Download bstract of the study was presented at the American

2974
SD-101, a Novel Class C CpG-Oligodeoxynucleotide (ODN)
Toll-like Receptor 9 (TLR9) Agonist, Given with Low Dose
Radiation for Untreated Low Grade B-Cell Lymphoma: Interim
Results of a Phase 1/2 Trial
Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies
Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Poster II
Sunday, December 4, 2016, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)
Ronald Levy, MD1, Patrick Reagan, MD2, Jonathan W. Friedberg, MD3, Nancy L Bartlett, MD4, Leo I.
Gordon, MD5, Abraham Leung, MD6*, Joanna Peterkin, MD, MS6*, Biao Xing6*, Robert Coffman, PhD7,
Robert Janssen, MD7*, Albert Candia, PhD6*, Michael Khodadoust, MD, PhD8, Matthew J. Frank, MD,
PhD8, Steven R Long, MD9*, Debra K Czerwinski8 and Michael Chu, MD10*
Stanford University, Stanford, CA
1
Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY
2
Wilmot Cancer Institute, University of Rochester, Rochester, NY
3
Siteman Cancer Center, Washington University School of Medicine, Saint Louis, MO
4
Department of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg
5
School of Medicine, Chicago, IL
Dynavax, Berkeley, CA
6
Dynavax Technologies, Berkeley, CA
7
Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA
8
Pathology, Stanford University School of Medicine, Stanford, CA
9
Stanford University School of Medicine, Stanford, CA
10
Introduction: Prior studies have shown preliminary clinical efficacy in combining CpG-ODN with
radiation therapy (XRT) to patients with indolent B-cell lymphoma. We report interim Phase 1/2 data
of combination XRT and SD-101, a synthetic class C CpG-ODN TLR9 agonist, selected for the strong
induction of type I interferon.
Methods: This dose-escalation Phase 1/2 trial enrolled patients with untreated indolent B-cell
lymphoma having at least 2 measurable lesions (one palpable). The primary endpoints were safety
and alpha-interferon-gene induction. Secondary endpoints included efficacy assessment using
Cheson (1999) criteria and quantification of changes in tumor-infiltrating lymphocytes. A single
lesion was treated with XRT (2 Gy daily X 2 days) followed by a single intratumoral dose of SD-101
(same lesion). 4 additional doses of intratumoral SD-101 were given weekly over next 4 weeks. The
treated lesion and distal lesions were monitored during the study. Pharmacodynamic assessment
included flow cytometry analysis of immune infiltrates in an FNA sample of the treated tumor and
RT-PCR RNA assay of whole blood to assess induction of alpha-interferon genes. Efficacy
assessment included imaging (CT at 3, 6, and every 6 months thereafter).
Results: As of 01 Aug 2016, 13 patients were treated with escalating doses of SD-101 at 1, 2, 4 or 8
mg/dose. There were no dose limiting toxicities. The majority of related adverse events (AEs) were
Grade 1 (mild). The most common were flu-like symptoms (chills, headache, malaise, myalgia),
typically resolving within ≤ 48 hours without requiring intervention (e.g., acetaminophen). An
induction of alpha-interferon genes occurred at all dose levels with a similar level of induction.
For the dose expansion phase, 15 patients were enrolled at 1 mg (6) and 8 mg dose group (9).
Similar to dose escalation phase, the most common related events were again flu-like symptoms,
typically resolving within ≤ 48 hours mitigated with acetaminophen. There was one dose delay for
Grade 3 neutropenia in one patient (1 mg) that resolved following drug interruption. Twenty-nine
Grade 3 transient flu-like symptoms were reported for four patients (44%) who received the 8 mg
dose (e.g., chills headache, malaise, myalgia, and fatigue). Only one of the four patients experienced
all 5 Grade 3 flu-like symptoms after intratumoral injection. There were no grade 4 or serious events
reported, and no patient discontinued due to an adverse event.
A reduction in tumor sizes was observed in the study over time (see Figure 1). At Day 90 the median
changes in the product of diameters from baseline were -46.1% and -10.2% for treated tumor and
distal tumors, respectively. At Day 540, the median changes were -68.6% and -24.1%, respectively.
In patients with follicular lymphoma (largest subgroup), preliminary data suggest a higher
percentage of CD8+ T cells in the treated lesion (FNA at day 8) correlated with an increased abscopal
response.
Conclusions: Intratumoral SD-101 following radiation therapy has been well tolerated and
preliminary efficacy, promising. Abscopal anti-tumor activity was observed with preliminary data
suggesting that a higher percentage of CD8+ T cells in the treated lesion correlated with an
increased abscopal response seen in follicular lymphoma. Enrollment is ongoing with an option for
cycle 2 retreatment.
Disclosures: Levy: Dynavax: Research Funding; Corvus: Consultancy; Beigene: Consultancy; Innate
Pharma: Consultancy; Five Prime Therapeutics: Consultancy; Kite
Pharma: Consultancy; Pharmacyclics: Research Funding. Reagan: Seattle Genetics: Research
Funding. Friedberg: Bayer: Other: Data Safety Monitoring
Committee. Bartlett:Gilead: Consultancy. Leung: Dynavax: Employment. Peterkin: Dynavax: Consultan
cy. Xing: Dynavax: Employment. Coffman: Dynavax: Employment. Janssen: Dynavax: Employment. Ca
ndia: Dynavax: Employment.