An Open-Label, Multicenter, Randomized, Dose-Escalation and Extension, Phase IA/IB Study to Evaluate Safety and Anti-Tumor Activity of RO7284755, A PD-1 Targeted IL-2 Variant (IL-2V) Immunocytokine, Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors

This is an entry-into-human study and will assess the effects of eciskafusp alfa (RO7284755) as a single agent and in combination with atezolizumab in adult participants with solid tumors considered responsive to checkpoint inhibition blockade. The maximum duration in the study for each participant will be up to 28 months.

Start Date04 May 2020

Sponsor / Collaborator

Roche Holding AG

100 Clinical Results associated with Eciskafusp alfa(Roche)

100 Translational Medicine associated with Eciskafusp alfa(Roche)

100 Patents (Medical) associated with Eciskafusp alfa(Roche)

Literatures (Medical) associated with Eciskafusp alfa(Roche)

31 Dec 2023·OncoImmunology

Beyond checkpoint inhibition: PD-1 cis-targeting of an IL-2Rβγ-biased interleukin-2 variant as a novel approach to build on checkpoint inhibition

Article

Author: Hashimoto, Masao ; Umana, Pablo ; Klein, Christian ; Codarri Deak, Laura

The immunocytokine PD1-IL2v was designed to overcome liabilities and improve efficacy of IL-2 therapies. PD1-IL2v preferentially targets PD-1⁺ T-cells and acts on antigen-specific stem-like PD-1⁺ TCF-1⁺ CD8⁺ T-cells expanding and differentiating them towards better effectors resulting in superior efficacy in LCMV chronic infection and tumor models compared to checkpoint inhibition.

IL15/IL15Rα complex induces an anti-tumor immune response following radiation therapy only in the absence of Tregs and fails to induce expansion of progenitor TCF1+ CD8 T cells

Article

Author: Karam, Sana D ; Zhu, Yuwen ; Yee, Elliot ; Knitz, Michael ; Larson, Keira Y. ; Amann, Maria ; Larson, Keira Y ; Gadwa, Jacob ; Karam, Sana ; Saviola, Anthony ; Klein, Christian ; Piper, Miles ; Yee, Elliott ; Hodgson, Chloe

AbstractBackgroundThis work seeks to understand whether IL15-incorporating treatments improve response to radiotherapy and uncover mechanistic rationale for overcoming resistance to IL15 agonism using novel therapeutic combinations.Experimental DesignOrthotopic tumor models of PDAC were used to determine response to treatment. IL15-/- and Rag1-/- mouse models were employed to determine dependence on IL15 and CTLs, respectively. Flow cytometry was used to assess immune cell frequency and activation state. Phospho-proteomic analyses were used to characterize intracellular signaling pathways.ResultsWe show that the combination of radiation therapy (RT) and an IL15/IL15Ra fusion complex (denoted IL15c) fails to confer anti-tumor efficacy; however, a CD8-driven anti-tumor immune response is elicited with the concurrent administration of an aCD25 Treg-depleting antibody. Using IL15-/- and Rag1-/- mice, we demonstrate that response to RT + IL15c + aCD25 is dependent on both IL15 and CTLs. Furthermore, despite an equivalent survival benefit following treatment with RT + IL15c + aCD25 and combination RT + PD1-IL2v, a novel immunocytokine with PD-1 and IL2Rβγ binding domains, CTL immunophenotyping and phospho-proteomic analysis of intracellular metabolites showed significant upregulation of activation and functionality in CD8 T cells treated with RT + PD1-IL2v. Finally, we show the immunostimulatory response to RT + PD1-IL2v is significantly diminished with a concurrent lack of TCF+ CD8 T cell generation in the absence of functional IL15 signaling.ConclusionsOur results are illustrative of a mechanism wherein unimpeded effector T cell activation through IL2Rβ signaling and Treg inhibition are necessary in mediating an anti-tumor immune response.

100 Deals associated with Eciskafusp alfa(Roche)

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Solid Tumor	Phase 1	PL	Roche Holding AG	04 May 2020
Metastatic Solid Tumor	Phase 1	NL	Roche Holding AG	04 May 2020
Metastatic Solid Tumor	Phase 1	CA	Roche Holding AG	04 May 2020
Metastatic Solid Tumor	Phase 1	BE	Roche Holding AG	04 May 2020
Metastatic Solid Tumor	Phase 1	DK	Roche Holding AG	04 May 2020
Metastatic Solid Tumor	Phase 1	ES	Roche Holding AG	04 May 2020

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