NKTR-262

P1/2, N=64, Terminated, Nektar Therapeutics | Trial completion date: Oct 2022 --> May 2022 | Active, not recruiting --> Terminated; Based on the overall results from the Phase 1 part of the study the sponsor decided to end the study. The decision was not due to safety reasons.

BEMPEG+NKTR-262 therapy elicited more robust expansion of activated CD8 T cells compared with BEMPEG+RT, suggesting that intratumoral TLR stimulation provides superior antigen presentation and costimulatory activity compared with RT. A clinical trial of BEMPEG+NKTR-262 for patients with metastatic solid tumors is in progress (NCT03435640).

P1/2, N=64, Active, not recruiting, Nektar Therapeutics | Trial completion date: Dec 2021 --> Oct 2022 | Trial primary completion date: Sep 2021 --> Jul 2022

Enhancement of the activated CD8+ T cell response in mice treated with NKTR-262 in combination with BEMPEG suggests that intratumoral TLR stimulation provides superior antigen presentation and costimulatory activity compared to RT. A clinical trial of BEMPEG/NKTR-262 for patients with metastatic solid tumors is in progress (NCT03435640).

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.

P1/2, N=64, Active, not recruiting, Nektar Therapeutics | Trial completion date: Dec 2022 --> Dec 2021

P1/2, N=64, Active, not recruiting, Nektar Therapeutics | N=393 --> 64

P1/2, N=393, Active, not recruiting, Nektar Therapeutics | Recruiting --> Active, not recruiting

The improved tumor regression and survival was dependent on the NKTR-262 driven expansion of NK cells. A clinical trial of BEMPEG/NKTR-262 for patients with metastatic solid tumors is in progress (NCT03435640).

The improved tumor regression and survival was dependent on the NKTR-262 driven expansion of NK cells. A clinical trial of BEMPEG/NKTR-262 for patients with metastatic solid tumors is in progress (NCT03435640).

We hypothesized that combination treatment with NKTR-262 and NKTR-214 could provide powerful and synergistic anti-tumor effects as NKTR-262 could potentiate the antigen-presenting cells and convert M2 macrophages to M1 macrophages, and NKTR-214 could stimulate expansion of “educated” CD8+ T cells, which then traffic to distant tumor sites resulting in tumor shrinkage.In preclinical studies, a single intratumoral administration of NKTR-262 combined with systemic administration of NKTR-214 produced a complete cure of treated and untreated tumors in multiple syngeneic models. Currently, NKTR-262 is being evaluated in a Phase 1b/2 clinical trial in patients with locally advanced or metastatic solid tumors.