How does CS1001 work?
An immunotherapy, CS1001 contains an antibody against programmed death-ligand 1, known as PD-L1.
PD-L1 is a protein that is normally found on the surface of healthy cells. It binds to receptor proteins found on immune cells called T-cells and signals to the T-cell that the cell is healthy.
Cells that are infected or cancerous normally stop producing PD-L1. Therefore, T-cells are alerted of the problem and target these cells for destruction. However, some types of cancer cells have “learned” to produce large quantities of PD-L1 to avoid the T-cell’s response. The increase in PD-L1 signals to the T-cell that all is well, and that the immune system does not need to target these cells.
CS1001 contains an antibody against PD-L1 that recognizes and binds to it. It prevents PD-L1 from binding to receptors on T-cells. Without being able to stop the T-cells, the cancerous cells should become vulnerable to the immune system’s attack.
Because CS1001 is an antibody, it must be injected or infused, and cannot be taken by mouth.
Cancer patients should be tested for PD-L1 levels to determine whether this type of immunotherapy might be effective in treating their cancer.
CS1001 in clinical trials
Phase 1a clinical trials have shown that CS1001 is well-tolerated and leads to partial remissions in multiple tumor types. These findings were presented at the European Society for Medical Oncology (ESMO) 2018 meeting.
CS1001 combined with chemotherapy also was found to be safe and effective in treating advanced solid tumors and lymphomas in Phase 1b clinical trials. These findings were presented at the ESMO 2019 meeting.
A Phase 1/2 clinical trial (NCT04200404) in Australia is currently recruiting 128 people with advanced or refractory cancers. CStone plans a collaborative assessment of the safety, tolerability, pharmacokinetic profile, and treatment effect of CS1001 in combination with regorafenib. In the first half of the trial, participants will receive escalating doses of CS1001 in combination with regorafenib. In the second half, patients will be divided into treatment groups based on their cancer type. The primary outcome measure will be the number of adverse events and dose-limiting toxicity. CStone is collaborating with Bayer for this clinical trial.
An open-label, dose-escalating study to assess the safety and efficacy of CS1001 is now recruiting participants in Texas. In the Phase 1 clinical trial (NCT03744403), a total of 20 patients with advanced solid tumors will receive increasing doses of CS1001. The primary outcome measure will be the number of patients with adverse events.
Several new studies in China also are now enrolling participants with various types of cancer to further test the investigational therapy.
A Phase 3 clinical trial (NCT03728556) in Guangzhou is recruiting patients with non-small cell lung cancer to assess the safety and efficacy of CS1001. An estimated 402 participants with stage 3 cancer will be randomly assigned to receive either CS1001 or a placebo every three weeks for up to two years. The primary outcome measure will be progression-free survival.
Individuals with advanced solid tumors are being recruited at two locations — in Beijing and Shanghai — for a Phase 1a/1b clinical trial (NCT03312842). This study will test the safety, tolerability, pharmacokinetics (movement in the body), and anti-tumor activity of CS1001 in 28o patients. In the first part of the trial, participants will receive increasing doses of CS1001. In the second half, the patients will be divided into groups based on the type of cancer they have. The goal of the study is to determine safety and tolerability, with the secondary goal of determining the maximum safe dose of CS1001.
The safety and efficacy of CS1001 in people with relapsed or refractory extranodal natural killer/ T-cell lymphoma will be tested in a Phase 2 clinical trial (NCT03595657) now recruiting in Guangzhou. In this trial, which is recruiting 80 patients, ages 18 to 17, the primary outcome measure will be the objective response rate. Participants will receive CS1001 every three weeks.
Another Phase 2 clinical trial (NCT03505996) is recruiting 80 patients in Beijing with refractory Hodgkin’s lymphoma to also test the safety and efficacy of CS1001. The therapy will be given every three weeks. The primary outcome measure will be the objective response rate — a reduction of tumor size.
A total 480 people with stage 4 non-small cell lung cancer are being recruited for a Phase 3 clinical trial (NCT03789604) in Shanghai. This trial will assess the safety and efficacy of CS1001 in patients treated with platinum-based chemotherapies. Participants will receive CS1001 or placebo in combination with carboplatin, pemetrexed, or paclitaxel for up to two years. Progression-free survival is the primary outcome measure.
A Phase 3 clinical trial (NCT04187352) is recruiting 420 patients in Shanghai to assess the efficacy and safety of CS1001 or placebo in combination with fluorouracil and cisplatin — two chemotherapy treatments — in treating esophageal squamous cell carcinoma. Patients will be randomly assigned to receive either CS1001 or placebo in combination with fluorouracil and cisplatin. The primary outcome measure will be progression-free survival.
People with gastric adenocarcinoma are being recruited for a Phase 3 clinical trial (NCT03802591) in Beijing that will test the safety and efficacy of CS1001 versus a placebo in combination with other therapies. A total of 480 participants will be randomly assigned to receive either CS1001 or placebo in combination with oxaliplatin and capecitabine. Progression-free survival and overall survival will be the primary outcome measure.
One trial that is not yet recruiting patients will test CS1001 in people with hepatocellular carcinoma, a form of liver cancer. The Phase 1/2 clinical trial (NCT04194801) will evaluate the safety, tolerability, pharmacokinetics, and efficacy of CS1001 in combination with BLU554 (CS3008), another experimental therapy from CStone therapy. The primary outcome measure will be dose-limiting toxicity and overall response rate.
Last updated: Jan. 28, 2020
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