simlukafusp alfa (RG7461)

P1/2, N=340, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Oct 2026 --> Jan 2025 | Trial primary completion date: Oct 2025 --> Jan 2025

The 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).].

FAP-IL2v plus atezolizumab is clinically active and has manageable safety in patients with recurrent and/or metastatic cervical SCC.

P2; FAP-IL2v plus atezolizumab demonstrated clinical activity and was tolerable in patients with previously treated esophageal SCC.

FAP-IL2v had a manageable safety profile and showed initial signs of antitumor activity in advanced/metastatic solid tumors.

P1/2, N=340, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

P1/2, N=340, Recruiting, Hoffmann-La Roche | Trial completion date: Jun 2024 --> Oct 2026 | Trial primary completion date: Jun 2024 --> Oct 2025

P2, N=256, Terminated, Hoffmann-La Roche | Completed --> Terminated; The Sponsor discontinued the development of Simlukafusp alfa due to portfolio prioritization, not due to any safety, efficacy, or quality issues.

P1a/1b, N=134, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

P1, N=83, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

P1/2, N=290, Recruiting, Hoffmann-La Roche | Active, not recruiting --> Recruiting

P2, N=256, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

P1/2, N=290, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Nov 2022 --> Jun 2024 | Trial primary completion date: Nov 2022 --> Jun 2024

P1a/1b, N=134, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022

P1b, N=69, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

P1/2, N=290, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

SIM in combination with ATZ demonstrated an acceptable safety profile in pts with R/M cervical SCC . The anti-tumor activity compares favorably to the approved PD-1 inhibitors in this setting and supports further exploration of IL-2v and checkpoint inhibition in this patient population of high unmet medical need.

The combination of SIM with ATZ ± BEV was feasible with an acceptable safety profile . Clinical activity was more favorable for the triplet among the study Arms, but comparable to the ATZ + BEV combination in the IMmotion151 (Rini B, et al 2019) . Observed pharmacodynamic findings were consistent with the expected effects.

P1/2, N=290, Recruiting, Hoffmann-La Roche | Trial completion date: Nov 2021 --> Nov 2022 | Trial primary completion date: Nov 2021 --> Nov 2022

Moreover, lymphoma-FRCs upregulated expression of inhibitory PD-1 ligands that reduced the anti-tumor cytolytic activity of CD8+ T cells, a T cell bispecific antibody (CD20-TCB, glofitamab) and anti-CD19 CAR T cells in our coculture models.To overcome the immunosuppressive activity of DLBCL-FRCs, we investigated the use of CD20-TCB in combination with stroma-targeting immunocytokine fusion protein drug (FAP-IL2v, RG7461) or costimulatory fusion protein (FAP-4-1BBL, RG7827). In addition, the ability of immune- /stroma- targeted combination immunotherapy to trigger anti-tumor activity and CD8+ T cell retention within the FRC-TME was demonstrated using 3D precision-cut lymph node slice-based organotypic cultures of DLBCL and other B cell malignancies.In conclusion our data reveal that lymphoma cells actively reprogram FRCs that acquire altered immunoregulatory function which prevents effective T cell motility and suppresses the anti-tumor function of cytolytic T cells. Importantly, we demonstrate that combination immunotherapy incorporating fibroblast-targeting fusion proteins could effectively recover anti-tumor T cell activity.

P1a/1b, N=134, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

P1, N=83, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | N=150 --> 83

P1a/1b; N=150; Recruiting; Sponsor: Hoffmann-La Roche; Trial completion date: May 2020 --> Dec 2021; Trial primary completion date: May 2020 --> Dec 2021

P1b, N=69, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Dec 2020 --> Mar 2021 | Trial primary completion date: Dec 2020 --> Mar 2021

P1, N=150, Recruiting, Hoffmann-La Roche | Trial primary completion date: Apr 2020 --> Apr 2022

P1/2 | "Control treatment was mFOLFOX6 or gemcitabine plus nab-paclitaxel (Gem/nab-pac). Legal entity responsible for the study The authors. Funding F. Hoffmann-La Roche, Ltd."

P1/2; Trial completion date: Feb 2022 --> Nov 2021 | Trial primary completion date: Feb 2022 --> Nov 2021

P1; N=150; Recruiting; Sponsor: Hoffmann-La Roche; Trial completion date: Dec 2020 --> Jan 2022

P1b; Trial primary completion date: Sep 2020 --> Dec 2020

P1/2; Trial completion date: Sep 2020 --> Feb 2022 | Trial primary completion date: Nov 2019 --> Feb 2022

P1, N=150, Recruiting, Hoffmann-La Roche | N=40 --> 150

P1b; N=350 --> 69

P2; N=280; Recruiting; Sponsor: Hoffmann-La Roche; Trial completion date: Dec 2020 --> Jan 2022; Trial primary completion date: Feb 2019 --> Jan 2022

P1b; Recruiting --> Active, not recruiting | Trial completion date: Apr 2021 --> Dec 2020

P1, N=40, Recruiting, Hoffmann-La Roche | Not yet recruiting --> Recruiting

P1, N=40, Not yet recruiting, Hoffmann-La Roche

P1a/1b, N=205, Recruiting, Hoffmann-La Roche | Trial completion date: Jul 2019 --> May 2020 | Trial primary completion date: Jul 2019 --> May 2020

P2; N=360; Recruiting; Sponsor: Hoffmann-La Roche; N=240 --> 360

P1b; Trial completion date: Sep 2020 --> Jul 2021

P1/2; Trial completion date: Apr 2020 --> Sep 2020

P2; N=240; Recruiting; Sponsor: Hoffmann-La Roche; N=40 --> 240

P1b; N=190 --> 270