Cantargia presents new data at SITC 2022 supporting nadunolimab’s promising antitumor clinical efficacy
Data shows nadunolimab dual mechanism potently reduces levels of tumor-promoting molecules
Cantargia (Cantargia AB; Nasdaq Stockholm: CANTA) today reported new data providing further insights to the mechanisms underlying the antitumor activity of the IL1RAP-binding antibody nadunolimab (CAN04). In a model of the pancreatic cancer (PDAC) microenvironment, nadunolimab potently reduced levels of various tumor-promoting molecules, in sharp contrast to an anti-IL-1β antibody which showed no such effects. PDAC and non-small cell lung cancer (NSCLC) patients treated with nadunolimab and chemotherapy showed reductions in the same molecules. The data will be presented in a poster session at the 37th Annual SITC Meeting 2022 (SITC 2022), held in Boston, November 8-12, 2022.
“The results provide new and exciting insights into the unique anti-tumor properties of nadunolimab, and further illustrate the advantages of its dual action properties. The findings strongly support the upcoming randomized clinical trials of nadunolimab,” said Göran Forsberg, CEO of Cantargia.
Both IL-1α and IL-1β signal via IL1RAP and contribute to tumor progression by triggering the release of molecules such as CXCL1 and CXCL5, which stimulate recruitment of immune suppressive cells to the tumor. The data reported at SITC 2022 confirm that both IL-1α and IL-1β cause a release of CXCL1, CXCL5 and additional related markers by human blood cells and cancer-associated fibroblasts (CAF). Furthermore, the data show that IL1RAP blockade by nadunolimab reduces these effects.
In the presence of PDAC cells, tumor-supporting CAF also release CXCL1, CXCL5 and other markers, and these are similarly attenuated by nadunolimab but not an anti-IL-1β antibody. The effect is highly relevant to nadunolimab’s activity in the clinic: in blood samples from PDAC and NSCLC patients treated with nadunolimab and chemotherapy in the phase I/IIa trial CANFOUR, levels of CXCL1 and CXCL5 were reduced compared to samples collected prior to therapy. Increased levels of CXCL1 and CXCL5 are linked to poor patient prognosis. Preclinical studies by others have also shown that antibody targeting of CXCL1 or CXCL5 results in antitumor efficacy, and blockade of these signaling pathways are evaluated in clinical trials of cancer.
The findings support the promising clinical interim efficacy data presented recently at the ASCO Annual Meeting 2022. In over 100 patients evaluated in the CANFOUR trial, nadunolimab in combination with chemotherapy results in higher efficacy than historical controls for chemotherapy alone. Cantargia is preparing the next steps in the late-stage clinical development of nadunolimab in PDAC and NSCLC. Nadunolimab will be included in the pivotal phase II/III clinical trial Precision PromiseSM, designed by Pancreatic Cancer Action Network (PanCAN), and a randomized trial in NSCLC is also planned for 2023.
The results will be presented at SITC 2022 in a poster, details of which can be found below. The poster will be made available on Cantargia’s webpage (https://cantargia.com/en/research-development/publications) after the presentation on 10 November.
Abstract number: 145
Abstract category: Biomarkers, Immune Monitoring and Novel Technologies
Abstract title: Nadunolimab inhibits IL-1α/β-induced CXCR1/2 ligand expression and reduces serum levels of CXCL1 and CXCL5 in NSCLC and PDAC patients
Presenter: Dr. Camilla Rydberg Millrud
For further information, please contact
Göran Forsberg, CEO
Telephone: +46 (0)46-275 62 60
E-mail: goran.forsberg@cantargia.com
This is information that Cantargia AB is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 14.00 CET on 7 November 2022.
About Cantargia
Cantargia AB (publ), reg. no. 556791-6019, is a biotechnology company that develops antibody-based treatments for life-threatening diseases and has established a platform based on the protein IL1RAP, involved in a number of cancer forms and inflammatory diseases. The main project, the antibody nadunolimab, is being studied clinically in combination with chemotherapy or immune therapy with a primary focus on non-small cell lung cancer and pancreatic cancer. Positive interim data from the combination with chemotherapy indicate stronger efficacy than would be expected from chemotherapy alone. Cantargia’s second project, the antibody CAN10, addresses treatment of serious autoimmune/inflammatory diseases, with initial focus on systemic sclerosis and myocarditis.
Cantargia is listed on Nasdaq Stockholm (ticker: CANTA). More information about Cantargia is available at www.cantargia.com.
About nadunolimab (CAN04)
The antibody CAN04 binds strongly to its target IL1RAP and functions by inducing ADCC and blocking IL-1α and IL-1β signaling. Thereby, CAN04 can counteract the contribution of the IL-1 system to the immune suppressive tumor microenvironment and development of resistance to chemotherapy. CAN04 is investigated in multiple ongoing clinical trials. In the phase I/IIa study CANFOUR, first line combination therapy is investigated with standard chemotherapies in patients with PDAC (gemcitabine/nab-paclitaxel) and patients with NSCLC (cisplatin/gemcitabine) (NCT03267316). Positive interim data for the combination therapies show durable responses in 73 patients with PDAC, resulting in median iPFS of 7.2 months and median survival of 12.7 months. Stronger efficacy was also observed in 30 NSCLC patients with median PFS of 6.8 months. A response rate of 53% was achieved, with even higher responses in non-squamous NSCLC patients previously treated with pembrolizumab. These results show stronger efficacy than expected from chemotherapy alone. CAN04 is investigated with chemotherapy also in the phase I study CAPAFOUR, with the FOLFIRINOX regimen for first line treatment of metastatic PDAC (NCT04990037), and in two further clinical studies, CESTAFOUR (NCT05116891) and TRIFOUR (NCT05181462), in additional forms of cancer, including biliary tact cancer, colorectal cancer and triple negative breast cancer. CAN04 is also evaluated with the checkpoint inhibitor pembrolizumab, with or without chemotherapy, in the phase I study CIRIFOUR (NCT04452214).