- Median Overall Survival was 15.7 months for all patients
treated with 100 mg quemliclustat-based regimens in the ARC-8
study, which exceeds the historical benchmark data for chemotherapy
alone
- A 37% reduction in risk of death and a 5.9-month improvement in
median overall survival was observed for patients treated with
quemliclustat-based regimens when compared to a Synthetic Control
Arm® (SCA®) of patients treated with chemotherapy alone in a
post-hoc analysis
- Detailed results will be presented at the ASCO Gastrointestinal
Cancers Symposium on January 19 from 12:30 – 2:00pm PT / 3:30 –
5:00pm ET
Arcus Biosciences, Inc. (NYSE:RCUS) today announced promising
overall survival data from ARC-8, a Phase 1b study that is being
co-developed with Gilead Sciences. ARC-8 is the study of
quemliclustat, an investigational small molecule CD73 inhibitor,
plus chemotherapy with or without zimberelimab, an investigational
anti-PD-1 antibody, in patients with previously untreated
metastatic pancreatic ductal adenocarcinoma (mPDAC). The results
will be presented during the 2024 American Society of Clinical
Oncology Gastrointestinal Cancers Symposium (ASCO GI).
“A quemliclustat-based regimen appears to meaningfully prolong
survival compared to what we typically observe in patients with
mPDAC who receive chemotherapy alone, the standard of care for more
than 30 years,” said Zev A. Wainberg, MD, MSc, Co-Director of the
GI Oncology Program at University of California Los Angeles and a
principal investigator of the ARC-8 trial. “CD73 is highly
expressed on pancreatic cancer cells, and I am encouraged to see
early evidence that inhibiting CD73 with a small molecule has the
potential to improve outcomes for people with mPDAC, without an
observed clinically meaningful increase in toxicity, when combined
with standard of care chemotherapy relative to historical data for
chemotherapy alone.”
The results to be presented include data from all patients
(n=122) with treatment-naïve (first-line) mPDAC who received 100mg
of quemliclustat plus chemotherapy with or without zimberelimab in
the dose-escalation, dose-expansion and randomization cohorts of
ARC-8. The data cutoff was June 19, 2023. Median overall survival
(mOS) data for both quemliclustat-based regimens were numerically
greater than historical benchmark data for chemotherapy alone,
which has shown a mOS of approximately nine months.
An analysis was performed by the Medidata AI team, part of
Medidata, a Dassault Systèmes company, whereby they constructed a
Synthetic Control Arm of patients who were treated with
gemcitabine/nab-paclitaxel in Phase 2 and 3 clinical studies in the
first-line metastatic pancreatic cancer setting, on a post-hoc
basis. Patients from these studies were matched 1:1 to the pool of
122 patients treated with the 100 mg quemliclustat-based regimens
in ARC-8, based on demographics and key baseline characteristics
such as ECOG performance status, liver metastasis, and history of
prior surgery. The matched SCA was constructed based on a
pre-specified analysis plan before OS data were unblinded and
analyzed by the Medidata AI team. The analysis showed that the
patients in ARC-8 lived longer than patients from the matched
control arm. Specifically, these results showed that patients in
ARC-8 experienced a:
- 37% reduction in the risk of death, HR=0.63 (CI: 0.47 – 0.85,
p=0.0030) and a
- 5.9-month increase in mOS (15.7 vs 9.8 months) relative to the
matched control arm.
The efficacy data for the pooled dose-escalation, dose-expansion
and randomized arms, as well as the data from the SCA, are
summarized below:
A2: Q+G/nP* (n=29)
A1: QZ+G/nP** (n=61)
Pooled Q100 QZ+G/nP***
(n=93)
All Pooled Q100 Q±Z+G/nP
(n=122)****
Post-hoc Synthetic Control Arm
(n=122)*****
Median OS, months (95% CI)
19.4 (12.1, 23.0)
14.6 (10.6, 21.5)
13.9 (11.1, 18.7)
15.7 (12.4, 20.9)
9.8 (7.8, 11.4)
Hazard Ratio
(95% CI)
HR=0.63 (0.47 – 0.85)
p=0.0030)
12-month OS
72.3%
60.9%
59.6%
62.7%
41.1%
Median PFS, months (95% CI)
8.8 (6.4, 12.6)
4.9 (3.7, 6.0)
5.4 (4.9, 7.3)
6.3 (5.4, 7.7)
5.5 (4.4, 6.6)
Hazard Ratio
(95% CI)
HR=0.78 (0.58‑1.05)
p=0.1102
ORR, % (95% CI)
41 (24, 61)
34 (23, 48)
38 (28, 48)
39 (29.9, 47.8)
41 (32.2, 50.3)
Q, Quemliclustat; Z, Zimberelimab; G/nP, gemcitabine /
nab‑paclitaxel; CI, confidence interval *Cohort A2 – patients
randomized to Q+G/nP in the dose-expansion phase. **Cohort A1 –
patients randomized to QZ+G/nP in the dose-expansion phase.
***Pooled Q100 QZ+G/nP – treatment-naïve patients receiving 100 mg
of quemliclustat plus zimberelimab and G/nP across dose-
escalation, expansion and randomization phases. ****All Pooled –
treatment-naïve patients receiving 100 mg of quemliclustat with or
without zimberelimab across dose- escalation, dose-expansion and
randomization phases. *****Synthetic Control Arm (Historical
Control) – Historical clinical trial data from patients treated
with G/nP, balanced to the baseline characteristics of ARC-8
participants. The Synthetic Control Arm data were compared to the
All Pooled group.
No new safety signals were observed in the study. The most
common adverse events (Grade 3 or higher) were neutropenia (37.9%,
34.4% and 38.7%) and anemia (27.6%, 26.2% and 23.7%), respectively,
for cohorts A2, A1 and Pooled Q100 QZ+G/nP. Five deaths were
reported, and none were considered by the study investigators to be
related to quemliclustat or zimberelimab.
Quemliclustat and zimberelimab are investigational molecules.
Arcus and Gilead have not received approval from any regulatory
authority for any use globally, and their safety and efficacy for
the treatment of pancreatic cancer have not been established.
About Quemliclustat
Quemliclustat is an investigational, potent and selective small
molecule CD73 inhibitor. CD73 is the primary enzymatic producer of
immunosuppressive adenosine in the tumor microenvironment, and high
CD73 expression is associated with significantly poorer prognosis
in several tumor types. Quemliclustat has been shown to block the
production of adenosine. Once the immunosuppressive effects of
adenosine are removed, activation of antitumor immune cells may be
restored, resulting in cancer cell death.
Arcus and Gilead are currently evaluating quemliclustat in
combination with other molecules within the collaboration portfolio
with chemotherapy, including Phase 2 studies in lung and upper
gastrointestinal cancers.
About the ARC-8 Trial
The ARC-8 trial is a Phase 1b, open-label, dose-escalation and
dose-expansion platform study to evaluate the safety, tolerability,
pharmacokinetic, pharmacodynamic and clinical activity of
combinations of the small molecule CD73 inhibitor quemliclustat,
anti-PD-1 antibody zimberelimab and chemotherapy (gemcitabine /
nab‑paclitaxel, or G/nP) in participants with advanced pancreatic
cancer.
After the dose-escalation phase, quemliclustat 100 mg was
selected as the dose for expansion. Patients were treated with
quemliclustat 100 mg every two weeks plus standard doses of
chemotherapy and zimberelimab (240 mg IV every two weeks) in Cohort
A (treatment-naïve mPDAC) of the dose-expansion phase and then
randomized 2:1 to receive quemliclustat plus zimberelimab and
chemotherapy (Cohort A1) or quemliclustat plus chemotherapy (Cohort
A2). Pooled analyses were conducted to reflect: 1) all
treatment-naïve patients who received quemliclustat 100 mg plus
zimberelimab and chemotherapy from dose-escalation and
dose-expansion phases and 2) all treatment-naïve patients receiving
100 mg of quemliclustat with or without zimberelimab across
dose-expansion and escalation phases. Endpoints included safety,
overall response rate, median overall survival and progression‑free
survival. More information about ARC-8 is available at:
https://www.clinicaltrials.gov/study/NCT04104672.
Additionally, an analysis comparing the All Pooled cohort to a
Synthetic Control Arm (SCA) was conducted to address the
differences in patient characteristics in the study cohorts,
particularly in relation to decreased presence of liver metastases
at baseline in cohort A2. The SCA consisted of historical clinical
trial data from patients treated with G/nP, with baseline
characteristics matched to those of ARC-8 participants.
About Pancreatic Cancer
Pancreatic cancer occurs in the pancreas, an organ located
behind the stomach that helps with digestion and controlling blood
sugar. Pancreatic cancer is one of the most aggressive cancers,
with a dismal prognosis. Approximately 50% of patients with PDAC
are diagnosed in the metastatic setting, which is associated with a
5-year survival rate of only 3%. Over 80% of pancreatic cancers are
diagnosed at a late stage. The majority (over 90%) of pancreatic
cancers are adenocarcinomas, a type of cancer that forms in tissues
that line certain internal organs and release fluids like those
that help with digestion. There have been limited advancements for
treating pancreatic cancer, and chemotherapy has been the standard
of care for more than 30 years.
About Arcus Biosciences
Arcus Biosciences is a clinical-stage, global biopharmaceutical
company developing differentiated molecules and combination
medicines for people with cancer. In partnership with industry
collaborators, patients and physicians around the world, Arcus is
expediting the development of first- and best-in-class medicines
against well-characterized biological targets and pathways and
studying novel, biology-driven combinations that have the potential
to help people with cancer live longer. Founded in 2015, the
company has expedited the development of multiple investigational
medicines into clinical studies, including new combination
approaches that target TIGIT, PD-1, the adenosine axis (CD73 and
dual A2a/A2b receptor), HIF-2a, CD39 and AXL. For more information
about Arcus Biosciences’ clinical and pre-clinical programs, please
visit www.arcusbio.com.
Forward-Looking Statements
This press release contains forward-looking statements. All
statements regarding events or results to occur in the future
contained herein are forward-looking statements reflecting the
current beliefs and expectations of management made pursuant to the
safe harbor provisions of the Private Securities Litigation Reform
Act of 1995, including, but not limited to, the statements in Dr.
Wainberg’s quote and statements regarding: the timing and scope of
analyses, data disclosures and presentations; whether data and
results from current studies support further development of a
program; and the potency, efficacy or safety of Arcus’s
investigational products. All forward-looking statements involve
known and unknown risks and uncertainties and other important
factors that may cause Arcus’s actual results, performance or
achievements to differ significantly from those expressed or
implied by the forward-looking statements. Factors that could cause
or contribute to such differences include, but are not limited to:
risks associated with preliminary and interim data not being
guarantees that future data will be similar; the unexpected
emergence of adverse events or other undesirable side effects;
difficulties or delays in initiating or conducting clinical trials
due to difficulties or delays in the regulatory process, enrolling
subjects or manufacturing or supplying product for such clinical
trials; Arcus’s dependence on the collaboration with Gilead for the
successful development and commercialization of its optioned
molecules; difficulties associated with the management of the
collaboration activities or expanded clinical programs; changes in
the competitive landscape for Arcus’s programs; and the inherent
uncertainty associated with pharmaceutical product development and
clinical trials. Risks and uncertainties facing Arcus are described
more fully in the “Risk Factors” section of Arcus’s most recent
Quarterly Report on Form 10-Q filed with the U.S. Securities and
Exchange Commission. You are cautioned not to place undue reliance
on the forward-looking statements, which speak only as of the date
of this press release. Arcus disclaims any obligation or
undertaking to update, supplement or revise any forward-looking
statements contained in this press release except to the extent
required by law.
The Arcus name and logo are trademarks of Arcus Biosciences,
Inc. All other trademarks belong to their respective owners.
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Investor Inquiries: Pia Eaves
Head of Investor Relations & Strategy (617) 459-2006
peaves@arcusbio.com
Media Inquiries: Holli Kolkey VP of Corporate
Communications (650) 922-1269 hkolkey@arcusbio.com
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