SUZHOU, China—In a first-ever global proof-of-concept study carried out as a collaboration between the two companies, CStone Pharmaceuticals and Bayer HealthCare LLC have agreed to a global clinical collaboration to evaluate the safety, tolerability, pharmacokinetics (PK) and antitumor activity of CStone’s PD-L1 monoclonal antibody CS1001 in combination with Bayer’s regorafenib as a treatment for multiple cancers including gastric cancer.
Under the terms of the deal, CStone will be the study sponsor and Bayer will provide regorafenib, an oral multi-kinase inhibitor (targeting VEGFR, FGFR, CSF1R, etc.), throughout the clinical trial program.
“At present, patients with advanced gastric cancer lack safe and effective therapies,” noted Prof. Lin Shen, vice president at the Peking University Cancer Hospital. “Preclinical and clinical evidence suggest that the combination of PD-1/PD-L1 antibodies with multi-kinase inhibitors that target VEGFR can induce significant synergistic antitumor effects. We hope this combination therapy can provide a new treatment option for patients suffering from gastric cancer and other serious malignancies.”
CStone describes CS1001 as one of its “backbone immuno-oncology pipeline candidates,” saying that it has demonstrated that it is well tolerated and has promising antitumor activities across a variety of tumor types in clinical studies. Currently, CS1001 is being evaluated in seven clinical trials, including five pivotal trials.
Specifically, CS1001 has completed a Phase 1 dose-escalation study in China and has demonstrated promising anticancer activity and good tolerance. It is currently being evaluated in multiple clinical trials, including a bridging Phase 1 trial in the United States, a multi-arm Phase 1b study, two pivotal Phase 2 studies, and three Phase 3 studies in China in various cancer types, respectively. It has not yet been approved by any health authority for marketing.
In early June, during a poster presentation at the 2019 American Society for Clinical Oncology Annual Meeting, CStone shared data on CS1001-101 from a Phase 1a/1b open-label, multiple-dose, dose-escalation and expansion study assessing the safety, tolerability, pharmacokinetics and antitumor efficacy of the candidate in patients with advanced solid tumors or lymphomas. The trial reportedly indicates that CS1001 is well tolerated, with an expected pharmacokinetics profile and durable anti-tumor activities observed in a number of solid tumors and lymphomas.
As of Nov. 30, 2018, in the Phase 1a study, a total of 29 patients were enrolled and were administered with CS1001 at several escalating doses from 3 mg/kg all the way up to 40 mg/kg, as well as a 1,200 mg flat dose. The median treatment duration for all patients was 126 days. Nine patients remained on treatment as of data cutoff. Of the 29 patients enrolled, seven patients showed partial response, with an overall response rate of 24 percent (six patients are still on treatment).
“We are very pleased that Bayer has chosen CStone as its partner and recognizes CS1001’s potential,” said Dr. Frank Jiang, CStone chairman and CEO. “We hope, by complementing our two companies’ pipelines via this combination therapy, that we can develop better cancer treatments for patients. In addition, this collaboration will be a big step forward for CStone’s global strategy when we generate positive data.”
For its part, regorafenib is approved in more than 90 countries for the treatment of metastatic colorectal cancer and metastatic gastrointestinal stromal tumors, as well as in more than 80 countries for the second-line treatment of advanced hepatocellular carcinoma.
“Combining multi-kinase inhibitors, such as regorafenib, with checkpoint inhibitors is a rising trend in cancer therapy in order to find new solutions for the many treatment gaps that still remain for patients,” explained Dr. Scott Z. Fields, senior vice president and head of oncology development at Bayer’s Pharmaceutical Division. “We look forward to collaborating with CStone, an innovative biopharmaceutical company, and exploring regorafenib’s potential.”
Regorafenib is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumor angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF), metastasis (VEGFR3, PDGFR, FGFR) and tumor immunity (CSF1R). It is approved under the brand name Stivarga. Regorafenib was developed by Bayer, but in 2011, the company entered into an agreement with Onyx, now an Amgen subsidiary, under which Onyx receives a royalty on all global net sales of regorafenib in oncology.