Fibromun (onfekafusp alfa)

P2, N=98, Recruiting, Philogen S.p.A. | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=0, Withdrawn, Philogen S.p.A. | N=24 --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 Withdrawn

P3, N=102, Recruiting, Philogen S.p.A. | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

P1, N=2, Active, not recruiting, Philogen S.p.A. | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1/2, N=142, Recruiting, Philogen S.p.A. | Trial primary completion date: Nov 2023 --> Mar 2025

P2, N=90, Not yet recruiting, Philogen S.p.A.

P1/2, N=142, Recruiting, Philogen S.p.A.

Subsequent re-challenge with L19TNF and lomustine again led to a partial response. These encouraging results justify further investigations within the phase II part of the clinical trial that is recruiting patients in four countries.

P1, N=2, Active, not recruiting, Philogen S.p.A. | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

P1/2, N=20, Completed, Philogen S.p.A. | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Jun 2023 | Trial primary completion date: Dec 2022 --> Jun 2023

On the basis of these encouraging results, we translated this treatment combination to patients with glioblastoma. The clinical translation is ongoing but already shows objective responses in three of five patients in the first recurrent glioblastoma patient cohort treated with L19TNF in combination with CCNU (NCT04573192).

P1, N=29, Completed, Philogen S.p.A. | Active, not recruiting --> Completed

P1, N=24, Not yet recruiting, Philogen S.p.A.

L19TNF can be safely applied in combination with dacarbazine and induces tumor responses in patients with previously pretreated advanced or metastatic soft tissue sarcomas.

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 interleukin-12 electroporation (pIL-12 EP), IT ipilimumab, INT230-6 (cisplatin and vinblastine with an amphiphilic penetration enhancer), TTI-621 (SIRPαFc), CD-40 agonistic antibodies (ABBV-927 and APX005M), antimicrobial peptide LL37 and other miscellaneous agents.

Furthermore, intravenous administration of L19-mIL12 or L19-mTNF cured a proportion of tumor-bearing mice, whereas L19-IL2 did not. Systemic administration of the fully human L19-TNF fusion protein to patients with glioblastoma (NCT03779230) was safe, decreased regional blood perfusion within the tumor, and was associated with increasing tumor necrosis and an increase in tumor-infiltrating CD4 and CD8 T cells. The extensive preclinical characterization and subsequent clinical translation provide a robust basis for future studies with immunocytokines to treat malignant brain tumors.