- Promising anti-tumor activity in heavily
pretreated clear cell renal cell carcinoma (ccRCC) patients
- Objective response rate (ORR) of 21.4% and
disease control rate of 57%
- Biomarker data supports proof of mechanism
across multiple tumor types
- Combination therapy of SRK-181 and
pembrolizumab was generally well tolerated
- Company to discuss SRK-181 program during
conference call on third quarter 2023 financial results and
business updates, Tuesday, November 7th at 8 a.m. EST
Scholar Rock (NASDAQ: SRRK), a Phase 3, clinical-stage
biopharmaceutical company focused on the treatment of serious
diseases in which protein growth factors play a fundamental role,
today announced new data from its Phase 1 DRAGON proof-of-concept
trial of SRK-181, a selective inhibitor of latent TGFβ1 activation
being developed with the aim of overcoming resistance to checkpoint
inhibitor therapy in patients with advanced cancer. These data will
be presented in two poster presentations during the Society for
Immunotherapy of Cancer's (SITC) 38th Annual Meeting &
Pre-Conference being held November 1 – 5th in San Diego.
The first poster focuses on the safety, efficacy, and
preliminary biomarker data in patients with anti-PD-1 resistant
clear cell renal cell carcinoma (ccRCC) in Part A2 (dose
escalation) and Part B (dose expansion) of the Phase 1 DRAGON
trial. The ccRCC cohort was the focus for that poster, as it was
the fastest cohort to achieve enrollment goals. The second poster
focuses on preliminary biomarker data from part B of the trial in
patients with multiple tumor types.
Data presented continues to support proof of concept for SRK-181
in 28 heavily pretreated patients with ccRCC resistant to
anti-PD-1. SRK-181 was generally well tolerated and showed
promising anti-tumor activity in this patient population. Of 28
evaluable patients in the ccRCC cohort, six patients treated with
SRK-181 in combination with pembrolizumab had confirmed partial
responses (PRs) and achieved a best tumor reduction of 33% to 93%,
with an objective response rate (ORR) of 21.4%. In the biomarker
analysis for ccRCC, levels of circulating granulocytic
myeloid-derived suppressor cells (gMDSC) correlated with clinical
activity in ccRCC patients treated with SRK-181 in combination with
pembrolizumab. The data cutoff for all analyses was August 29,
2023.
“The DRAGON trial has successfully delivered on its objective of
demonstrating proof of concept for SRK-181 by showing promising
anti-tumor activity. These data, along with biomarker results that
support proof of mechanism, highlight the immunosuppressive role of
TGFβ as a mechanism of anti-PD-1 resistance in patients,” said Jay
Backstrom, M.D., M.P.H., President and Chief Executive Officer of
Scholar Rock. “We are particularly encouraged by the responses
observed in patients with ccRCC who had been treated with multiple
lines of therapy before receiving SRK-181.”
Safety data from ccRCC cohort continue to show SRK-181 is
generally well tolerated
Safety data from the ccRCC cohort (n=30 patients; part A2: 1
patient on 800mg q3w and 1 patient on 1600mg q3w and Part B: 28
patients on 1500 mg q3w) continue to show SRK-181 has been
generally well tolerated when used in combination with
pembrolizumab. No dose-limiting toxicities were observed at any
dose level, including at 1500 mg q3w in combination with
pembrolizumab, the recommended dose selected for Part B.
One Grade 4 treatment-related adverse event (AE) was observed,
dermatitis exfoliative generalized. No Grade 5 treatment-related
AEs occurred. Treatment-related serious adverse events were
dermatitis exfoliative generalized (1 patient), pemphigoid and rash
(both in 1 patient), immune-related hepatitis (1 patient), and
diarrhea, nausea, and vomiting (all three in 1 patient).
Preliminary results of SRK-181 in ccRCC patients show
promising anti-tumor activity
The response was assessed by principal investigators based on
RECIST 1.1. Out of the 28 ccRCC patients with evaluable responses
(defined as all enrolled patients except those who are still on
study, but pending post-treatment radiographic evaluation):
- Six patients had confirmed PRs (defined as at least a 30% tumor
reduction), with best tumor reduction of 33% to 93%, and remained
on study for 2.8+ to 16.3+ months (5 of the 6 patients remained on
for over 6.5 months).
- Ten patients had stable disease (SD) (defined as tumors with
neither sufficient shrinkage to qualify for PR nor sufficient
increase to qualify for progressive disease (PD). Five of these
patients continued in the study.
- The objective response rate (ORR), defined as the percentage of
patients with a partial or complete response to therapy, was 21.4%
and the disease control rate (DCR), defined as the percentage of
patients whose disease shrinks or remains stable over a certain
time period, was 57%. In this difficult to treat population,
anti-PD-1 retreatment is generally associated with single-digit ORR
or no response.1
Biomarker data support proof of mechanism in multiple tumor
types
The biomarker strategy includes measuring effects of SRK-181 on
both circulating and tumor immune cells, such as tumor infiltration
by CD8+ T cells and reductions in myeloid-derived suppressor cell
(MDSC) populations. The analysis included patients from Part B with
ccRCC, melanoma, non-small cell lung cancer (NSCLC), or urothelial
carcinoma (UC).
Following treatment with SRK-181 and pembrolizumab, circulating
MDSC levels decreased below baseline in all patients with PRs
(n=7), which included those in the ccRCC, melanoma, and UC cohorts.
CD8+ T cells were measured in tumor types for which paired biopsy
samples (i.e., samples before and after treatment for individual
patients) of sufficient quality were available: UC, melanoma, and
NSCLC. In those patients (n=8), SRK-181 treatment was associated
with an increase in CD8+ T cell infiltration into tumors. These
findings were consistent with preclinical data showing that
treatment with SRK-181 and anti-PD-(L)1 therapy decreased
circulating MDSC levels and increased CD8+ T cell infiltration into
tumors, which correlated with tumor response and survival
benefit.
The results will be presented at the SITC 38th Annual Meeting in
two poster presentations, details of which can be found below. The
posters will be made available in the Publications & Posters
section of Scholar Rock’s website following the conference.
Title: Establishing Proof of Mechanism in Patients:
Preliminary Biomarker Data of SRK-181 (a latent TGFβ1 inhibitor)
from DRAGON Study Presentation Type: Poster 726
Presenter: Susan Henry, PhD, Senior Director, Translational
Sciences, Scholar Rock, Inc. Location: Exhibit Halls A and
B1, San Diego Convention Center Date/Time: November 4, 11:55
AM – 1:25 PM PST and 7 – 8:30 PM PST
Title: Safety, Efficacy, and Biomarker Results of
SRK-181, a Latent TGFβ1 Inhibitor, in Anti-PD-1 Resistant
Metastatic ccRCC Patients Presentation Type: Poster 666
Presenter: Timothy Yap, MBBS, PhD, FRCP, Medical Oncologist
and Physician-Scientist; and Associate Professor, Department of
Investigational Cancer Therapeutics, University of Texas MD
Anderson Cancer Center Location: Exhibit Halls A and B1, San
Diego Convention Center Date/Time: November 4, 11:55 AM –
1:25 PM PST and 7 – 8:30 PM PST
For conference information, visit
https://www.sitcancer.org/2023/home
(1) Pal, et al. The Lancet. 2023; 15;402(10397):185-195.
About SRK-181
SRK-181 is a selective inhibitor of TGFβ1 activation being
developed to overcome primary resistance to checkpoint inhibitor
therapy, such as anti-PD-(L)1 antibodies, in advanced cancer. TGFβ1
is the predominant TGFβ isoform expressed in many human tumor
types. Based on analyses of various human tumors that are resistant
to anti-PD-(L)1 therapy, data suggest that TGFβ1 is a key
contributor to the immunosuppressive tumor microenvironment,
excluding and preventing entry of cytotoxic T cells into the tumor,
thereby inhibiting anti-tumor immunity. (2) SRK-181 specifically
targets the latent TGFβ1 isoform in a context-independent manner,
designed to enable complete inhibition of TGFβ1 in all compartments
within the tumor microenvironment. Scholar Rock believes that
SRK-181 has the potential to overcome this immune cell exclusion
and induce tumor regression when administered in combination with
anti-PD-(L)1 therapy while potentially avoiding toxicities
associated with non-selective TGFβ inhibition. The DRAGON Phase 1
proof-of-concept clinical trial (NCT04291079) in patients with
locally advanced or metastatic solid tumors is ongoing. The trial
is currently enrolling and dosing patients in multiple proof of
concept cohorts conducted in parallel, including urothelial
carcinoma (UC), cutaneous melanoma (MEL), non-small cell lung
cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and
clear cell renal cell carcinoma (ccRCC). SRK-181 is an
investigational product candidate and its efficacy and safety have
not been established. SRK-181 has not been approved for any use by
the FDA or any other regulatory agency.
2) Martin et al., Sci. Transl. Med. 12: 25
March 2020
About Scholar Rock
Scholar Rock is a biopharmaceutical company that discovers,
develops, and delivers life-changing therapies for people with
serious diseases that have high unmet need. As a global leader in
the biology of the transforming growth factor beta (TGFβ)
superfamily of cell proteins and named for the visual resemblance
of a scholar rock to protein structures, the clinical-stage company
is focused on advancing innovative treatments where protein growth
factors are fundamental. Over the past decade, the company has
created a pipeline with the potential to advance the standard of
care for neuromuscular disease, cardiometabolic disorders, cancer,
and other conditions where growth factor-targeted drugs can play a
transformational role.
Scholar Rock is the only company to show clinical proof of
concept for a muscle-targeted treatment in spinal muscular atrophy
(SMA). This commitment to unlocking fundamentally different
therapeutic approaches is powered by broad application of a
proprietary platform, which has developed novel monoclonal
antibodies to modulate protein growth factors with extraordinary
selectivity. By harnessing cutting-edge science in disease spaces
that are historically under-addressed through traditional
therapies, Scholar Rock works every day to create new possibilities
for patients. Learn more about the company’s approach at
ScholarRock.com and follow @ScholarRock and on LinkedIn.
Availability of Other Information About Scholar Rock
Investors and others should note that we communicate with our
investors and the public using our company website
www.scholarrock.com, including, but not limited to, company
disclosures, investor presentations and FAQs, Securities and
Exchange Commission filings, press releases, public conference call
transcripts and webcast transcripts, as well as on Twitter and
LinkedIn. The information that we post on our website or on Twitter
or LinkedIn could be deemed to be material information. As a
result, we encourage investors, the media and others interested to
review the information that we post there on a regular basis. The
contents of our website or social media shall not be deemed
incorporated by reference in any filing under the Securities Act of
1933, as amended.
Scholar Rock® is a registered trademark of Scholar Rock,
Inc.
Forward-Looking Statements
This press release contains "forward-looking statements" within
the meaning of the Private Securities Litigation Reform Act of
1995, including, but not limited to, statements regarding Scholar
Rock’s future expectations, plans and prospects, including without
limitation, Scholar Rock’s expectations regarding its growth,
strategy, and progress and indication selection and development
timing, the ability of any product candidate to perform in humans
in a manner consistent with earlier nonclinical, preclinical or
clinical trial data, and the potential of its product candidates
and proprietary platform. The use of words such as “may,” “might,”
“could,” “will,” “should,” “expect,” “plan,” “anticipate,”
“believe,” “estimate,” “project,” “intend,” “future,” “potential,”
or “continue,” and other similar expressions are intended to
identify such forward-looking statements. All such forward-looking
statements are based on management's current expectations of future
events and are subject to a number of risks and uncertainties that
could cause actual results to differ materially and adversely from
those set forth in or implied by such forward-looking statements.
These risks and uncertainties include, without limitation, that
clinical data, including the results from the Phase 2 clinical
trial of apitegromab, or Part B of the Phase 1 clinical trial of
SRK-181, and are not predictive of, may be inconsistent with, or
more favorable than, data generated from future clinical trials of
the same product candidates, Scholar Rock’s ability to provide the
financial support, resources and expertise necessary to identify
and develop product candidates on the expected timeline, the data
generated from Scholar Rock’s nonclinical and preclinical studies
and clinical trials, and Scholar Rock’s ability to manage expenses
and to obtain additional funding when needed to support its
business activities, as well as those risks more fully discussed in
the section entitled "Risk Factors" in Scholar Rock’s Quarterly
Report on Form 10-Q for the quarter ended June 30, 2023, as well as
discussions of potential risks, uncertainties, and other important
factors in Scholar Rock’s subsequent filings with the Securities
and Exchange Commission. Any forward-looking statements represent
Scholar Rock’s views only as of today and should not be relied upon
as representing its views as of any subsequent date. All
information in this press release is as of the date of the release,
and Scholar Rock undertakes no duty to update this information
unless required by law.
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Scholar Rock:
Investors Rushmie Nofsinger Scholar Rock
rnofsinger@scholarrock.com ir@scholarrock.com 857-259-5573
Media Molly MacLeod Scholar Rock mmacleod@scholarrock.com
media@scholarrock.com 802-579-5995
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