SynKIR-310 Dosing for B-NHL Begins in CELESTIAL-301 Trial

This article was first published by Targeted Oncology™. This version has been lightly edited.

The first patient with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL) has been dosed with SynKIR-310 in the CELESTIAL-301 trial (NCT06544265).¹ The patient was treated at Sarah Cannon Research Institute at Colorado Blood Cancer Institute (CBCI) in Denver, Colorado.

CELESTIAL-301 is a phase 1, multicenter study evaluating the safety, tolerability, and preliminary efficacy of SynKIR-310 in patients relapsed/refractory B-NHL, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma.

Laura Johnson, PhD | Image Credit: © Verismo Therapeutics/LinkedIn

"The initiation of patient dosing in the CELESTIAL-301 trial marks an exciting milestone for Verismo Therapeutics as we advance our mission to develop transformative therapies for patients facing advanced lymphomas. CBCI's commitment to patients and to conducting novel early-stage clinical trials has allowed us to reach this milestone earlier than expected," said Laura Johnson, PhD, chief operations officer and chief scientific officer at Verismo Therapeutics, in a statement. "SynKIR-310 is uniquely designed to prolong T-cell functional persistence and combat the challenges of disease relapse, offering a potentially life-saving option for these patients."

SynKIR-310 is a chimeric antigen receptor (CAR) T-cell therapy that relies on DS191. Like commercially approved CAR T-cell therapies, SynKIR-310 is directed by DS191 to target a similar epitope of CD19. SynKIR-310, however, has added potential to prolong antitumor T-cell function and persistence.

In May 2024, the FDA granted clearance to an investigational new drug application for SynKIR-310, allowing for the start of the CELESTIAL-301 study in patients with relapsed/refractory B-NHL, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma.²

CELESTIAL-301 is the company's second study investigating the KIR-CAR platform technology.

Enrollment in the phase 1 trials is open to patients with R/R B-NHL who previously were treated with CAR T-cell therapy but who have since relapsed or become refractory to it.³ Patients who never received CAR T-cell therapy are also eligible for enrollment.

Patients must be 18 years or older with a histologically confirmed diagnosis of B-NHL prior to enrollment. Additional inclusion criteria for the trial are that patients have refractory or relapsed disease after receiving 2 prior lines of therapy, measurable disease at the time of enrollment, and an Eastern Cooperative Oncology Group performance status of 0 or 1.

Regardless of subtypes of B-NHL, up to 18 patients who meet the eligibility criteria will be enrolled and treated in the study. There will be 2 cohorts included in the trial, consisting of 3 to 6 patients per cohort. Doses will be escalated across 2 cohorts to determine a recommended phase 2 dose (RP2D).

The primary end points of the study are to assess the incidence, frequency, and severity of adverse events (AEs), including serious AEs, treatment-emergent AEs, and dose-limiting toxicities, and to determine the RP2D of the agent. Secondary end points will evaluate the feasibility of SynKIR-310, objective response rate, complete response rate, duration of response, pharmacodynamics, and pharmacokinetics.

Once the RP2D has been determined, a dose expansion group will enroll additional patients, regardless of subtypes of B-NHL, aiming to further characterize the safety, feasibility, and preliminary efficacy of SynKIR-310 in this patient population.

References

1. Verismo Therapeutics announces first patient infused in phase 1 CELESTIAL-301 clinical trial of SynKIR-310. News release. Verismo Therapeutics. January 10, 2025. Accessed January 20, 2025. https://www.prnewswire.com/news-releases/verismo-therapeutics-announces-first-patient-infused-in-phase-1-celestial-301-clinical-trial-of-synkir-310-302347464.html

2. Verismo Therapeutics receives IND clearance from the FDA for SynKIR-310 in relapsed/refractory B-cell NHL. News release. Verismo Therapeutics. May 14, 2024. Accessed January 20, 2025. https://www.prnewswire.com/news-releases/verismo-therapeutics-receives-ind-clearance-from-the-fda-for-synkir-310-in-relapsedrefractory-b-cell-nhl-302144410.html

3. SynKIR-310 for relapsed/refractory B-NHL. ClinicalTrials.gov. Updated November 22, 2024. Accessed January 20, 2025. https://clinicaltrials.gov/study/NCT06544265