G1 Therapeutics Presents New Post Hoc Analyses Indicating That Patients Who Previously Received Trilaciclib Have Improved Overall Survival with Subsequent Anticancer Therapy
05 Diciembre 2023 - 8:26AM
G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology
company, today announced the presentation of new data describing
the long-term positive survival impact of previous treatment with
trilaciclib and cytotoxic chemotherapy (gemcitabine/carboplatin;
GCb) in patients with metastatic triple negative breast cancer
(mTNBC) who participated in G1’s Phase 2 trial (NCT02978716). The
poster is being presented at the 2023 San Antonio Breast Cancer
Symposium (SABCS), held December 5th to 9th in San Antonio, TX, and
is available on the G1 Therapeutics website here.
The poster entitled, “Patients with Metastatic Triple-Negative
Breast Cancer Who Receive Trilaciclib Prior to Cytotoxic
Chemotherapy Exhibit Improved Survival After Receiving Subsequent
Anticancer Therapy” describes a post hoc analysis of data from G1
Therapeutics’ randomized Phase 2 mTNBC trial (NCT02978716;
completed February 2020) indicating that patients with mTNBC who
received trilaciclib with their cytotoxic chemotherapy during the
trial and then received subsequent anticancer therapy (SACT) after
trilaciclib discontinuation exhibit statistically significant and
clinically meaningful improvements in median overall survival (OS)
(32.7 months versus 12.8 months; p=0.001) and in median OS from
start of first SACT (14.0 months versus 5.8 months; p=0.001)
compared to those who received cytotoxic chemotherapy without
trilaciclib and then received SACT. Administering trilaciclib with
cytotoxic chemotherapy also led to improved survival in patients
unable to receive SACT.
“These new analyses indicate that trilaciclib can protect the
bone marrow and immune system against the harmful effects of
cytotoxic therapy, leading to significantly improved survival
outcomes among patients who receive subsequent anticancer
therapies,” said Raj Malik, M.D., Chief Medical Officer at G1
Therapeutics. “The findings are particularly relevant as we are
evaluating the impact of trilaciclib on long-term endpoints
including overall survival in PRESERVE 2, our ongoing pivotal Phase
3 mTNBC trial, with the interim overall survival analysis expected
in the first quarter of 2024.”
The Phase 2 trial (NCT02978716) enrolled patients who had
received up to two prior chemotherapy regimens for locally
recurrent or mTNBC. Participants were randomized into three groups:
GCb alone on days 1 and 8 (n=34), trilaciclib prior to GCb on days
1 and 8 (n=33), or trilaciclib alone on days 1 and 8 and prior to
GCb on days 2 and 9 (n=35). G1 conducted a post hoc survival
analysis on data from patients in this Phase 2 TNBC trial who
received additional anticancer therapies after discontinuation of
study treatment with GCb with or without trilaciclib, to evaluate
improvements in long-term outcomes; the two trilaciclib groups were
combined for this analysis. The SACTs administered include
gemcitabine, capecitabine, eribulin, taxane, carboplatin, and
PD-1/PD-L1 inhibitors. Additionally, murine cancer models were
utilized to quantify the infiltration of central memory T cells in
the tumor microenvironment seven days after a single dose or seven
daily doses of trilaciclib. Memory T cell recall responses (the
ability of memory T cells to react rapidly on encounter with the
same antigen after remission) were also evaluated.
Survival Outcomes
- After a median follow-up of 12.7
months on study, deaths were observed in 22/43 patients in the
trilaciclib plus GCb group and 17/20 patients in the GCb-only group
(no trilaciclib). Median time on treatment was 5.5 months in the
trilaciclib plus GCb group and 3.3 months in the GCb-only
group.
- Patients receiving SACT following
trilaciclib plus GCb exhibited statistically significant (p=0.001)
improvements in median (95% CI) OS (32.7 months; 15.3 – not
estimable) compared to those receiving SACT following GCb alone
(12.8 months; 8.3 – 17.8), with increasing separation of survival
curves over time.
- Median OS and progression-free
survival (PFS) were higher in the prior trilaciclib plus GCb group
compared with the prior GCb-only group, regardless of the type of
SACT received.
- Improved survival and sustained
separation of curves were also observed in patients unable to
receive SACT (trilaciclib, n = 25; placebo, n = 14), although the
magnitude of benefit was smaller (median 9.4 vs 5.4 months).
- Patients receiving SACT following
trilaciclib plus GCb also exhibited statistically significant
(p=0.001) improvements in median (95% CI) OS from start of the
first SACT (14.0 months; 9.0 – not estimable) compared to those
receiving SACT following GCb alone (5.8 months; 4.8 – 7.2).
Immune Surveillance Results
In addition, data from murine models indicate that
trilaciclib-mediated transient cyclin-dependent kinase (CDK)4/6
inhibition may enhance tumor infiltration of CD8+ central memory T
cells and boost memory T cell recall responses, further clarifying
the mechanism by which trilaciclib improves long-term immune
surveillance:
- Compared with daily dosing, a single
dose of trilaciclib resulted in an increase in the number of tumor
infiltrating CD8+ central memory T cells in the tumor
microenvironment on day seven.
- Administering trilaciclib enhanced
the efficacy of combination immunotherapy with α-PD-1 plus α-LAG3;
seven of eight mice that received trilaciclib plus α-PD-1 and
α-LAG3 survived (achieved a complete response) compared to three of
eight mice that received treatment with α-PD-1 plus α-LAG3.
- Following rechallenge in the
opposite flank of the surviving mice, tumors implanted in those
previously treated with trilaciclib grew to a smaller volume and
regressed faster than controls, demonstrating the ability of
trilaciclib to strengthen memory T cell recall responses.
Data generated across multiple preclinical and clinical studies
to date indicate that trilaciclib has the greatest effect on longer
term endpoints including OS rather than earlier efficacy measures.
These new results contribute to the body of evidence suggesting
that preserving bone marrow and immune system function during
cytotoxic therapy and enhancing anti-tumor immunity and long-term
immune surveillance by increasing the generation of certain memory
T cells can allow patients to benefit while receiving trilaciclib,
and after trilaciclib discontinuation when receiving SACT.
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 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,"
"estimate," "intend" 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 protect the bone
marrow and immune system against the harmful effects of cytotoxic
therapy, leading to significantly improved survival outcomes among
patients who receive subsequent anticancer therapies and that
preservation of the lymphoid lineage and expanded memory T cell
pool are critical for long-term immune surveillance and eliciting
rapid recall responses, 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 RobertsVice President, Investor Relations & Corporate
Communications919-907-1944 wroberts@g1therapeutics.com
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