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 FIH trial given at the 2026 Tandem Meetings.¹

Specifically, among 13 patients treated with RB-1355, only 3 treatment-related adverse effects (TRAEs) were observed in 2 patients, none of which were grade 3 or higher. The events included a cytomegalovirus (CMV) 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 on trial (range, 30-365). Moreover, the grade 1 CRS event was resolved with nonsteroidal anti-inflammatory drugs and resolved was resolved within 1 hour, however it was reported twice in the same patient. This patient, treated at the 300 x 10⁶ cell dose level 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 (XRT) at 2.5 Gy, experienced a complete response (CR) among 12 evaluable patients. Moreover, a partial response (PR) was observed in 2 patients both treated in the low-dose cohort with radiotherapy, and 3 patients experienced stable disease. An anti-lymphoma 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, Division of Cancer Medicine at 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 (NHL) 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 to 5.0 cm in diameter and an ECOG performance status of 0 to 2.

The median age on the study was 63 years (range, 36-81), and 92% of patients were male. 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 post-treatment ratio of intratumoral M!(CXCL9) to-M2(SPP1) macrophages (r = .96; P = .0012).

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

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. Presented at: 2026 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; 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. MD Anderson Cancer Center. February 7, 2026. Accessed February 9, 2026. https://tinyurl.com/2s3srtsy