Safety and efficacy of intratumourally administered INT230-6 in adult patients with advanced solid tumours: results from an open-label phase 1/2 dose escalation study
- PMID: 41168074
- DOI: 10.1016/j.ebiom.2025.105980
Safety and efficacy of intratumourally administered INT230-6 in adult patients with advanced solid tumours: results from an open-label phase 1/2 dose escalation study
Abstract
Background: Systemic chemotherapeutics have limited efficacy in many advanced solid tumours. This study evaluated the safety and tolerability of INT230-6, a unique intratumoural (IT) formulation of cisplatin, vinblastine, and 8-((2-hydroxybenzoyl)amino)octanoate (SHAO), an amphiphilic cell-penetration enhancer.
Methods: In this single-arm phase 1/2 trial (NCT03058289), adults with advanced or metastatic disease who progressed on a median of three prior therapies received multiple doses of IT INT230-6 monotherapy once every 28 days or biweekly for five treatments with maintenance dosing every 9 weeks. INT230-6 dose was based on tumour diameter or volume and escalated across five cohorts. A fixed-dose cohort received up to 175 mL.
Findings: No dose-limiting toxicities were reported among 64 enrolled patients; seven (10·9%) discontinued treatment due to adverse events (AEs). Overall, 52/64 (81·3%) patients had treatment-related AEs (TRAEs), including grade ≥3 TRAEs (7/64 [10·9%]) and serious TRAEs (3/64 [4·7%]). INT230-6 achieved a disease control rate (DCR) of 75% (48/64 patients) and median overall survival (mOS) of 11·9 months (95% confidence interval [CI]: 6·3-19·4). In an exploratory analysis, patients dosed at ≥40% of total tumour burden vs <40% had improved DCR (40/48 [83·3%] vs 8/16 [50%]) and mOS (18·7 months [95% CI: 11·5-23·5] vs 3·1 months [95% CI: 1·6-5·9]). Fifteen patients survived ≥21 months; eight were alive at study end. INT230-6 induced a qualitative decrease in proliferating cancer cells in injected tumours and a qualitative increase in activated T-cells infiltrating the tumour microenvironment. Ten patients had abscopal responses.
Interpretation: IT INT230-6 was well tolerated and manifested promising treatment benefits.
Funding: Intensity Therapeutics, Inc.
Keywords: Abscopal effect; Advanced solid cancers; Cell-penetration enhancer; Disease control rate; INT230-6; Intratumoural delivery; Overall survival.
Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of interests JST reports personal fees for participation on data safety monitoring or advisory boards for Coherus BioSciences, Inc and Kura Oncology, Inc. LLS reports funding from 23andMe, Inc, AbbVie Inc, Amgen Inc, AstraZeneca/Medimmune, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Daiichi Sankyo Company, EMD Serono Inc., Gilead Sciences, Inc., GSK, Incyte Corporation, Marengo Therapeutics, Inc., Merck & Co., Inc., Novartis AG, Pfizer Inc/Seagen, Roche/Genentech, and Symphogen A/S to her institution to support the conduct of clinical trials. LLS reports participation on data safety monitoring or advisory boards and consulting fees from Merck & Co., Inc., Pfizer Inc, AstraZeneca, Roche, GSK, VORONOI, Inc., Arvinas, Navire Pharma, Relay Therapeutics, Marengo Therapeutics, Inc., Daiichi Sankyo Company, Amgen Inc, Medicenna Therapeutics, LTZ Therapeutics Inc., Tubulis GmbH, Nerviano Medical Sciences S.r.l, Pangaea Biomed, and Incyte Corporation. LLS’ spouse is in a leadership or fiduciary role for Treadwell Therapeutics and owns stock/stock options in Agios Pharmaceuticals, Inc. MI reports funding to his institution from Pyxis Oncology, Mirati Therapeutics, Inc., BioAtla Inc, PTC Therapeutics, Merck & Co., Inc., and Epizyme; unpaid leadership role at the National Leiomyosarcoma Foundation; and owns stock options in Regeneron Pharmaceuticals Inc. CFM reports royalties or licences and participation on data safety monitoring or advisory boards of Deciphera Pharmaceuticals, LLC and Daiichi Sankyo Company. LHC reports speaker fees from Merck & Co., Inc. and travel grants from Cardinal Health. ARAR reports grants or contracts from 23andMe, Abbisko Therapeutics, AbbVie Inc, Adaptimmune, Amgen Inc, AstraZeneca, Bayer AG, BioNTech SE, Blueprint Medicines Corporation, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Cogent Biosciences, Inc., Daiichi Sankyo Company, Deciphera Pharmaceuticals, LLC, Frontier Biotechnologies Inc., Gilead Sciences, Inc., GSK, Iterion Therapeutics, Karyopharm Therapeutics, Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., MedImmune, Medison Pharma, Merck & Co., Inc., Neoleukin Therapeutics, Inc, Novartis AG, Pfizer Inc, Polaris Group, Roche/Genentech, Rain Oncology, and Symphogen A/S; consulting fees from Boehringer Ingelheim International GmbH, Medison Pharma, Clinical Research Malaysia; payment or honoraria from Medison Pharma; payment for expert testimony from Medison Pharma; and participation on data safety monitoring or advisory boards of Inhibrx Biosciences, and Life CD40. FA owns stock/stock options in Intensity Therapeutics and Sapience Therapeutics, Inc. IBW holds a leadership role (Chief Medical Officer) at Intensity Therapeutics and owns stock/stock options in Intensity Therapeutics. LHB holds a leadership role (Chief Executive Officer) at Intensity Therapeutics and owns stock/stock options in Intensity Therapeutics. ABEK reports grants or contracts from AstraZeneca, Astex Pharmaceuticals, Fulgent Genetics, Auransa Inc.; consulting fees from ABL Bio, Inc., Agenus Inc, AstraZeneca/MedImmune, Bristol-Myers Squibb Company, Eisai Co., Ltd., Exelixis, Inc, Gilead Sciences, Inc., Merck & Co., Inc., Pieris Pharmaceuticals, Inc, QED Therapeutics, Qurient Co., LTD, Roche, Senti Bio, Servier Pharmaceuticals LLC, Tallac Therapeutics, Inc, Terumo Europe NV, Elevar Therapeutics, Roche/Genentech; and support for attending meetings or travel from Affimed GmbH. NSA, AJO, GFW, JSH, DLH, PMC, and SM have no competing interests to declare.
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