Delving into the Latest Updates on RG-7461 with Synapse

Overview

Basic Info

Drug Type

Antibody fusion proteins

Synonyms

Anti-fap/interleukin-2 fusion protein ro6874281, Simlukafusp alfa

+ [5]

Target

FAP x IL-2Rβγ

Mechanism

FAP modulators(Fibroblast activation protein alpha modulators), IL-2Rβγ agonists(Interleukin-2 Rβγ agonists), Immunomodulators

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication

Metastatic Pancreatic Ductal AdenocarcinomaBreast CancerHead and Neck Neoplasms

Inactive Indication

Esophageal CarcinomaMetastatic melanomaMetastatic Solid Tumor+ [2]

Originator Organization

F. Hoffmann-La Roche Ltd.

Active Organization

Hoffmann-La Roche, Inc.

Inactive Organization-

Drug Highest PhasePhase 1/2

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 154438L

Source: *****

Sequence Code 169803H

Source: *****

Sequence Code 154432H

Source: *****

An Open-Label, Multicenter, Phase Ib Study to Evaluate Safety and Therapeutic Activity of RO6874281, an Immunocytokine, Consisting of Interleukin-2 Variant (IL-2v) Targeting Fibroblast Activation Protein-Α (FAP), in Combination with Pembrolizumab (Anti-PD-1), in Participants with Advanced or Metastatic Melanoma

This is an open-label, multicenter, Phase Ib study to evaluate the safety and therapeutic activity of RO6874281 in combination with pembrolizumab. The study will consist of 3 parts: a safety run-in (Part I: Cohorts 1.1. and 1.2) and two expansion parts (Parts II and III). Part II will start once all participants in Cohort 1.1 have completed the observation period. Part III will start once all participants in Cohorts 1.1 and 1.2 have completed the observation period.

Start Date24 Jun 2019

Sponsor / Collaborator

Hoffmann-La Roche, Inc.

100 Clinical Results associated with RG-7461

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100 Translational Medicine associated with RG-7461

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100 Patents (Medical) associated with RG-7461

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8

Literatures (Medical) associated with RG-7461

01 Nov 2024·eBioMedicine

Phase 2 study of the antitumour activity and safety of simlukafusp alfa (FAP-IL2v) combined with atezolizumab in patients with recurrent and/or metastatic cervical squamous cell carcinoma

Article

Author: Richard, Muriel ; Habigt, Christin ; Guerra Alia, Eva Maria ; Sleiman, Nassim ; Lindsay, Colin R. ; Taus, Álvaro ; Deva, Sanjeev ; Oaknin, Ana ; Dejardin, David ; Gumus, Mahmut ; Lindsay, Colin R ; Teichgräber, Volker ; Marbach, Daniel ; Ardeshir, Caroline ; Verlingue, Loic ; Tosi, Diego ; Prenen, Hans ; Arslan, Cagatay ; Lugowska, Iwona ; Boetsch, Christophe ; Rottey, Sylvie ; Kraxner, Anton ; Cicin, Irfan ; Moiseyenko, Vladimir ; Smolin, Alexey ; Charo, Jehad ; Roselló-Keränen, Susana ; Evers, Stefan ; Perets, Ruth ; Dziadziuszko, Rafal ; Keshelava, Nino ; Goksu, Sema Sezgin ; Italiano, Antoine

BACKGROUNDSimlukafusp alfa (FAP-IL2v) is an immune cytokine engineered to selectively promote immune responses in the tumour microenvironment. We evaluated the antitumour activity and safety of FAP-IL2v plus atezolizumab in recurrent and/or metastatic cervical squamous cell carcinoma (SCC) in a phase 2 basket study (NCT03386721).METHODSPatients with confirmed metastatic, persistent or recurrent cervical SCC who had progressed on ≥1 anti-cancer therapy and had measurable disease were enrolled. FAP-IL2v 10 mg was administered once every 3 weeks (Q3W) or once weekly (QW) for 4 weeks then once every 2 weeks (Q2W) with the corresponding Q3W or Q2W atezolizumab regimens. The primary endpoint was objective response rate by investigator assessment.FINDINGSForty-eight patients were enrolled (Q3W: n = 47; QW/Q2W: n = 1). Among 45 response evaluable patients, objective responses occurred in 12 patients (27%; CI 16.0-41.0), including 3 complete and 9 partial responses. Responses occurred in 6/19 PD-L1 positive patients (32%; 95% CI 15.4-54.0) and 5/24 PD-L1 negative patients (21%; 95% CI 9.2-35.6). Median duration of response was 13.3 months (95% CI 7.6-NE). Median progression-free survival was 3.7 months (95% CI 3.3-9.0). Adverse events (AEs) were consistent with the known safety profile of each drug. AEs leading to withdrawal of either agent occurred in 6 patients (13%). Pronounced expansion and activation of natural killer and CD8 T cells in peripheral blood and increased tumour infiltration and inflammation were observed.INTERPRETATIONFAP-IL2v plus atezolizumab is clinically active and has manageable safety in patients with recurrent and/or metastatic cervical SCC.FUNDINGF. Hoffmann-La Roche Ltd.

18 Oct 2024·Clinical cancer research : an official journal of the American Association for Cancer Research

Phase 1b Study of the Immunocytokine Simlukafusp alfa (FAP-IL2v), in Combination with Cetuximab in Patients with Head and Neck Squamous Cell Carcinoma.

Article

Author: Charo, Jehad ; Bonomi, Marcelo R ; Steeghs, Neeltje ; Italiano, Antoine ; Fayette, Jérôme ; Gomez-Roca, Carlos A ; Prenen, Hans ; Spicer, James ; Kraxner, Anton ; Evers, Stefan ; Bauman, Julie E ; Schneider, Meike ; Schmid, Daniela ; Habigt, Christin ; Teichgräber, Volker ; Hansen, Aaron R ; Dejardin, David ; Niu, Jiaxin ; Sleiman, Nassim ; Verlingue, Loic ; Robbrecht, Debbie G J ; Boetsch, Christophe ; Ardeshir, Caroline ; Keshelava, Nino

PURPOSEThis phase 1b trial evaluated FAP-IL2v, a novel immune-cytokine engineered to minimize CD25-mediated toxicities, in combination with cetuximab, in patients with recurrent, unresectable, or metastatic head and neck squamous cell carcinoma (HNSCC).PATIENTS AND METHODSPatients received FAP-IL2v either on a continuous weekly (QW) schedule, or QW for 4 weeks and then every 2 weeks (Q2W). Cetuximab was dosed at QW or Q2W schedules. The primary objectives were to evaluate the safety and tolerability, maximum tolerated dose (MTD), pharmacokinetics, and clinical activity for the combination of FAP-IL2v with cetuximab. Exploratory objectives included pharmacodynamic analyses.RESULTSA total of 58 patients were enrolled, 19 patients into the dose-escalation, and 39 patients into the expansion part. The MTD of FAP-IL2v was defined as 10 mg (QW/Q2W) in combination with cetuximab (500 mg/m2, Q2W), which was further tested in the expansion part. The most common FAP-IL2v-related adverse events with a grade 3 or 4 severity were hypophosphatemia (19%), lymphopenia (16%), and infusion-related reaction (14%). The pharmacokinetics of FAP-IL2v in combination with cetuximab was similar to that after administration as monotherapy. Consistent with the proposed mode-of-action, FAP-IL2v preferentially expanded intratumoral NK and CD8 T cells. Four patients achieved a partial response, the objective response rate was 7% (95% CI: 3.2, 14.7).CONCLUSIONSThe safety profile of FAP-IL2v in combination with cetuximab was acceptable and pharmacodynamic markers support the proposed mode-of-action of this combination, but the overall low antitumor activity does not warrant further clinical exploration in HNSCC. [Part C of Study BP29842 (NCT02627274).].

01 Sep 2024·Cancer Research Communications

Phase I Study of Simlukafusp Alfa (FAP-IL2v) with or without Atezolizumab in Japanese Patients with Advanced Solid Tumors

Article

Author: Seki, Ryoko ; Yoshida, Tatsuya ; Imaizumi, Tatsuki ; Katsuya, Yuki ; Sudo, Kazuki ; Koyama, Takafumi ; Sato, Jun ; Enomoto, Masashi ; Yonemori, Kan ; Yamamoto, Noboru ; Shimizu, Toshio ; Kondo, Shunsuke

AbstractPurpose:The aim of the study was to evaluate the safety/tolerability and pharmacokinetics of simlukafusp alfa (FAP-IL2v), an immunocytokine containing an anti-fibroblast activation protein-α (FAP) antibody and an IL2 variant, administered alone or with the PDL1 inhibitor atezolizumab, in Japanese patients with advanced solid tumors.Patients and Methods:In this phase 1, open-label, dose-escalation study, patients received i.v. FAP-IL2v at 10 or 15/20 mg alone or 10 mg when combined with i.v. atezolizumab. The primary objectives were identification of dose-limiting toxicities (DLT), recommended dose, and maximum tolerated dose, and evaluation of the safety/tolerability and pharmacokinetics of FAP-IL2v alone and combined with atezolizumab.Results:All 11 patients experienced adverse events (AE) during FAP-IL2v treatment. Although most AEs were of mild severity, four treatment-related AEs led to study treatment discontinuation in two patients: one with infusion-related reaction, hypotension, and capillary leak syndrome, and the other with increased aspartate aminotransferase. No AE-related deaths occurred. One DLT (grade 3 hypotension) occurred in a patient receiving FAP-IL2v 15/20 mg alone. The recommended dose and maximum tolerated dose could not be determined. The pharmacokinetics of FAP-IL2v remained similar with or without atezolizumab. The study was terminated early as FAP-IL2v development was discontinued because of portfolio prioritization (not for efficacy/safety reasons).Conclusions:This study describes the safety/tolerability of FAP-IL2v 10 mg alone and in combination with atezolizumab in Japanese patients with advanced solid tumors; one DLT (hypotension) occurred with FAP-IL2v 15/20 mg. However, dose escalation of FAP-IL2v was not conducted because of early study termination.Significance:This phase I study assessed the safety/tolerability and PK of simlukafusp alfa alone or combined with atezolizumab in Japanese patients with advanced solid tumors. No notable differences in PK were noted with the combination versus simlukafusp alfa alone; however, high-dose simlukafusp alfa treatment was associated with recombinant IL2-related toxicity, despite the drug's FAP targeting and IL2Rβγ-biased IL2 variant design.

100 Deals associated with RG-7461

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Esophageal Carcinoma	Phase 2	CH	Hoffmann-La Roche, Inc.	19 Feb 2018
Esophageal Carcinoma	Phase 2	IL	Hoffmann-La Roche, Inc.	19 Feb 2018
Esophageal Carcinoma	Phase 2	TW	Hoffmann-La Roche, Inc.	19 Feb 2018
Esophageal Carcinoma	Phase 2	DE	Hoffmann-La Roche, Inc.	19 Feb 2018
Esophageal Carcinoma	Phase 2	GB	Hoffmann-La Roche, Inc.	19 Feb 2018
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 2	ES	Hoffmann-La Roche, Inc.	05 Jul 2017
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 2	US	Hoffmann-La Roche, Inc.	05 Jul 2017
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 2	KR	Hoffmann-La Roche, Inc.	05 Jul 2017
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 2	DE	Hoffmann-La Roche, Inc.	05 Jul 2017
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 2	JP	Hoffmann-La Roche, Inc.	05 Jul 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03386721 (Pubmed) Manual	Phase 2	Esophageal Carcinoma First line	34	FAP-IL2v + atezolizumab	(sdtehizcee) = mfwxqyhkzh vqmwhsdfnk (mkfbuunwev, 10.4 - 36.8) View more	Positive	06 May 2024
NCT02627274 (BP29842, ESMO2021) Manual	Phase 1	Squamous Cell Carcinoma of Head and Neck Second line	46	Simlukafusp alfa+cetuximab	(thsnhgbqbh) = ezakrqzxuh noqhkyllzh (otbpcxiiyy ) View more	Negative	16 Sep 2021
NCT03063762 (ASCO2021) Manual	Phase 1	Unresectable Renal Cell Carcinoma	69	atezolizumab+simlukafusp α (Arm A)	(pfcfvgnoga) = oqlcdgjbhp gpcghibfjz (isxbqmycxj, 12.95 - 40.12) View more	Positive	20 May 2021
NCT03063762 (ASCO2021) Manual	Phase 1	Unresectable Renal Cell Carcinoma	69	atezolizumab+bevacizumab+simlukafusp α (Arm B)	(pfcfvgnoga) = xhxstejhhp gpcghibfjz (isxbqmycxj, 27.67 - 66.68)	Positive	20 May 2021
NCT03193190 (MORPHEUS-PDAC, ESMO_GI2020)	Phase 1/2	Pancreatic Ductal Adenocarcinoma Second line FAP \| IL-2v	-	Atezolizumab plus RO6874281 Q3W	(igglwzjbdz) = qoxbojwthp keygbavbcz (wsdtquxrbi, 1.4 - 2.7)	Negative	08 Jul 2020
NCT03193190 (MORPHEUS-PDAC, ESMO_GI2020)	Phase 1/2	Pancreatic Ductal Adenocarcinoma Second line FAP \| IL-2v	-	Atezolizumab plus RO6874281 Q2W	(ziscaxrfmz) = bcdfeddjfw qwfumhqobk (zazxfljptx ) View more	Negative	08 Jul 2020
NCT02627274 (ESMO2018) Manual	Phase 1	Metastatic Solid Tumor	16	RO6874281	(hrdaqkmcum) = mild or moderate rebugyouwf (qqhyscxclb ) View more	Positive	20 Oct 2018