Overall Response Rate of 76% in Advanced Melanoma Patients with Dynavax’s SD-101 in Combination with KEYTRUDA® (pembrolizu...
June 03 2019 - 2:15PM
Dynavax Technologies Corporation (NASDAQ: DVAX), today announced
increasingly favorable results from the Phase 1b/2 (SYNERGY-001),
open-label, multicenter study of the combination of SD-101 and
KEYTRUDA® (pembrolizumab) in advanced melanoma patients who are
naïve to anti-PD-1/PD-L1 treatment. The results were presented
today in a poster session at the 2019 American Society of Clinical
Oncology (ASCO) Annual Meeting.
“To consistently see an overall response rate above 70% among
advanced melanoma patients, which has historically been a difficult
population to treat, is very encouraging and exciting,” said Robert
Janssen, M.D., chief medical officer of Dynavax. “Additionally, in
response to treatment, we have seen immunologically cold tumors
reach similarly high levels of immune cell activation as
immunologically hot tumors.”
The Phase 1b/2 clinical study (NCT02521870) in patients with
advanced melanoma is ongoing. In the study, SD-101 is administered
intratumorally with 8 mg in 1 lesion or 2 mg in 1–4 lesions
combined with intravenous administration of 200 mg of
pembrolizumab.
Key highlights from the clinical data presentation include:
- Efficacy: º The overall response rate (ORR) in the SD-101
2 mg/lesion group (76%) was higher than in the SD-101 8 mg/lesion
group (49%)º The median duration of response (DOR) in both groups
has not been reached, with the lower bound of the 95% confidence
interval of at least 14 monthsº The 18-month progression free
survival (PFS) rate in the SD-101 2 mg/lesion group (72%) was
higher than in the SD-101 8 mg/lesion group (36%)º Similar rates of
responses occurred in patients with PD-L1 negative tumors and PD-L1
positive tumorsº Tumor shrinkage has been observed in both injected
and non-injected lesions, including visceral lesions such as the
liver and lung
- Immunologically cold tumors are a therapeutic challenge for
anti-PD-1 therapy; the ability of SD-101 with pembrolizumab to
convert cold tumors (PD-L1 negative, low IFNγ and T cell signature
at baseline) into T cell rich tumors is demonstrated by biomarker
data in the samples tested º This ability to convert cold into
inflamed tumors is consistent with similar effects in head and neck
squamous cell carcinoma (HNSCC) (ASCO 2019, Abstract
6039)
- The superior induction of infiltrating effector immune cells in
lesions treated with the 2 mg/lesion dose compared with 8 mg/lesion
is consistent with the increased response observed
- The combination of SD-101 and pembrolizumab was well tolerated,
consistent with previous report º AEs associated with SD-101 were
transient, mild to moderate injection-site reactions and flu-like
symptoms that were manageable with over-the-counter medicationsº No
increase in immune-related AEs over pembrolizumab monotherapy were
observed
A table accompanying this announcement is available at
https://www.globenewswire.com/NewsRoom/AttachmentNg/d03e76d2-86e7-4675-ae1d-8a29251f5101
- The ORR in patients with BRAF mutant tumors who received 2
mg/lesion (n=18) was 61%
- The ORR in patients with PD-L1 negative tumors who received 2
mg/lesion (n=14) was 79%
In addition, the company presented data from the Phase 1b/2,
open label, multicenter, study of the combination of SD-101 and
pembrolizumab in patients with advanced/metastatic melanoma
resistant to anti-PD-1/PD-L1 therapy.
Key highlights from the clinical data presentation include:
- Efficacy results from the combination of SD-101 and
pembrolizumab in confirmed PD-1 resistant or refractory patients
demonstrated an 19.4% ORR in the SD-101 2 mg/lesion group and a
13.3% ORR in the SD-101 8 mg/lesion group
- Responses were observed in SD-101 injected and non-injected
lesions (including liver and lung metastases)
- Responses and disease control were observed in BRAF mutant or
wild type tumors
- Biomarker data demonstrate that SD-101 added to pembrolizumab
significantly changes the tumor microenvironment of patients that
previously failed PD-1 blockade including the infiltration of
activated T cells, NK cells, and B cells
- The combination of SD-101 and pembrolizumab was well tolerated,
consistent with previous reports º No evidence of an increased
incidence or severity of AEs over pembrolizumab monotherapyº No
increase in immune-related AEs over pembrolizumab monotherapyº AEs
associated with SD-101 were mainly mild to moderate injection-site
reactions and flu-like symptoms that were manageable with
over-the-counter medications
In addition, a poster titled: “Overcoming genetically based
resistance mechanisms to PD-1 blockade” (Abstract No: 2584) was
presented. The goal of the preclinical study was to assess
mechanism-based strategies to overcome resistance to anti-PD1
therapy. Results demonstrated that even in the extreme setting of
genetic resistance to PD-1 blockade by JAK1/2 LoF, resistance can
be overcome by SD-101, a TLR9 agonist.
About SYNERGY-001 (KEYNOTE-184)SYNERGY-001,
previously referred to as MEL-01, is a Phase 1b/2
SYNERGY-001/KEYNOTE-184 trial in combination with KEYTRUDA which
includes patients with histologically or cytologically confirmed
unresectable Stage IIIC/IV melanoma. The primary endpoint of the
trial is objective response rate assessed by RECIST v1.1. The
secondary endpoints are safety and tolerability, progression-free
survival and duration of response, with an exploratory endpoint of
immunophenotype of the tumor microenvironment.
About SD-101SD-101 is a proprietary,
second-generation, Toll-like receptor 9 (TLR9) agonist CpG-C class
oligodeoxynucleotide. Dynavax is evaluating SD-101 in several
clinical studies to assess its safety and activity, including a
Phase 2 study in combination with KEYTRUDA® (pembrolizumab) in
advanced melanoma and metastatic or recurrent head and neck
squamous cell cancer in collaboration with Merck, and in high risk
breast cancer in collaboration with I-SPY 2. Dynavax maintains all
commercial rights to SD-101.
About DynavaxDynavax is a fully-integrated
biopharmaceutical company focused on leveraging the power of the
body's innate and adaptive immune responses through toll-like
receptor (TLR) stimulation. Dynavax discovers and develops novel
vaccines and immuno-oncology therapeutics. The Company is currently
exploring strategic alternatives for its immuno-oncology portfolio.
The Company launched its first commercial product, HEPLISAV-B®
[Hepatitis B Vaccine (Recombinant), Adjuvanted], in February 2018,
following U.S. FDA approval for prevention of infection caused by
all known subtypes of hepatitis B virus in adults age 18 years and
older. For more information, visit www.dynavax.com.
Forward-Looking Statements (update)This press
release contains "forward-looking" statements, including statements
regarding the conduct of clinical trials of SD-101, including
results from the Phase 1b/2 trial, and potential value of SD-101
across multiple tumor types. Actual results may differ materially
from those set forth in this press release due to the risks and
uncertainties inherent in our business, including whether we can
timely provide adequate clinical supplies; initiation, enrollment
and completion of clinical trials of SD-101; whether interim and
final results of current and future clinical trials will support
the initiation or continuation of subsequent trials by us or
another party; issues arising in the regulatory process; the
ability to successfully develop or pursue strategic alternatives
for SD-101, including the funding of future studies as
well as other risks detailed in the "Risk Factors" section of our
Annual Report on Form 10-K for the fiscal year ended December 31,
2018 and in our Quarterly Report on Form 10-Q for the quarter ended
March 31, 2019, as well as discussions of potential risks,
uncertainties and other important factors in our other filings with
the U.S. Securities and Exchange Commission. We undertake no
obligation to revise or update information herein to reflect events
or circumstances in the future, even if new information becomes
available. Information on Dynavax's website at www.dynavax.com is
not incorporated by reference in our current periodic reports with
the SEC.
Contact:
Heather Rowe
Vice President, Investor Relations & Corporate Communications
hrowe@dynavax.com
510-665-7269
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