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27 oktober 2026: bron: persbericht National Institutes of Health (NIH), Mass General Brigham and Memorial Sloan Kettering

Wanneer patiënten met vergevorderde therapieresistente vormen van kanker met solide tumoren als laatste mogelijkheid een doelgerichte vorm van immuuntherapie krijgen met Invikafusp alfa afgekort Invika, een zogenaamd bispecifieke duaal T-cel agonistische antilichaam, dan blijkt de ziekteprogressie bij de meeste patiënten te stoppen. En bij sommige patiënten verminderde de tumor zelfs in omvang. Bij patiënten met solide tumoren die niet reageerden op standaard immuuntherapie, werd de ziekteprogressie in de meeste gevallen dus gestopt, terwijl bij sommige patiënten de tumoren zelfs in omvang afnamen. Aldus tussenresultaten uit de Start-001 studie. 

Van de 27 deelnemers die in beide fasen de optimale dosering ontvingen, bleef de ziekte bij 16 personen (59,3%) stabiel dus geen ziekte progressie. Bij vier deelnemers (14,8%) krompen de kwaadaardige tumoren met meer dan 30%. Twee van hen leden aan uitgezaaide darmkanker – met tumoren die bekendstaan ​​als zeer resistent tegen behandelingen – en zij ontvingen invika als zevendelijnsbehandeling. Een andere patiënt die positief reageerde, had stadium 4 niet-kleincellige longkanker; ook hier ging het om tumoren die ongevoelig waren gebleken voor diverse eerdere therapieën, waaronder ICB.

De wetenschappers hebben het eiwit  Invikafusp alfa afgekort Invika zo ontworpen dat het zich richt op een specifieke subgroep van T-cellen, namelijk twee groepen lymfocyten die in tumoren doordringen. Doordat invika enkel deze twee specifieke T-cellen activeert – en niet alle T-cellen tegelijk – wordt de afweer tegen de tumor versterkt, terwijl de ernstige bijwerkingen die bij minder selectieve methoden kunnen optreden, worden vermeden.
Preklinische studies laten zien dat het middel zijn doelwit bereikt en de afweer tegen tumoren stimuleert in diermodellen.

Deze nieuwe studie beschrijft de volgende stap voor invika en presenteert de resultaten van fase 1- en de eerste fase 2-experimenten bij mensen. De onderzoekers die de studie leidden, selecteerden patiënten met uiteenlopende vormen van kanker, van wie het merendeel niet goed had gereageerd op immuuntherapie met anti-PD medicijnen.
In fase 1 kregen de deelnemers elke twee weken wisselende doseringen van het middel 'invika' toegediend, om zo de veiligheid te evalueren en de optimale dosering te bepalen.
Hoewel sommige deelnemers griepachtige bijwerkingen ervoeren, waren deze voorzien en doorgaans goed te beheersen met aanvullende medicatie en ondersteunende zorg. Nadat de laagste dosering was vastgesteld waarbij het gewenste effect maximaal was, gingen de onderzoekers over naar fase 2, waarin de deelnemers met deze optimale dosering werden behandeld.

"Patiënten met vergevorderde tumoren – zeker tumoren die niet goed reageren op immuuntherapie – staan ​​vaak met de rug tegen de muur. In zo’n stadium zijn er nog maar weinig behandelopties over. Deze resultaten wijzen echter op een nauwkeurigere manier om de afweer tegen tumoren te stimuleren, wat een nieuwe oplossing zou kunnen bieden," aldus co-corresponderend auteur James Gulley, M.D., Ph.D., klinisch directeur bij het Center for Cancer Research (CCR), onderdeel van het National Cancer Institute (NCI) van de NIH.

De sponsor van de behandeling, Marengo Therapeutics, heeft eerder bekendgemaakt dat de Amerikaanse Food and Drug Administration (FDA) de status 'Fast Track' heeft toegekend aan invika. Hiermee wordt de beoordeling van het middel als behandeling voor antigeenrijke, uitgezaaide darmkanker versneld.

Meer recent heeft de FDA dezelfde status toegekend aan invika voor vergelijkbare solide tumoren – ongeacht het weefseltype – bij patiënten die al een eerdere behandeling hebben ondergaan, waaronder therapie met anti-PD medicijnen -  checkpointremmers.

Voor de lopende klinische studie worden nog deelnemers gezocht. Patiënten die interesse hebben in deelname aan dit onderzoek, kunnen contact opnemen met het gratis telefoonnummer van het NCI: 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615), of een e-mail sturen naar NCIMO_referrals@mail.nih.gov.

De tussenresultaten zijn ook gepubliceerd op 23 oktober 2026:

Abstract

Invikafusp alfa (invika), a first-in-class, bispecific, dual T cell agonistic antibody selectively targeting Vβ6/Vβ10 T cell subsets, is being evaluated in START-001, a multicenter phase 1/2 monotherapy trial in participants with mostly immune checkpoint blockade (ICB)-resistant, antigen-rich solid tumors. Primary outcomes were safety/tolerability and recommended phase 2 dose (RP2D) in phase 1 and anti-tumor activity in phase 2. As of 12 March 2025, phase 1 completed dose escalation (n = 34) through dose levels of 0.01, 0.02, 0.04, 0.08, 0.12 and 0.16 mg kg-1 without reaching maximum tolerated dose, and initial phase 2 enrolled 18 participants. Two participants experienced reversible dose-limiting toxicities, one at each of the 0.08 mg kg-1 and 0.16 mg kg-1 dose levels. The most common treatment-related adverse event was cytokine release syndrome, mainly grades 1 and 2. No treatment-related deaths or non-laboratory grade 4 adverse events were reported. At the optimal biological doses (OBDs; 0.08 mg kg-1 and 0.12 mg kg-1) in combined phase 1 and phase 2 cohorts, the overall objective response rate was 14.8% (4/27), including confirmed partial responses in immunologically cold tumors, such as microsatellite stable colorectal cancer and programmed death-ligand 1 (PD-L1)-negative non-small cell lung cancer. No objective responses were seen at doses lower than 0.08 mg kg-1. Invika selectively and potently expanded peripheral and intratumoral Vβ6/Vβ10 T cells, of a predominantly memory-like phenotype, dose-dependently, peaking at the OBDs. Pharmacodynamic increases in interferon-γ and soluble CD25 followed a similar pattern. Integrated analyses from safety, pharmacokinetic, pharmacodynamic and preliminary anti-tumor data supported the selection of 0.08 mg kg-1 as the RP2D. In conclusion, phase 1 of START-001 met its primary outcomes by demonstrating the acceptable safety profile of invika consistent with its mechanism of action and selecting an RP2D. Initial phase 2 results further corroborated the safety of invika and expanded its preliminary evidence of clinically meaningful anti-tumor activity in ICB-resistant solid tumors, supporting further evaluation in the ongoing phase 2. ClinicalTrials.gov identifier: NCT05592626 .

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Conflict of interest statement

Competing interests: R.J.S. has received research funding (to institution) from BioNTech SE, Bristol Myers Squibb, Genentech/Roche, Georgiamune, Immunocore, Marengo Therapeutics, Merck, Moderna, Novartis, Pfizer, Relay, Springworks and Synthekine and has been a consultant/advisory board member for Marengo Therapeutics, Merck, Novartis, Pfizer, PharmaMar and Replimune. N.P.T., R.N.D., J.S. and J.L.G. work for NCI, NIH, which has a Cooperative Research and Development Agreement (CRADA) with Marengo Therapeutics. This CRADA provides resources for co-development of invikafusp alfa. These NIH authors do not have any competing interests to disclose. C.F.F. is an employee of Lilly and receives institutional funding to Memorial Sloan Kettering Cancer Center. M.H., M.P. and M.R.-D. have nothing to disclose. G.P.S. is on the advisory board for EMD Serono, Bristol Myers Squibb, Merck, Seattle Genetics, Astellas, Janssen, Bicycle Therapeutics, Pfizer, Gilead, Lilly, Loxo Oncology, Aktis, Daiichi Sankyo, GlaxoSmithKline and Abbott; serves as a consultant or member of the scientific advisory board/trial steering committee for Merck, Ellipses, Lucence and Coiled Therapeutics; receives research support (to institution) from EMD Serono, Jazz Pharmaceuticals, Bayer, Sumitomo Pharma and Blue Earth Diagnostics; is a speaker for Seagen, Gilead, Natera, Exelixis, Janssen, Astellas, Bayer, Aveo, Pfizer, Merck and AstraZeneca; and has received travel support from Bristol Myers Squibb, Astellas and Merck. G.P.S.ʼs spouse is employed by Myriad, Exact Sciences and Abbott. K.H. (current affiliation: The University of Texas at San Antonio Mays Cancer Center) has received research funding (to institution) from A2bio, AbbVie, Adaptimmune, Amgen, BioNTech SE, Bristol Myers Squibb, Genentech/Roche, GlaxoSmithKline, Iovance Biotherapeutics, Marengo Therapeutics, Mirati Therapeutics, Obsidian Therapeutics, OncoC4, Servier and Synthekine and is a consultant for Amgen, AstraZeneca, BioNTech SE, Bristol Myers Squibb, Iovance Biotherapeutics, Lyell Immunopharma, Mirati Therapeutics, Perthera, Pfizer, Obsidian Therapeutics, Lilly, OncoC4 and Synthekine. A.I. receives research support (to institution) from AstraZeneca, Bayer, Bristol Myers Squibb, F. Hoffmann-La Roche and Merck and consultant fees (personal) from Chugai Pharmaceutical. A.M. has received travel funding from Bristol Myers Squibb, Roche/Genentech, Incyte and MSD; has acted in a consulting or advisory role for Adagene, AstraZeneca, BioLineRx, Centessa Pharmaceuticals, Clover Biopharmaceuticals, Deka Biosciences, Depth Charge Therapeutics, Eisai, Greywolf Therapeutics, Gritstone Bio, Guidepoint Global, HiFiBiO Therapeutics, Hotspot Therapeutics, Innate Pharma, lmCheck Therapeutics, Johnson & Johnson/Janssen, Lytix Biopharma, Medicxi, MSD, Neogene Therapeutics, OSE Immunotherapeutics, PegaOne, Pierre Fabre, Roche, Redx Pharma, Sanofi, Servier, Shattuck Labs, Sotio and Third Rock Ventures; and has stock or ownership in Centessa Pharmaceuticals, Deka Biosciences, HotSpot Therapeutics, Marengo Therapeutics and Shattuck Labs. F.-X.D. holds a consulting or advisory role for Merck KGaA. E.G.C. has received funding (to institution) from Novartis, Roche, Thermo Fisher Scientific, AstraZeneca, Taiho, BeiGene Medicines, Janssen and Anaveon; consulting fees from Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Skypta, Sotio, Sanofi, AbbVie, Astex Therapeutics, Alentis Therapeutics, Marengo Therapeutics, Incyte, Lilly, Medpace, Pfizer, Amgen, GenMab, Genentech, Greywolf Therapeutics, Gilead, Daiichi Sankyo, Takeda Pharmaceuticals, Pyramid Biosciences, Epics Therapeutics, Ayuvant Biotech, Apmonia Therapeutics and Cancer Research Horizons; and honoraria for speaking bureaus from Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Skypta, Sotio, Sanofi, Anaveon, AbbVie, Astex Therapeutics, Alentis Therapeutics, Marengo Therapeutics, Incyte, Lilly, Medpace, Pfizer, Amgen, GenMab, Genentech, Greywolf Therapeutics, Gilead, Daiichi Sankyo, Takeda Pharmaceuticals, Pyramid Biosciences, Epics Therapeutics, Ayuvant Biotech, Apmonia Therapeutics and Cancer Research Horizons. She is an employee of NEXT Oncology and holds stock in 1TRIALSP. A.H.-C. reports advisory council or committee membership from Boehringer Ingelheim, Karger Publishers and Slingshot Insights; honoraria from CDDF and Fundación SEOM; and grants or funds (to institution) from Bayer, Bicara Therapeutics, Boehringer Ingelheim, CDR-life, Gilead, GlaxoSmithKline, NEC Bio, Novartis and Vividion Therapeutics (all institution). A.P. receives consulting fees (personal) from Pfizer, Roche (Data and Safety Monitoring Committee), Biofidelity, Bristol Myers Squibb, Checkmate Pharmaceuticals, CVS Caremark Corporation, Lilly, Zola and Inivata and fees paid to institution from Novartis, PMV Pharmaceuticals, PureTech Health, Daiichi Sankyo, Genentech and Mirati Therapeutics. G.I. reports institutional research funding from AADi, Flare Therapeutics, Janssen, Loxo Oncology/Lilly and Pfizer and personal/consulting or advisory fees from AstraZeneca, Bicycle Therapeutics, Daiichi Sankyo, EMD Serono, Flare Therapeutics, Janssen Research and Development, Loxo Oncology/Lilly, Mirati Therapeutics and Pfizer, outside the submitted work. A.Z. is on the speaker program for Inocyte, BeOne Medicines, Exelixis, AstraZeneca and Geron. E.J.W. is an advisor for Arpelos Bio, Arsenal Biosciences, Coherus, Danger Bio, IpiNovyx, New Limit, Marengo Therapeutics, Pluto Immunotherapeutics, Related Sciences, Santa AnaBio and Synthekine; is a founder of Arpelos Bio, Arsenal Biosciences and Danger Bio; and holds stock in Coherus. S.M., S.C., K.S., L.B,. M.K., Z. Shun, K.C., Z. Su and K.L. are employees of Marengo Therapeutics. L.L.S. is a consultant/advisory board member for Merck, Roche, Voronoi, GlaxoSmithKline, Bayer, Pfizer, Arvinas, Daiichi Sankyo, Amgen, Pangea, Tubulis, LTZ Therapeutics, Marengo Therapeutics, AstraZeneca, Incyte, Gilead, Bristol Myers Squibb, Systinn, Systimmune, EMD Serono and MBrace. Her institution receives grant/research (clinical trials) support from Bristol Myers Squibb, Roche/Genentech, GlaxoSmithKline, Merck, Novartis, Pfizer, AstraZeneca, Boehringer Ingelheim, Bayer, Amgen, AbbVie, EMD Serono, Daiichi Sankyo, Gilead, Marengo Therapeutics, Incyte, Legochem, Lilly and Daiichi Sankyo. She has stock ownership in Marengo Therapeutics and MBrace. Her spouse is a co-founder of Treadwell Therapeutics. The other authors declare no competing interests.

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immuuntherapie, T-cellen, immuunresistent, therapieresistent, solide tumoren, fase 1/2 studie, Invika, Invikafusp alfa, ziekteprogressie


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