Novartis Discontinues Development of NIS793 in Pancreatic Cancer

Novartis will discontinue the development of the anti-TGFß monoclonal antibody NIS793 for the treatment of patients with pancreatic cancer and other malignancies, according to a SEC filing from Xoma.¹

Enrollment for ongoing studies investigating NIS793 will cease; however, data will continue to be collected for these trials.

“NIS793 is an investigational compound. Efficacy and safety have not been established. There is no guarantee that NIS793 will become commercially available,” the filing read.

In July 2021, the FDA granted an orphan drug designation to NIS793 in combination with standard-of-care chemotherapy for the treatment of patients with pancreatic cancer.²

Previous data from a phase 1b trial (NCT02947165) showed that in patients with advanced solid tumors (n = 120) treated with NIS793 monotherapy or in combination with the PD-1 inhibitor spartalizumab (PDR001), the best overall response was a partial response in 3% of patients (n = 4).³ Additionally, 23% of patients (n = 28) experienced stable disease (SD), including 12 patients who had SD for more than 4 months. Fifty-nine percent of patients (n = 71), experienced progressive disease, and response was unknown for 14% of patients (n = 17).

The combination was well tolerated, and no dose-limiting toxicities were observed. Among patients treated with NIS793 plus spartalizumab (n = 109), the most common treatment-related adverse effects included skin rash (13%), pruritis (8%), and fatigue (8%).

NIS793 was under further investigation in the phase 2 daNIS-1 trial (NCT04390763), which was evaluating the combination of the anti-TGFß monoclonal antibody and standard-of-care chemotherapy with or without spartalizumab in the first-line treatment of patients with metastatic pancreatic ductal adenocarcinoma (PDAC).⁴

The randomized, placebo-controlled phase 3 daNIS-2 trial (NCT04935359) was examining NIS793 or placebo in combination with gemcitabine and nab-paclitaxel (Abraxane) for the first-line treatment of patients with metastatic PDAC.⁵

An ongoing phase 1 trial (NCT05417386) is evaluating the addition of NIS793 to FOLFIRINOX for the treatment of patients with metastatic pancreatic cancer.⁶

References

1. Form 8-K. Xoma. August 25, 2023. Accessed August 30, 2023. https://investors.xoma.com/sec-filings/all-sec-filings/content/0001193125-23-221604/0001193125-23-221604.pdf
2. Novartis receives FDA orphan drug designation for NIS793 in pancreatic cancer. News release. Novartis. July 27, 2021. Accessed August 30, 2023. https://www.novartis.com/news/novartis-receives-fda-orphan-drug-designation-nis793-pancreatic-cancer
3. Bauer TM, Lin CC, Greil R, et al. Phase Ib study of the anti-TGF-β monoclonal antibody (mAb) NIS793 combined with spartalizumab (PDR001), a PD-1 inhibitor, in patients (pts) with advanced solid tumors. J Clin Oncol. 2021;39(suppl 15):2509. doi:10.1200/JCO.2021.39.15_suppl.2509
4. Study of efficacy and safety of NIS793 (with and without spartalizumab) in combination with SOC chemotherapy in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) (daNIS-1). ClinicalTrials.gov. Updated August 29, 2023. Accessed August 30, 2023. https://clinicaltrials.gov/study/NCT04390763
5. Study of efficacy and safety of NIS793 in combination with standard of care (SOC) chemotherapy in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) - daNIS-2. ClinicalTrials.gov. Updated August 8, 2023. Accessed August 30, 2023. https://clinicaltrials.gov/study/NCT04935359
6. FOLFIRINOX + NIS793 in pancreatic cancer. ClinicalTrials.gov. Updated August 23, 2022. Accessed August 30, 2023. https://clinicaltrials.gov/study/NCT05417386