First Patient Dosed in Proof-of-concept Study of CS1001 Plus Stivarga for Advanced Solid Tumors

First Patient Dosed in Proof-of-concept Study of CS1001 Plus Stivarga for Advanced Solid Tumors

CStone Pharmaceuticals has dosed the first patient in a clinical trial designed to evaluate CS1001, the company’s experimental PD-L1 inhibitor, in combination with Bayer’s Stivarga (regorafenib), for the treatment of advanced solid tumors.

The Phase 1b/2 trial (NCT04200404), so far recruiting participants at the Ashford Cancer Centre Research in Australia, is the first global proof-of-concept study conducted as part of the collaboration between CStone and Bayer, which was announced in June 2019.

It is designed to include 138 participants with advanced or refractory tumors, including stomach cancer, and to determine the safety, tolerability, and pharmacokinetics (how the treatment behaves in the body in its absorption, distribution, metabolism, and excretion), as well as the effectiveness of CS1001 in combination with Stivarga.

The trial will be conducted in two parts: in the Phase 1b part, patients will receive ascending doses of CS1001 (injected into the vein once every four weeks) and Stivarga (given orally once daily for the first three weeks of each four-week cycle). The goal is to determine the optimal dose for further testing.

In Phase 2, patients will be assigned to different groups based on their tumor type and treated with the recommended dose identified in part one.

“Our collaboration with Bayer in this clinical program marks an important milestone in the implementation of CStone’s global strategy. I am very pleased that the first patient has been dosed in this combination study,” Frank Jiang, MD, PhD, chairman and CEO of CStone, said in a press release.

“We hope this clinical program will strengthen CStone’s pipeline, and above all demonstrate the utility of this combination in improving the clinical outcomes for cancer patients who lack effective treatments,” added Jiang.

CS1001 is a monoclonal antibody that targets PD-L1, a protein produced by cancer cells to avoid immune system attacks. PD-L1 binds to its receptor PD-1 in immune T-cells — those that would normally attack cancer cells — and this binding essentially suppresses the activity of such immune cells.

The experimental treatment belongs to a class of cancer therapies called immune checkpoint inhibitors. Because it is a fully human antibody, CS1001 mirrors natural human antibodies, which can reduce the risk of harmful immune side effects associated with biologic therapies, and be safer for patients.

CS1001 is being evaluated across a number of clinical trials, including one Phase 1 study (NCT03744403) in the United States. The other trials are being conducted in China and include a Phase 1b study for solid tumors (NCT03312842), two Phase 2 registrational studies in lymphoma (NCT03595657 and NCT03505996), and four Phase 3 studies in lung (NCT03728556 and NCT03789604), esophagus (NCT04187352), and stomach (NCT03802591) cancers.

Results from the Phase 1b study in China have already demonstrated that CS1001 is well-tolerated and has promising anti-tumor activities across multiple cancers. In a rare lymphoma called extranodal natural killer (NK)/T-cell lymphoma, the treatment also reduced tumor burden in 41% of patients, most of whom achieved a full remission of their cancers.

Stivarga is an oral inhibitor of multiple kinases, such as EGFR, FGFR, and CSF1R, that are involved in tumor development, in cancer spread to distant regions of the body, and in maintenance of the tumor microenvironment.

It is approved in 90 countries, including the U.S. and China, for people with advanced colorectal cancer, gastrointestinal cancer, and liver cancer.

Preclinical studies have suggested that targeted therapies, such as Stivagra, can increase the efficacy of immune checkpoint inhibitors, such as CS1001, in certain solid tumors by regulating the tumor immune microenvironment.

“Preclinical studies in animal models have shown enhanced antitumor activity by the CS1001 plus regorafenib combination, lending evidential support to the design of this proof-of-concept study. In addition, a range of global studies of similar immuno-combination therapies have generated promising results in advanced or metastatic solid tumors,” said Archie Tse, MD, PhD, chief translational medicine officer at CStone.

“We hope results from this trial will further validate the combination of multi-kinase inhibitors and immunotherapy in select tumors,” added Tse.