spartalizumab (PDR001)

P1, N=98, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: May 2025 --> Dec 2024

P1, N=122, Terminated, Novartis Pharmaceuticals | Trial completion date: Jan 2025 --> Sep 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2025 --> Sep 2024; The decision of early termination was made due to business reasons, and was not based on any safety concerns for any of the treatment combinations.

P2, N=4, Terminated, M.D. Anderson Cancer Center | Completed --> Terminated; Study stopped due to slow enrollment

The combination of spartalizumab and PDC, with or without canakinumab, was well tolerated across treatment groups. The antitumor activity across treatment groups was comparable with that of pembrolizumab and pemetrexed combination. Canakinumab did not appear to improve the antitumor activity when combined with spartalizumab, pemetrexed and cisplatin.

Our results suggest that STING agonists may be able to work indirectly in MCC via signaling through immune and stromal cells in the TME, and may not necessarily need STING expression in the cancer cells. This approach may be particularly effective in tumors that are already infiltrated by inflammatory cells in the TME but are evading immune detection via HLA-I downregulation.

P3, N=569, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

P1, N=98, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2024 --> May 2025 | Trial primary completion date: Dec 2024 --> May 2025

P1, N=185, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

P1, N=122, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2024 --> Jan 2025 | Trial primary completion date: Oct 2024 --> Jan 2025

Sabatolimab plus spartalizumab was well tolerated in patients with advanced/metastatic melanoma or NSCLC who had progressed following antiprogrammed death-1/antiprogrammed death-ligand 1 treatment. Limited antitumour activity was observed. The tolerability of sabatolimab administration supports the potential to explore treatment with sabatolimab in various combination regimens and across a spectrum of tumour types.

P1, N=241, Completed, Novartis Pharmaceuticals | Phase classification: P1b --> P1

P2, N=70, Recruiting, Novartis Pharmaceuticals | Trial primary completion date: Sep 2027 --> Feb 2028

P1, N=98, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2024 --> Dec 2024

Patients with treatment-naïve advanced pancreatic ductal adenocarcinoma (n=10) were treated with canakinumab, a high-affinity monoclonal human anti-interleukin-1β (IL-1β), the PD-1 blocking antibody spartalizumab, and gemcitabine/n(ab)paclitaxel. Within the tumor we observed few changes in suppressive myeloid-cell populations or activated T cells as assessed by single-cell transcriptional profiling or multiplex immunofluorescence, although increases in CD8+ T cells suggest that improvements in the tumor immune microenvironment might be revealed by a larger study. Overall, the data indicate that exposure to PD-1 and IL-1β blockade induced a modest reactivation of peripheral CD8+ T cells and decreased circulating monocytic MDSCs; however, these changes did not lead to similarly uniform alterations in the tumor microenvironment.

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

Spartalizumab showed promising activity with a manageable safety profile, indicating its potential as a new treatment option for patients with refractory ESCC. The trial was registered at ClinicalTrials.gov under the identifier NCT03785496.

P1, N=121, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2034 --> Apr 2030 | Trial primary completion date: Jan 2034 --> Apr 2030

P1, N=121, Recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2030 --> Jan 2034 | Trial primary completion date: Mar 2030 --> Jan 2034

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.

However, gating criteria for efficacy were not met for expansion beyond 80 patients in phase II and the sponsor did not continue development of the combination of spartalizumab and lacnotuzumab for oncology indications. The potential signal of activity in pancreatic cancer should be further explored.

P2, N=70, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2028 --> Feb 2028

In patients with treatment-refractory GIST, PDR001 in combination with imatinib was generally tolerable, but it was not effective.

P1, N=98, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: May 2025 --> Sep 2024 | Trial primary completion date: May 2025 --> Sep 2024

P1/2, N=59, Recruiting, University Hospital, Bordeaux | Not yet recruiting --> Recruiting

P3, N=569, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2024 --> Aug 2024

P1, N=40, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jul 2025 --> Feb 2025 | Trial primary completion date: Jul 2025 --> Feb 2025

P1, N=122, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: May 2024 --> Sep 2024 | Trial primary completion date: May 2024 --> Sep 2024

P1, N=98, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Apr 2024 --> May 2025 | Trial primary completion date: Apr 2024 --> May 2025

P1, N=154, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2024 --> Nov 2024 | Trial primary completion date: Jun 2024 --> Nov 2024

P1, N=122, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business reasons

Pembrolizumab or spartalizumab can be utilized in patients with high TMB anaplastic thyroid cancer, obtaining better response rates particular in patients with high PD-L1 expression. Future research is needed to evaluate the potential role of immunohistochemical biomarkers, such as PD-1/PD-L1 and TMB, as predictors for response to immunotherapy. Furthermore, randomized prospective studies could provide more robust data on the efficacy and side effects of ICIs.

Our results show that in BRAFm-ATC, addition of pembrolizumab to dabrafenib/trametinib may significantly prolong survival. Surgical resection of the primary tumor after initial BRAF-targeted therapy in selected patients may provide further survival benefit. However, conclusions are limited by the retrospective nature of the study. Additional prospective data are needed to confirm this observation.

P1, N=60, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business decision and not due to any safety concerns

P1, N=16, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

P2, N=34, Recruiting, Centre Hospitalier Universitaire de Besancon | Phase classification: P2a --> P2 | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Nov 2023 --> Jun 2025

P1, N=40, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=180 --> 40

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

Naporafenib, with or without spartalizumab, showed an acceptable safety profile, pharmacodynamic activity and limited antitumor activity. Additional naporafenib combination therapies are currently under investigation.

NIZ985 was well tolerated in the single-agent and NIZ985/spartalizumab regimens. The RDE was established at 1 µg/kg TIW. Antitumor activity of the combination was observed against tumor types known to have a poor response to ICIs.

P3, N=569, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2023 --> Mar 2024

P2, N=4, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Feb 2024 --> Oct 2023 | Trial primary completion date: Feb 2024 --> Oct 2023

P1, N=77, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business reasons