RB-1355 Is Safe and Well Tolerated in B- and T-Cell Lymphomas

RB-1355 monotherapy or in combination with radiotherapy demonstrated safety, tolerability, and preliminary efficacy among patients with B- and T-cell lymphomas, according to an oral presentation of the phase 1 first-in-human trial given at the 2026 Tandem Meetings.¹

Specifically, among 13 patients treated with RB-1355, only 3 treatment-related adverse effects (AEs) were observed in 2 patients, none of which were grade 3 or higher. The events included a cytomegalovirus reaction, injection site reaction, and cytokine release syndrome (CRS).

Additionally, no dose-limiting toxicities or any immune-related AEs after a median follow-up of 104 days were observed in the trial (range, 30-365). Moreover, the grade 1 CRS event was resolved with nonsteroidal anti-inflammatory drugs within 1 hour; however, it was reported twice in the same patient. This patient, treated at the dose level of 300 x 10⁶ cells, would later develop a durable complete response at 8 months of follow-up.

Regarding efficacy, 2 patients with diffuse large B-cell lymphoma (DLBCL) treated in the high-dose cohorts, one with and the other without external radiation therapy at 2.5 Gy, experienced a complete response among 12 evaluable patients. Moreover, a partial response was observed in 2 patients, both treated in the low-dose cohort with radiotherapy, and 3 patients experienced stable disease. An antilymphoma response was noted in 75% of patients.

“These early results are very encouraging and shine a light on how we can harness the power of the body’s immune system in a new way when treating patients,” Paolo Strati, MD, associate professor in the Department of Lymphoma/Myeloma in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center and presenting author of the trial, said in a news release on the study findings.² “This approach has the potential to open a new pathway for challenging lymphoma cases and patients who do not have effective treatments available to them.”

Patients in the phase 1 study were enrolled across 3 US centers and received 3 intravenous RB-1355 injections across 5 days, with a target enrollment of 12. No lymphodepletion was required prior to receipt of the investigational agent. Those eligible for enrollment had diagnosed B- or T-cell non-Hodgkin lymphoma relapsed or refractory to at least 2 prior lines of systemic therapy. Additionally, they were required to have at least 1 needle-accessible lesion between 1.5 and 5.0 cm in diameter and an ECOG performance status of 0 to 2.

The median age in the study was 63 years (range, 36-81), and 92% of patients were men. Most patients had an ECOG performance status of 0 (85%), had cutaneous T-cell lymphoma (38%) or DLBCL (23%), and had received 4 or more prior lines of therapy (62%).

The primary end point of the trial was to establish the safety and tolerability of RB-1355 and to determine the recommended phase 2 dose. Exploratory end points included preliminary antitumor activity, immune correlates, and repeat dosing regimens.

Additional findings revealed a strong correlation between response and fold change in intratumoral proliferating T cells (r = 0.8154; P = .019) as well as between response and posttreatment ratio of intratumoral M1(CXCL9):M2(SPP1) macrophages (r = 0.96; P = .0012).

Strati disclosed consulting relationships with AbbVie-Genmab, ADC Therapeutics, AstraZeneca-Acerta, BeOne, Incyte, Ipsen, Kite/Gilead, Lilly, Novartis, Roche-Genentech, and Sobi as well as having received research funds from ADC Therapeutics, ALX Oncology, AstraZeneca-Acerta, and Sobi.

References

1. Strati P, Feldman T, Kidder K, et al. Intratumoral cellular therapy with autologous M1 SIRPαlow macrophages in NHL: clinical results from a FIH phase 1 study. Abstract presented at: 2026 Transplantation & Cellular Therapy Meetings of American Society for Transplantation and Cellular Therapy and Center for International Blood and Marrow Transplant Research; February 4-7, 2026; Salt Lake City, UT. Abstract 76.
2. First-in-human study finds novel immune cell therapy is safe and effective in advanced lymphoma. News release. The University of Texas MD Anderson Cancer Center. February 7, 2026. Accessed February 9, 2026. https://tinyurl.com/2s3srtsy