancer (TNBC). (clinicaltrials.gov) - P1 | N=64 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=220 ➔ 64 | Trial completion date: Jan 2022 ➔ Jun 2022 | Trial primary completion date: Jan 2022 ➔ Jun 2022

Enrollment change • Enrollment closed • IO biomarker • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • ER • HER-2 • LAG3 • PD-L1 • PGR

PLATforM: Study of Efficacy and Safety of Novel Spartalizumab Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov) - P2; N=195; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Jun 2022 ➔ Jan 2023; Trial primary completion date: Dec 2021 ➔ Aug 2022

Clinical • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • CD8 • LAG3

A Study of Efficacy and Safety of LAG525 in Combination With Spartalizumab, or With Spartalizumab and Carboplatin, or With Carboplatin, in Patients With Advanced Triple-negative Breast Cancer (clinicaltrials.gov) - P2; N=88; Completed; Sponsor: Novartis Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion • Breast Cancer • HER2 Negative Breast Cancer • Immune Modulation • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

[VIRTUAL] A phase II study of LAG525 in combination with spartalizumab (PDR001), PDR001 and carboplatin (Carbo), or Carbo, as first- or second-line therapy in patients (Pts) with advanced (Adv) triple-negative breast cancer (tnbc) (ESMO 2021) - P2 | "As no arms met the PPE criteria, no further investigation is planned. Anaemia was the most common grade ≥3 AE. Exploratory biomarker analyses are ongoing."

Clinical • Combination therapy • IO biomarker • P2 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1