nisevokitug (NIS793)

P1/2, N=45, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

P3, N=511, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

P1, N=4, Terminated, Colin D. Weekes, M.D., PhD | N=50 --> 4 | Trial completion date: May 2025 --> Jul 2023 | Recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Jul 2023; NIS793 is no longer being developed

P2, N=204, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: May 2024 --> Sep 2024

P1, N=33, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business reasons

P2, N=164, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; The study was early terminated following the NIS793 treatment halt and urgent safety measure issued in July 2023, as the continued evaluation of Standard of Care alone will not support the original purpose of this phase 2 clinical trial.

P2, N=204, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Sep 2024 --> May 2024

P2, N=205, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: May 2024 --> Sep 2024

P1/2, N=45, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2024 --> Jul 2024

P3, N=511, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2026 --> Jun 2024 | Trial primary completion date: Jan 2026 --> Jun 2024

In patients with advanced solid tumors, proof of mechanism of NIS793 is supported by evidence of target engagement and TGF-β pathway inhibition.

P2, N=8, Terminated, Kimberly Perez, MD | Trial completion date: Dec 2027 --> Oct 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2027 --> Aug 2023; Novartis, the drug manufacturer of NIS793, notified Dana Farber Cancer Institute that they are stopping all clinical development of NIS793 in pancreatic cancer, effective immediately.

P1, N=33, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=90 --> 33 | Trial completion date: Sep 2024 --> May 2024 | Trial primary completion date: Sep 2024 --> May 2024

P2, N=151, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Nov 2023 --> Apr 2024 | Trial primary completion date: Nov 2023 --> Apr 2024

TGFβ regulates pancreatic cancer cell plasticity between classical and basal cell states. TGFβ blockade in orthotropic models of pancreatic cancer enhances sensitivity to chemotherapy by promoting a classical malignant cell state. This study provides scientific rationale for evaluation of NIS793 with either FOLFIRINOX or gemcitabine/n(ab)paclitaxel chemotherapy backbone in the clinical setting and supports the concept of manipulating cancer cell plasticity to increase the efficacy of combination therapy regimens.

P2, N=268, Recruiting, Novartis Pharmaceuticals | Trial primary completion date: Sep 2024 --> May 2024

P2, N=161, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

Pts are treated with NIS793 (Day [D]1 ± D15; 2100 mg) + SOC (D1 + D15; bevacizumab [5 mg/kg] + FOLFIRI/mFOLFOX6) +/- tislelizumab (D1; 300 mg), or SOC alone...The daNIS-3 study started on November 15, 2021, and plans to recruit approximately 266 pts from 77 sites across 19 countries. Clinical trial information: NCT04952753.

The study is funded by Novartis. Clinical trial information: NCT04390763.

No abstract available

No abstract available

No abstract available

The first pt was treated on October 22, 2020. Enrollment for the randomized part of the study started on August 09, 2021.

This study is ongoing and will enroll pts from approximately 149 sites across 28 countries. The first pt was treated on October 20, 2021.

P2, N=161, Recruiting, Novartis Pharmaceuticals | Trial completion date: May 2023 --> Oct 2023 | Trial primary completion date: May 2023 --> Oct 2023

Currently, a limited number of small molecular inhibitor and monoclonal antibody candidates that target TGF-β are in clinical development in combination with the following immune checkpoint inhibitors: SRK 181, an antibody inhibiting the activation of latent TGF-β1; NIS 793, a monoclonal antibody targeting TGF-β; and SHR 1701, a fusion protein consisting of an anti-PD-L1 monoclonal antibody fused with the extracellular domain of human TGF-β receptor II. Several small molecular inhibitors are also in development and are briefly reviewed: LY364947, a pyrazole-based small molecular inhibitor of the serine-threonine kinase activity of TGFβRI; SB-431542, an inhibitor targeting several TGF-β superfamily Type I activin receptor-like kinases as well as TGF-β1-induced nuclear Smad3 localization; and galunisertib, an oral small molecular inhibitor of the TGFβRI kinase. One of the most advanced agents in this area is bintrafusp alfa, a bifunctional fusion protein composed of the extracellular domain of TGF-β receptor II fused to a human IgG1 mAb blocking PD-L1. Bintrafusp alfa is currently in advanced clinical development and as an agent in this space with the most clinical experience, is a focused highlight of this review.

P2, N=161, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2023 --> May 2023 | Trial primary completion date: Jan 2023 --> May 2023

Methods ADORE (NCT04097821) is a 3-part, open-label, multicenter, phase 1/2, platform study that will assess the safety and efficacy of RUX in combination with 5 novel compounds for the treatment of MF: siremadlin (HDM2 inhibitor), crizanlizumab (anti-P-selectin antibody), sabatolimab (anti-TIM-3 antibody), rineterkib (ERK1/2 inhibitor) and NIS793 (anti-TGFβ antibody) ( Figure ). Assuming all five combination treatments enter Part 2 and one combination treatment is expanded in Part 3, a total of 240 patients are planned to be enrolled. The study is open for enrolling into Part 1.

P1, N=120, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

Data showing target engagement and TGF-β pathway inhibition supported the proof of mechanism of NIS793 . The RDE of the combination was established and well tolerated in pts with advanced solid tumors.

This study is ongoing and will enroll pts from 30 sites across 15 countries . The first pt was treated on October 22, 2020.

P1, N=120, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=220 --> 120

P2, N=156, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

P2, N=156, Not yet recruiting, Novartis Pharmaceuticals

P1, N=154, Not yet recruiting, Novartis Pharmaceuticals