Phase 1 Trial Will Test CLN-978 in B-Cell NHL

A clinical trial will investigate a new subcutaneous drug for the treatment of certain patients with B-cell non-Hodgkin lymphoma.

The first patient received treatment in a phase 1 clinical trial investigating the novel agent CLN-978 for the treatment of relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL), according to a press release published by Cullinan Oncology, the manufacturer of the drug.

The first-in-human trial will evaluate the safety and tolerability of the subcutaneous (injected under the skin) drug, as well as how it moves through the body and how effective it is in treating cancer in adults with relapsed/refractory B-NHK who have no other Food and Drug Administration (FDA)-approved therapies.

“Despite recent advances in treating B-NHL, there remains significant unmet medical need, particularly among patients with relapsed/refractory disease,” said Dr. Jeffrey Jones, MBA, the chief medical officer at Cullinan Oncology, said in the press release.

According to the trial’s listing on ClinicalTrials.gov, researchers plan to enroll approximately 90 patients on the study, which will be conducted in cancer centers in Alabama, California, Georgia, Massachusetts and Texas.

Eligible patients must be able to perform all or most of their daily tasks independently (ECOG performance status of 2 or lower), and have one of the following CD19-positive B-cell malignancies:

• Diffuse large B-cell lymphoma (de novo or transformed)
• High-grade B-cell lymphoma
• Primary mediastinal large B-cell lymphoma
• Follicular lymphoma
• Mantle cell lymphoma
• Marginal zone lymphoma

The patient’s disease must be progressive and/or relapsed (came back after treatment) or refractory to (meaning that the treatment did not work or stopped working) two or more prior therapies.

Part A of the trial will be a dose escalation trial, meaning that researchers will test different amounts of the drug to determine the most effective and tolerable dose, as measured by safety and side effects. Then, part B is a dose-expansion, which will continue to test the optimal dose, which was determined in part A.

The researchers on the trial will also be analyzing preliminary overall response rate (percentage of patients whose disease disappears or shrinks from treatment); complete response rate (percentage of patients whose disease completely disappears); duration of response; and other laboratory and statistical outcomes.

CLN-978 is a type of treatment called a T-cell engager, which works by binding to the CD19, a target found on many B-cell malignancies such as B-NHL. The drug also to CD3 on T cells, thereby redirecting and activating T cells to find and destroy cancer cells.

According to the press release, CLN-978 is an off-the-shelf product, meaning that it is made from donor cells rather than patient cells — as is the case with CAR-T cell therapy — and the under-the-skin injection method allows for a “more patient-friendly dosing and potentially reduced toxicity,” the pharmaceutical company noted in the release.

“T-cell engagers have shown clinical activity in this patient population, and CD19 is a well-validated target for B-cell malignancies,” Jones said. “Based on preclinical evidence, we believe CLN-978 has a differentiated profile as it binds with very high affinity to CD19-expressing cells, even those with barely detectable levels of CD19. CLN-978 also offers patient-friendly administration and potentially reduced toxicity with an off-the-shelf treatment that is delivered subcutaneously. Collectively, these features may open up opportunities to investigate CLN-978 in additional CD19 mediated diseases.”

Researchers predict that the final data from the clinical trial will be completed by April 2027.

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