In a phase 1/2 dose escalation study, 29 previously untreated patients with low-grade B-cell lymphoma were treated with SD-101 (a CpG-oligonucleotide) and low-dose radiation at the same, single tumor site. 8 patients had grade 3 adverse events, primarily flu-like symptoms. Tumor burden was reduced in 26 patients (with 1 CR and 7 PR) and 24 patients had response in non-treated lesions. Responses were durable. The treatment increased IFNα response, CD8+, and CD4+ effector T cells, and decreased TFH and Tregs in the tumor. Low pretreatment levels of Tregs, Ki67+ CD8+ T cells, and granzyme B+ CD8+ T cells were associated with better clinical outcomes.
This multicenter phase 1/2 clinical trial evaluated intratumoral SD-101, a TLR9 agonist, and low-dose radiation in patients with untreated indolent lymphoma. 29 enrolled patients received 4 Gy of radiation followed by five weekly intratumoral injections of SD-101 at a single tumor site. No treatment-related grade 4 or serious adverse events occurred. Nearly all patients had tumor reduction at their treated site. More importantly, 24 patients had tumor reduction at their non-treated sites with 5 patients achieving a partial response and one achieving a complete response. Treatment-related increases of CD8+ and CD4+ effector T-cells and decreases of T Follicular Helper and T regulatory cells (Tregs) were observed in the tumor microenvironment. Low pre-treatment levels of CD4+ Tregs, proliferating CD8+ T-cells, and GranzymeB+ CD8+ T-cells were associated with favorable outcomes. Intratumoral SD-101 in combination with low-dose radiation is well tolerated and results in regression of both treated and untreated sites of disease.
Author Info: (1) Division of Oncology, Stanford University Hospital and Clinics. (2) University of Rochester Medical Center. (3) Siteman Cancer Center, Division of Hematology/Oncology, Washingt
Author Info: (1) Division of Oncology, Stanford University Hospital and Clinics. (2) University of Rochester Medical Center. (3) Siteman Cancer Center, Division of Hematology/Oncology, Washington University School of Medicine. (4) Hematology/Oncology, Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center. (5) University of Rochester Medical Center. (6) Division of Oncology, Stanford University Hospital and Clinics. (7) Division of Oncology, Stanford University Hospital and Clinics. (8) Division of Oncology, Stanford University Hospital and Clinics. (9) Dynavax Technologies Corporation. (10) Dynavax Technologies Corporation. (11) Dynavax Technologies Corporation. (12) Division of Oncology, Stanford University Hospital and Clinics levy@stanford.edu.
