G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology
company, today announced the presentation of mature Phase 2
clinical trial results describing the positive impact of
trilaciclib in combination with a TROP2 ADC (sacituzumab govitecan;
SG) on overall survival (OS) and tolerability compared to SG alone
based on historical data from the ASCENT trial1. The poster is
being presented during the Breast Cancer-Metastatic poster session
at the 2024 American Society of Clinical Oncology (ASCO) meeting,
held May 31 to June 4, 2024, and will be made available once the
poster is presented on June 2, 2024 on the G1 Therapeutics website
here.
The poster entitled, “Trilaciclib Combined with Sacituzumab
Govitecan (SG) in Metastatic Triple Negative Breast Cancer (mTNBC):
Updated Phase 2 Safety and Efficacy Results” (Seneviratne, L. et
al.) (abstract number 1091) describes the mature results from a
Phase 2 trial of trilaciclib in combination with SG in patients
with mTNBC. These results indicate that patients in the
intent-to-treat (ITT) population receiving trilaciclib with the ADC
experienced an approximately four-month improvement in median OS
(15.9 months vs 12.1 months) compared to that expected from the ADC
alone based on historical data from the ASCENT trial and had a
12-month survival of 60%. Further, in an exploratory analysis of a
potentially more comparable patient population to that enrolled in
the ASCENT trial, a 48% or approximately six-month improvement in
median OS (17.9 months vs 12.1 months) was observed in patients
receiving trilaciclib in combination with SG compared to historical
data from SG alone. Prolonged OS was observed in patients receiving
trilaciclib with the ADC who had an initial breast cancer diagnosis
of TNBC, prior use of checkpoint inhibitors, and no prior oral
CDK4/6 inhibitor use. The poster also describes the significant
on-target benefit of trilaciclib in reducing adverse events
associated with this ADC, including diarrhea, neutropenia, anemia,
and thrombocytopenia. These results support further evaluation of
trilaciclib prior to SG or other ADCs and will help determine the
design of future pivotal combination trials.
“While the development of therapies for the HER2+ and ER+
spectrum of disease is advancing quickly, TNBC remains an area
where we continuously seek to identify important therapeutic
signals with improved outcomes that should be further developed in
well-controlled pivotal clinical trials,” said Lasika Seneviratne,
M.D., Chief Medical Officer at Los Angeles Cancer Network and Chief
Scientific Officer of the Research Division of the Los Angeles
Cancer Network (LACN). “In this trial, trilaciclib significantly
reduced the side effect burden – neutropenia and diarrhea in
particular – associated with sacituzumab which can meaningfully
improve the tolerability of this important therapy. And although
cross-trial comparisons should be made with caution, we observed a
strong survival signal associated with use of trilaciclib prior to
sacituzumab in the ITT population in this trial compared to the
historical expectation of the ADC alone, and an even stronger
signal in the potentially more comparable data that censored
patients who received subsequent therapy with an ADC that was not
approved for patients with HER-2 low breast cancer at the time of
ASCENT. These are important and consistent hypothesis-generating
Phase 2 results that may, with further testing, provide an
opportunity to change the therapeutic landscape for patients living
with TNBC.”
The Phase 2 multicenter, open-label, single arm trial enrolled
30 patients with unresectable, locally advanced or metastatic TNBC
who received at least two prior treatments, at least one in the
metastatic setting. Trilaciclib was administered as a 30-minute IV
infusion completed within 4 hours prior to the start of SG
treatment on day 1 and day 8 of each 21-day cycle. The primary
endpoint was progression-free survival (PFS) per RECIST v1.1. Key
secondary endpoints included overall survival (OS),
myeloprotection, and safety/tolerability, as well as objective
response rate (ORR), clinical benefit rate (CBR; confirmed complete
response, partial response, or stable disease lasting ≥ 24 weeks
from first dose), and duration of response (DOR).
Patient Demographics
Enrolled patients (n=30) received a median of 6.0 cycles of
treatment, and median follow-up was 15.0 months. One patient
remains on study treatment and 12 patients remain in the study. The
median age of patients enrolled in the trial was 56.0 years. This
trial included a highly pretreated population of patients: 77% (23
of 30) received 2 or 3 prior systemic anticancer regimens, and 23%
(7 of 30) received greater than 3 prior systemic anticancer
regimens. A majority (73%; 22/30) of patients received prior
PD-(L)1 immunotherapy compared to 29% in the ASCENT trial and 20%
(6/30) of patients received prior oral CDK4/6 inhibitor treatment.
Sixty-seven percent (67%; 20/30) of patients had an initial
diagnosis of TNBC. Thirty percent (30%; 9/30) of patients received
subsequent anticancer therapy with fam-trastuzumab deruxtecan-nxki
(T-DXd).
Key Survival Analyses (n=30)
- In the overall ITT population,
patients receiving trilaciclib prior to SG experienced a median OS
of 15.9 months compared to the expected 12.1 months for SG alone
based on historical data from the ASCENT trial. Twelve-month OS was
60%.
- Since the conclusion of the ASCENT trial, the treatment
landscape has evolved and T-DXd has since been approved for use in
patients with HER2-low disease. Given that it was not an approved
indication for T-DXd at the time of ASCENT, an analysis was
conducted to exclude patients who received subsequent anticancer
therapy (SACT) with T-DXd by censoring patient data from the start
of SACT with T-DXd for those patients who received it. The outcomes
in this censored population are potentially more comparable to
results from the ASCENT study. In this patient population, median
OS among patients receiving trilaciclib was 17.9 months vs. 12.1
for SG alone.
Exploratory Survival Analyses
- All patients were diagnosed with
unresectable, locally advanced or metastatic TNBC at the time of
study entry. However, in patients who had an initial breast cancer
diagnosis of TNBC (n=20), median OS was 17.9 months compared to
12.0 months in those without TNBC as the initial diagnosis.
- In patients who had previously
received checkpoint inhibitor therapy with PD-(L)1 inhibitors
(n=22), median OS was 18.1 months compared to 11.4 months in
patients who did not receive checkpoint inhibitor therapy.
- In patients who did not receive prior oral CDK4/6i therapy
(n=24), median OS was 17.9 months compared to 8.0 months in those
who did.
In the overall population (N = 30), confirmed CBR was 47%
(14/30). ORR was 23% (7/30), with median DOR of 9.1 months. Median
PFS with trilaciclib administered prior to SG was 4.1 months,
unchanged from the initial efficacy analysis presented at the
European Society for Medical Oncology (ESMO) Breast Cancer 2023
meeting.
Safety Data (n=30)
Trilaciclib was well tolerated when administered prior to SG.
Mature safety results show a clinically meaningful on-target effect
of trilaciclib to reduce the rates of multiple treatment emergent
adverse events (TEAEs) associated with SG compared to the
previously published SG single agent safety profile from the ASCENT
trial, including measures of myelosuppression (neutropenia, anemia,
thrombocytopenia) and diarrhea due to the presence of
CDK4/6-expressing cells in the intestinal crypt.
Summary of TEAEs in patients receiving trilaciclib in
combination with SG |
|
|
|
Summary of TEAEs in patients receiving SG* |
Phase 2 trial of trilaciclib in combination with sacituzumab: TEAEs
(n=30) |
|
|
|
ASCENT (no trilaciclib): TEAEs (n=258) |
Adverse Event |
Any Grade |
Grade 3-4 |
|
|
|
Adverse Event |
Any Grade |
Grade 3-4 |
Diarrhea |
43% |
7% |
|
|
|
Diarrhea |
65% |
11% |
Neutropenia |
40% |
23% |
|
|
|
Neutropenia |
64% |
52% |
Anemia |
10% |
3% |
|
|
|
Anemia |
34% |
6% |
Thrombocytopenia |
0% |
0% |
|
|
|
Thrombocytopenia |
5% |
2% |
*Adapted from A Bardia, et al., Sacituzumab Govitecan in
Metastatic Triple-Negative Breast Cancer, N Engl J Med 2021;
384:1529-1541
“These mature Phase 2 results are compelling and will be
essential to determining the design of future pivotal combination
trials,” said Raj Malik, MD, G1 Therapeutics’ Chief Medical
Officer. “In particular, the approximately six-month improvement in
OS observed in the patient population that more closely mirrors
that of the ASCENT trial indicates an opportunity to meaningfully
enhance the therapeutic potential of a TROP2 ADC. We look forward
to sharing these data with the medical community at ASCO, and to
identifying the right partners to support advancement of this
important combination.”
About Triple Negative Breast Cancer
(TNBC)According to the American Cancer Society, nearly
300,000 new cases of invasive breast cancer are diagnosed annually
in the U.S. Triple-negative breast cancer makes up approximately
15-20% of such diagnosed breast cancers. TNBC is a cancer that
tests negative for estrogen receptors, progesterone receptors, and
excess HER2 protein. Because mTNBC cells lack key growth-signaling
receptors, patients do not respond well to medications that block
estrogen, progesterone, or HER2 receptors. Instead, treating mTNBC
typically involves chemotherapy, radiation, and surgery. TNBC is
considered to be more aggressive and have a poorer prognosis than
other types of breast cancer. In general, survival rates tend to be
lower with mTNBC compared to other forms of breast cancer, and
mTNBC is also more likely than some other types of breast cancer to
return after it has been treated, especially in the first few years
after treatment. It also tends to be higher grade than other types
of breast cancer.
About G1 TherapeuticsG1 Therapeutics, Inc. is a
commercial-stage oncology biopharmaceutical company whose mission
is to develop and deliver next-generation therapies that improve
the lives of those affected by cancer, including the Company’s
first commercial product, COSELA® (trilaciclib). The Company is
also evaluating therapies in combination with cytotoxic therapies
and/or immunotherapy in areas of high unmet need including
triple-negative breast cancer and extensive stage small cell lung
cancer. G1’s goal is to provide innovative therapeutic advances for
people living with cancer. G1 is based in Research Triangle Park,
N.C. For additional information, please visit
http://www.g1therapeutics.com and follow us on X (formerly known as
Twitter) @G1Therapeutics and LinkedIn.
G1 Therapeutics® and the G1 Therapeutics logo and COSELA® and
the COSELA logo are trademarks of G1 Therapeutics, Inc.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Words such as "may," "will," "expect," "plan," "anticipate,"
“could”, “believe,” “goal”, “projections,” "estimate," "intend,"
“indicate,” “potential,” “promising,” “opportunity,” “suggest,” and
similar expressions (as well as other words or expressions
referencing future events, conditions or circumstances) are
intended to identify forward-looking statements. Forward-looking
statements in this press release include, but are not limited to,
the ability of trilaciclib to significantly reduce the side effect
burden associated with this sacituzumab which can meaningfully
improve the tolerability of this ADC, and that these are
hypothesis-generating Phase 2 results that may, with further
testing, change the therapeutic landscape for these patients, are
based on the company’s expectations and assumptions as of the date
of this press release. Each of these forward-looking statements
involves risks and uncertainties. Factors that may cause the
company’s actual results to differ from those expressed or implied
in the forward-looking statements in this press release are
discussed in the company’s filings with the U.S. Securities
and Exchange Commission, including the "Risk Factors" sections
contained therein and include, but are not limited to, the
company’s dependence on the commercial success of COSELA
(trilaciclib); the development and commercialization of new drug
products is highly competitive; the company’s ability to complete
clinical trials for, obtain approvals for and commercialize any of
its product candidates; the company’s initial success in ongoing
clinical trials may not be indicative of results obtained when
these trials are completed or in later stage trials; the inherent
uncertainties associated with developing new products or
technologies and operating as a commercial-stage company; and
market conditions. Except as required by law, the company assumes
no obligation to update any forward-looking statements contained
herein to reflect any change in expectations, even as new
information becomes available.
G1 Therapeutics Contacts:
Will RobertsCommunications OfficerVice President, Investor
Relations and Corporate Communications(919) 907-1944
wroberts@g1therapeutics.com
_______________________
1 Bardia et al. Final Results from the Randomized Phase III
ASCENT Clinical Trial in Metastatic Triple-Negative Breast Cancer
and Association of Outcomes by Human Epidermal Growth Factor
Receptor 2 and Trophoblast Cell Surface Antigen 2
Expression." Journal of Clinical Oncology (2024):
JCO-23.
G1 Therapeutics (NASDAQ:GTHX)
Historical Stock Chart
From Jun 2024 to Jul 2024
G1 Therapeutics (NASDAQ:GTHX)
Historical Stock Chart
From Jul 2023 to Jul 2024