LHC165 / Novartis - LARVOL DELTA

A phase I trial of LHC165 single agent and in combination with spartalizumab in patients with advanced solid malignancies. (PubMed, ESMO Open) - "LHC165 demonstrated acceptable safety and tolerability both as SA and in combination with spartalizumab, and evidence of limited antitumor activity was seen in adult patients with relapsed/refractory or metastatic solid tumors."

Combination therapy • Journal • Metastases • P1 data • Dermatology • Oncology • Pancreatic Cancer • Pancreatitis • Pruritus • Solid Tumor

Pipeline Moves: Novartis Phase I/Ib cancer trial terminates, further study chances drop (Clinical Trials Arena) - "Novartis’s LHC-165 saw its Phase Transition Success Rate (PTSR) slump in three cancer indications after a Phase I/Ib trial was terminated. The PTSR dropped by 35 points to 25% in metastatic melanoma and head and neck cancer squamous cell carcinoma, and 21 points to 15% in solid tumours...The Phase I/Ib trial (NCT03301896) was terminated owing to business reasons, according to its ClinicalTrials.gov listing. GlobalData evaluated the asset on 2 August after the update the day before. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next."

Trial termination • Oncology • Solid Tumor

Study of the Safety and Efficacy of LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1 | N=45 | Terminated | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Terminated; Business reasons

Combination therapy • Trial termination • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

[VIRTUAL] Phase I study of LHC165 ± spartalizumab (PDR001) in patients (pts) with advanced solid tumors (AACR 2021) - P1 | "LHC165 ± spartalizumab demonstrated safety, tolerability, and evidence of preliminary antitumor activity. Exposure to LHC165 increased with dose, no interaction was observed with spartalizumab. Increased systemic cytokines and T-cell inflammation after LHC165 suggests active TLR7 agonism."

Clinical • IO biomarker • P1 data • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD68 • CD8 • CXCL10 • IFNG • IL6

Current status of intralesional agents in treatment of malignant melanoma. (PubMed, Ann Transl Med) - "This review focuses on the current status of IT agents currently under clinical trials in melanoma. Reviewed therapies include T-VEC, T-VEC with immune checkpoint inhibitors including ipilimumab and pembrolizumab or other agents, RP1, OrienX010, Canerpaturev (C-REV, HF10), CAVATAK (coxsackievirus A21, CVA21) alone or in combination with checkpoint inhibitors, oncolytic polio/rhinovirus recombinant (PVSRIPO), MAGE-A3-expressing MG1 Maraba virus, VSV-IFNbetaTYRP1, suicide gene therapy, ONCOS-102, OBP-301 (Telomelysin), Stimulation of Interferon Genes Pathway (STING agonists) including DMXAA, MIW815 (ADU-S100) and MK-1454, PV-10, toll-like receptors (TLRs) agonists including TLR-9 agonists (SD-101, CMP-001, IMO-2125 or tilsotolimod, AST-008 or cavrotolimod, MGN1703 or lefitolimod), CV8102, NKTR-262 plus NKTR-214, LHC165, G100, intralesional interleukin-2, Daromun (L19IL2 plus L19TNF), Hiltonol (poly-ICLC), electroporation including calcium electroporation and plasmid..."

Journal • Review • Gene Therapies • Immune Modulation • Inflammation • Melanoma • Oncology • Solid Tumor • CD40 • IL12A • MAGEA3 • TYRP1

Study of the Safety and Efficacy of LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1; N=45; Active, not recruiting; Sponsor: Novartis Pharmaceuticals; Recruiting ➔ Active, not recruiting; N=80 ➔ 45

Clinical • Combination therapy • Enrollment change • Enrollment closed • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Study of the Safety and Efficacy of LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1; N=80; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial primary completion date: Jun 2021 ➔ Jan 2022

Clinical • Combination therapy • Trial primary completion date • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Study of the Safety and Efficacy of LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1; N=80; Recruiting; Sponsor: Novartis Pharmaceuticals; N=200 ➔ 80; Trial completion date: Dec 2021 ➔ Mar 2022

Clinical • Combination therapy • Enrollment change • Trial completion date • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Study of the Safety and Efficacy of LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1; N=200; Not yet recruiting; Sponsor: Novartis Pharmaceuticals

Clinical • Combination therapy • New P1 trial

Study of the Safety and Efficacy of LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies (clinicaltrials.gov) - P1; N=200; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Aug 2019 ➔ Dec 2021; Trial primary completion date: Jun 2019 ➔ Apr 2021

Clinical • Combination therapy • Trial completion date • Trial primary completion date

Identification and characterization of LHC165, a TLR7 agonist designed for localized intratumoral therapies (AACR 2019) - "Intratumoral studies in syngeneic preclinical studies show single agent activity and a benefit when dosed in combination with checkpoint blockade. LHC165 as a single agent and in combination with PDR001 is currently enrolling patients with advanced malignancies in CLHC165X2101."

Identification and characterization of LHC165, a TLR7 agonist designed for localized intratumoral therapies (ACS-Sp 2019) - "Intratumoral studies in syngeneic preclinical studies show single agent activity and a benefit when dosed in combination with checkpoint blockade. LHC165 as a single agent and in combination with PDR001 is currently enrolling patients with advanced malignancies in CLHC165X2101."

Development and characterization of LHC165, a TLR7 agonist designed for localized intratumoral injection (ACS-Sp 2019) - "Innovative experiments using pork meat synringeability testing with statistical rigor resulted in an efficient and effective early product development approach. LHC165 as a single agent and in combination with PDR001 is currently enrolling patients with advanced malignancies in CLHC165X2101."