Cosibelimab Shows Signs of Anti-cancer Activity Against Multiple Tumor Types in Phase 1 Trial

Treatment with Checkpoint Therapeutics’ investigational immunotherapy Cosibelimab supports a positive anti-cancer response in approximately 28% of patients with advanced solid tumors, interim results from an ongoing Phase 1 trial show.

In particular, the therapy showed greater potential to treat those with non-small-cell lung carcinoma and cutaneous squamous cell carcinoma, who showed an objective response rate above 40%.

“We are excited by the compelling efficacy demonstrated in the interim data of cosibelimab … as well as the strikingly high rate of patients with target lesion reductions across diverse tumor types,” James F. Oliviero, president and CEO of Checkpoint Therapeutics, said in a press release.

“The goal of this [Phase 1] study was to demonstrate that cosibelimab has a safety and efficacy profile consistent with marketed PD-(L)1 inhibitors, so we are thrilled to report these strong results for our potentially differentiated anti-PD-L1 antibody,” he added.

Cosibelimab, formerly named CK-301, is an investigational monoclonal antibody that binds to the immune checkpoint PD-L1, blocking its interaction with the programmed death receptor-1 (PD-1) and B7.1 receptors, and unleashing a full-blown anti-cancer immune response.

The antibody was designed to have high stability and long circulating half-life, while holding enhanced anti-cancer activity.  An additional benefit of cosibelimab compared to other anti-PD-1 and anti-PD-L1 immunotherapies is its capacity to directly induce the death of PD-L1-positive tumors by recruiting immune cells to their vicinity — a mechanism called antibody-dependent cell-mediated cytotoxicity (ADCC).

The ongoing Phase 1 study (NCT03212404) was planned to evaluate cosibelimab’s safety, efficacy, and metabolism inside the body (pharmacokinetics) when administrated in ascending doses to patients with advanced cancers who had not previously been treated with this type of immunotherapy.

The trial is being conducted across 20 clinical sites in Australia, New Zealand, Russia, and Thailand. It is recruiting participants with diverse solid and blood cancers.

Patient enrollment is open to those with endometrial cancer, with both microsatellite stable and highly instable tumors — those presenting a high frequency of mutations in their DNA — and for those with mismatch repair deficient (dMMR) colorectal tumors. The trial is also enrolling patients with cutaneous squamous cell carcinoma.

As of April, 65 patients were included in the dose escalation study to identify the safest and most efficacious dose of cosibelimab. Forty-two of those remain on treatment for a period of one to more than 17 months.

Participants who complete this first part of the trial will then receive a fixed dose of cosibelimab  (800 mg) administered intravenously every two weeks.

Cosibelimab was found safe and well-tolerated with no dose-limiting toxicities being reported. Treatment-related adverse events were seen in 49% of the patients (32 of 65), the most common being rash and fatigue. Serious treatment-related adverse effects occurred in 8% of patients (5 of 65). These included anemia, lack of energy, hypertension, low calcium blood levels, and high blood pressure.

In a preliminary analysis, researchers measured how tumors responded to the therapy in 36 patients. Ten patients (28%) experienced tumor size reduction, as determined by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria. The disease was controlled — meaning the patient either improved or remained stable — in 75% of the cases (27 of 36 patients).

The best responses were seen in patients with non-small-cell lung carcinoma and with cutaneous squamous cell carcinoma, with an objective response rate of 42% and 43%, respectively, and a disease control rate of 83% and 86%.

In melanoma patients and in patients with other advanced cancers, including Hodgkin’s lymphoma and colorectal cancer, the objective response rate was 14% and 10%, respectively. More than half of them had stable disease, as shown by a disease control rate of 71% and 60%.

Median duration of response has not been reached. Researchers are following all the patients, with pending analysis of 17. Additional findings are set for presentation at future medical meetings.

Checkpoint Therapeutics hopes that the data generated from the trial will support the company’s requests for accelerated approval and Biologics License Application to the U.S. Food and Drug Administration.

“We look forward to continuing to enroll patients into potential registration-enabling cohorts in order to support one or more marketing application submissions based on this ongoing clinical trial,” Oliviero said.