- Poster published today at the 2021 American Association for
Cancer Research (AACR) Annual Meeting shows the GP2 final 5 year
immune response data from the Phase IIb clinical trial, concluding
that GP2 immunotherapy generated GP2-specific immune responses
leading to promising clinical benefit, thus supporting GP2’s
mechanism of action.
- The corresponding abstract can be viewed at the bottom of this
press release and the full poster, Figures 1-3, and an audio track
of the poster can be accessed or downloaded from the Clinical Trial
tab of the Company website:
https://greenwichlifesciences.com/clinical-trials/#Phase-IIb-AACR.
The audio track, given by Dr. Jaye Thompson, Vice President of
Clinical and Regulatory Affairs, can be directly played here:
https://greenwichlifesciences.com/wp-content/uploads/2021/04/Thompson-Ph2-AACR-2021.m4a.
- Immune responses to GP2 were measured over time using a CD8 T
cell dimer binding assay (Dimer Binding Assay) and
delayed-type-hypersensitivity (DTH) skin tests. The Dimer Binding
Assay detects the percentage of GP2 specific killer T cells that
can kill recurring cancer cells. The DTH skin test measures the
diameter of the skin immune response to GP2 in millimeters 48-72
hours after injection of GP2 without GM-CSF.
- Figure 1 of the poster shows that GP2 immunity peaked at 6
months in HER2 3+ patients after they completed their first 6
immunizations, as measured by the Dimer Binding Assay. The data
also shows that for the 2.5 years that the immune response was
measured, the immunity was sustained and remained above baseline,
resulting in 100% disease free survival (0% recurrence rate) over 5
years. In the placebo arm, the immune response was not as robust,
resulting in 89% disease free survival (11% recurrence rate).
- Figure 2 of the poster shows the same Dimer Binding Assay data
for HER2 3+ patients as in Figure 1, where the GP2 treated patients
showed statistically significant dimer readings versus baseline at
3, 6, and 12-13 months.
- Figure 3 of the poster shows that after completion of the 6th
immunization after 6 months, GP2 treated patients showed a robust
immune response using the DTH skin test, while the placebo did not
(p = 0.009). Within GP2-treated patients, the change from baseline
after 6 months was a median of 4.8 mm (mean of 11.6 mm), which was
a statistically significant increase over baseline (p < 0.0001).
This DTH data supports the Dimer Binding Assay data that shows a
peak immune response after 6 months.
Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the “Company”), a
clinical-stage biopharmaceutical company focused on the development
of GP2, an immunotherapy to prevent breast cancer recurrences in
patients who have previously undergone surgery, today presented a
poster of the final 5 year GP2 Phase IIb clinical trial immune
response data at the 2021 AACR Annual Meeting. Immune response is
the primary mechanism of action for GP2 and is critical to
developing dosing and booster treatment strategies that are
designed to achieve and sustain peak immunity, as well as to
prevent metastatic breast cancer recurrences.
This press release features multimedia. View
the full release here:
https://www.businesswire.com/news/home/20210410005045/en/
Figures 1-3 of Poster Presentation CT183
from 2021 AACR Annual Meeting Showing GP2 5 Year Immune Response
Data (Graphic: Business Wire)
It has been previously reported that the completion of the
GP2+GM-CSF Primary Immunization Series (PIS) reduced recurrence
rates to 0% over a 5 year follow-up period in HER2 3+ patients who
had received a standard course of trastuzumab after surgery. The
abstract and poster present the final immune response results over
the 5 year follow-up period, assessing peak immunity compared to
baseline and between patients treated with GP2+GM-CSF versus GM-CSF
alone, including by HER2 status.
Summary of the Final 5 Year Immune
Response Data as Previously Presented:
- Potent immune response data supports the previously reported
clinical outcome of 0% metastatic breast cancer recurrences over 5
years of follow up, if a patient completes the Primary Immunization
Series over the first 6 months of GP2 treatment.
- Statistically significant peak immunity was reached after 6
months of GP2 treatment as measured in both the Dimer Binding Assay
and the DTH skin test.
- HER2 3+ population immune response was similar to the HER2 1-2+
population immune response, suggesting the potential to treat the
HER2 1-2+ population (including triple negative breast cancer) with
GP2 immunotherapy in combination with trastuzumab (Herceptin) based
products and other clinically active agents.
- Broad based immune response suggests that GP2 immunotherapy and
Herceptin based products may also have the potential to treat other
HER2 1-3+ expressing cancers.
Dr. Thompson commented, “The analysis of the immune response
data in the Phase IIb trial provides mechanistic confirmation of
treatment effect correlated with the clinical response previously
reported. GP2 treated patients, independent of their HER2 status,
experienced a potent immune response to GP2, far greater than
patients treated with placebo. In addition, this data has provided
us with insight that will guide the upcoming Phase III trial. We
believe that monitoring immune response will be an important aspect
of the Phase III trial.”
Excerpts from the AACR Poster
CT183:
Title: Final five year median follow-up data from a
prospective, randomized, placebo-controlled, single-blinded,
multicenter, phase IIb study evaluating a time series of immune
responses using HER2/neu peptide GP2 + GM-CSF vs. GM-CSF alone
after adjuvant trastuzumab in HER2 positive women with operable
breast cancer
Each GP2 treated patient was scheduled to receive 6 intradermal
injections with GP2+GM-CSF over the first 6 months of treatment as
part of the Primary Immunization Series and 4 boosters every 6
months thereafter. Placebo patients received intradermal injections
with GM-CSF alone.
Immune responses to GP2 were measured over time using a CD8 T
cell dimer binding assay (Dimer Binding Assay) and
delayed-type-hypersensitivity (DTH) skin tests. The Dimer Binding
Assay detects the percentage of GP2 specific killer T cells that
can kill recurring cancer cells. The DTH skin test measures the
diameter of the skin immune response to GP2 in millimeters 48-72
hours after injection of GP2 without GM-CSF.
Figure 1 of the poster shows
that GP2 immunity peaked at 6 months in HER2 3+ patients after they
completed their first 6 immunizations, as measured by the Dimer
Binding Assay. The data also shows that for the 2.5 years that the
immune response was measured, the immunity was sustained and
remained above baseline, resulting in 100% disease free survival
(0% recurrence rate) over 5 years. In the placebo arm, the immune
response was not as robust, resulting in 89% disease free survival
(11% recurrence rate). Immune response in GP2-treated patients
increased quickly during the Primary Immunization Series and
remained statistically significantly above baseline for 6 months
after the completion of the Primary Immunization Series. Some
patients received boosters beginning at 12 months and the immune
response was assessed one month after the receiving the
booster.
Dimer Binding Assay: The
Dimer Binding Assay detects the percentage of GP2 specific killer T
cells that can kill recurring cancer cells. Ex vivo immune response
was assessed over 2.5 years with blood draws at baseline, then
after the 3rd and 6th immunizations in the Primary Immunization
Series, and then after each booster. Immune responses were assessed
by phenotypic clonal expansion assays in the majority of patients
(n=113). GP2-specific CTLs were quantified in patients treated with
GP2 using the Ig:A2 Dimer Assay and demonstrated an expansion over
time, showing an increase over baseline after the 3rd immunization
and remaining elevated for the entire course of follow-up.
Figure 2 of the poster shows
the same Dimer Binding Assay data for HER2 3+ patients as in Figure
1, where the GP2 treated patients showed statistically significant
dimer readings versus baseline (pre-vaccination) at 3, 6, and 12-13
months.
DTH Skin Test: The DTH skin
test measures the diameter of the skin immune response to GP2 in
millimeters, 48-72 hours after intradermal injection of GP2 without
GM-CSF. A DTH reaction was used to assess in vivo immune responses
in patients (n=150). The DTH orthogonal mean of the skin wheal was
measured 48-72 hours after injection using the sensitive
ballpoint-pen method and is compared using a Wilcoxon Rank-Sum. For
GP2 treated patients, there was a significant increase in DTH
reactions after the PIS compared to baseline DTH reactions.
Figure 3A shows that after
completion of the 6th immunization after 6 months, GP2 treated
patients showed a robust immune response using the DTH skin test,
while the placebo did not (p = 0.009). Within GP2 treated patients,
the change from baseline after 6 months was a median of 4.8 mm
(mean of 11.6 mm), which was a statistically significant increase
over baseline (p < 0.0001). The change from baseline in DTH at 6
months was more robust in the GP2 treated patients. Those patients
had an 11.6 mm mean increase in DTH after 6 months of exposure
while patients treated with GM-CSF alone had a 5.2 mm mean increase
(p = 0.023). This DTH data supports the Dimer Binding Assay data
that shows a peak immune response after 6 months.
Figure 3B shows that the DTH
immune response for GP2 treated patients was similarly robust in
HER2 3+ patients and HER2 1-2+ patients, independent of prior
trastuzumab treatment and HER2 expression levels. Thus, GP2’s
robust immune response in the HER2 1-2+ population suggests the
potential to apply GP2 immunotherapy to HER2 low to intermediate
expressing breast cancers, as well as to other HER2 1-3+ expressing
cancers.
AACR Abstract CT183:
Title: Final five year median follow-up data from a
prospective, randomized, placebo-controlled, single-blinded,
multicenter, phase IIb study evaluating a time series of immune
responses using HER2/neu peptide GP2 + GM-CSF vs. GM-CSF alone
after adjuvant trastuzumab in HER2 positive women with operable
breast cancer
Snehal S Patel, David B McWilliams, Mira S Patel, Christine T
Fischette, Jaye Thompson and F Joseph Daugherty.
Greenwich LifeSciences, Stafford, TX
Background: The final
analysis of the GP2 prospective, randomized, placebo-controlled,
single-blinded, multicenter Phase IIb trial (NCT00524277)
investigating GP2+GM-CSF versus GM-CSF alone in HLA-A02 patients
administered in the adjuvant setting to node-positive and high-risk
node-negative breast cancer patients with HER2 status (IHC 1-3+) is
now complete with 5 year follow-up. It has been previously reported
that completion of the GP2+GM-CSF Primary Immunization Series (PIS)
reduced recurrence rates to 0% over a 5 year follow-up period in
HER2 3+ patients, who received a standard course of trastuzumab
after surgery. Here we present the final immune response results,
assessing peak immunity compared to baseline and between GP2
treated patients versus placebo, including by HER2 status. Interim
analyses for this trial have been previously reported by Mittendorf
et al.
Methods: Each GP2-treated
patient was scheduled to receive 6 GP2+GM-CSF intradermal
injections over the first 6 months as part of the PIS and 4
GP2+GM-CSF booster intradermal injections every 6 months
thereafter. Placebo patients received GM-CSF only intradermal
injections. Immune responses to GP2 were measured over time using
delayed-type-hypersensitivity (DTH) skin tests and CD8 Tcell dimer
binding assays.
Results: This basket trial
explored HER2 3+ patients, who received a standard course of
trastuzumab after surgery, and HER2 1-2+ patients, who did not
receive trastuzumab after surgery. A DTH reaction was used to
assess in vivo immune responses in patients (n=145). The DTH
orthogonal mean was measured 48-72 hours after injection using the
sensitive ballpoint-pen method and are compared using a Wilcoxon
Rank-Sum. For GP2 treated patients, there was a significant
increase in DTH reactions after the PIS compared to baseline DTH
reactions. The DTH orthogonal mean in GP2 treated patients at
baseline had a median 0.0mm versus 10.8mm after the PIS. For
patients receiving GM-CSF alone, the DTH orthogonal mean prior to
and after the PIS had a median of 0.0mm. In addition, the DTH
reactions after the PIS were significantly greater in GP2 treated
patients than in placebo patients (10.8mm vs. 0.0mm, p=0.009) and
the DTH immune response in GP2 treated patients was similar between
HER2 3+ and HER2 1-2+ patients. Ex vivo immune responses were
assessed by phenotypic clonal expansion assays in the majority of
patients (n=114). GP2-specific CTLs were quantified using the Ig:A2
dimer assay and demonstrated a gradual expansion over time reaching
statistical significance approximately 6 months after the PIS
compared to baseline in the GP2 treated patients (n=53, p=0.010)
but not in the control patients (n=39, p=0.165).
Conclusions: Immunological
data comparing peak immunity to baseline and GP2 treated patients
to placebo showed that GP2 treated patients, independent of HER2
status, experienced a significant increase in their immune response
while those receiving GM-CSF only did not. Future studies may
explore the use of immune responses to assess: immunogenicity of
GP2 by HLA type, timing of boosters to sustain immunity, clinical
site performance, and the discontinuation of treatment for
non-responders.
About the AACR Annual Meeting 2021
The AACR is the first and largest cancer research organization
dedicated to accelerating the conquest of cancer and has more than
48,000 members residing in 127 countries and territories. The AACR
Annual Meeting program covers the latest discoveries across the
spectrum of cancer research — from population science and
prevention; to cancer biology, translational, and clinical studies;
to survivorship and advocacy — and highlights the work of the best
minds in research and medicine from institutions all over the
world.
About Breast Cancer and HER2/neu Positivity
One in eight U.S. women will develop invasive breast cancer over
her lifetime, with approximately 266,000 new breast cancer patients
and 3.1 million breast cancer survivors in 2018. HER2/neu (human
epidermal growth factor receptor 2) protein is a cell surface
receptor protein that is expressed in a variety of common cancers,
including in 75% of breast cancers at low (1+), intermediate (2+),
and high (3+ or over-expressor) levels.
About Greenwich LifeSciences, Inc.
Greenwich LifeSciences is a clinical-stage biopharmaceutical
company focused on the development of GP2, an immunotherapy to
prevent breast cancer recurrences in patients who have previously
undergone surgery. GP2 is a 9 amino acid transmembrane peptide of
the HER2/neu protein. In a randomized, single-blinded,
placebo-controlled, multi-center (16 sites led by MD Anderson
Cancer Center) Phase IIb clinical trial, no recurrences were
observed in the HER2/neu 3+ adjuvant setting after median 5 years
of follow-up, if the patient received the 6 primary intradermal
injections over the first 6 months (p = 0.0338). Of the 138
patients that have been treated with GP2 to date over 4 clinical
trials, GP2 treatment was well tolerated and no serious adverse
events were observed related to GP2 immunotherapy. Greenwich
LifeSciences is planning to commence a Phase III clinical trial
using a similar treatment regime as the Phase IIb clinical trial.
For more information on Greenwich LifeSciences, please visit the
Company’s website at www.greenwichlifesciences.com and follow the
Company's Twitter at https://twitter.com/GreenwichLS.
Forward-Looking Statement Disclaimer
Statements in this press release contain “forward-looking
statements” that are subject to substantial risks and
uncertainties. All statements, other than statements of historical
fact, contained in this press release are forward-looking
statements. Forward-looking statements contained in this press
release may be identified by the use of words such as “anticipate,”
“believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,”
“seek,” “may,” “might,” “plan,” “potential,” “predict,” “project,”
“target,” “aim,” “should,” "will,” “would,” or the negative of
these words or other similar expressions, although not all
forward-looking statements contain these words. Forward-looking
statements are based on Greenwich LifeSciences Inc.’s current
expectations and are subject to inherent uncertainties, risks and
assumptions that are difficult to predict, including statements
regarding the intended use of net proceeds from the public
offering; consequently, actual results may differ materially from
those expressed or implied by such forward-looking statements.
Further, certain forward-looking statements are based on
assumptions as to future events that may not prove to be accurate.
These and other risks and uncertainties are described more fully in
the section titled “Risk Factors” in the final prospectus related
to the public offering filed with the SEC. Forward-looking
statements contained in this announcement are made as of this date,
and Greenwich LifeSciences, Inc. undertakes no duty to update such
information except as required under applicable law.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20210410005045/en/
Company Contact Snehal Patel Investor Relations (832)
819-3232 info@greenwichlifesciences.com Investor & Public
Relations Contact for Greenwich LifeSciences Dave Gentry
RedChip Companies Inc. Office: 1-800-RED CHIP (733 2447) Cell:
(407) 491-4498 dave@redchip.com
Greenwich LifeSciences (NASDAQ:GLSI)
Historical Stock Chart
From Mar 2024 to Apr 2024
Greenwich LifeSciences (NASDAQ:GLSI)
Historical Stock Chart
From Apr 2023 to Apr 2024