TCR2 Therapeutics Inc. (Nasdaq: TCRR), a clinical-stage
immunotherapy company with a pipeline of novel T cell therapies for
patients suffering from cancer, today announced positive interim
data from the ongoing Phase 1 portion of the TC-210 ( gavocabtagene
autoleucel or “gavo-cel”) Phase 1/2 clinical trial for
mesothelin-expressing solid tumors. As of the November 24, 2020
data cutoff, three PRs according to RECIST 1.1 criteria have been
recorded among the first eight patients treated on study, with our
first ovarian cancer patient having achieved a confirmed PR up to
month six. In addition, the first patient treated at a higher
gavo-cel dose (1x108/m2) without lymphodepletion achieved stable
disease through two months without any significant toxicities,
which has allowed patients to start treatment at that dose with the
addition of lymphodepletion. The toxicity profile remains
manageable with only two patients to date exhibiting
gavo-cel-related non-hematologic grade >2 toxicity and no
evidence of neurotoxicity or on-target, off-tumor toxicity.
Translational data further demonstrated TRuC-T cell expansion and
cytokine induction in all patients.
“Although the focus of any Phase 1 trial is
safety, the consistency in tumor regression and RECIST responses we
have observed with gavo-cel as a single agent supports our belief
in the advantages of TRuC-T cells over other cell therapies and the
potential for a fundamentally new approach in the treatment of
solid tumors,” said Garry Menzel, Ph.D., President and Chief
Executive Officer of TCR2 Therapeutics. “The HLA independence
of our technology allows us to treat a broad population of patients
with mesothelin surface expression while leveraging the full T cell
receptor complex to drive enhanced trafficking, on-target killing
and persistence in the hostile solid tumor microenvironment. Most
important, we are delivering clinical and survival benefit to those
patients with heavily pre-treated mesothelioma or ovarian
cancer.”
“The ability of gavo-cel to benefit patients who
have become treatment refractory after having failed multiple lines
of therapy, including immune checkpoint inhibitors and
anti-mesothelin therapy, combined with its manageable safety
profile is remarkable. The changes announced today to the Phase 1
trial design, reducing the intra-cohort safety observation periods
to 14 days from 28 days, enable us to more rapidly identify the
recommended Phase 2 dose and initiate the Phase 2 expansion trial
where we will evaluate the efficacy of gavo-cel in four solid tumor
indications. Importantly, in the Phase 2 we will explore the impact
of gavo-cel retreatment and its combination with checkpoint
inhibitor therapy which could further improve on the clinical
benefit observed to date,” said Alfonso Quintás-Cardama, M.D.,
Chief Medical Officer of TCR2 Therapeutics.
The primary objectives of the Phase 1 portion of
the study are to define the safety profile of gavo-cel in patients
whose tumors overexpress mesothelin and to determine the
recommended Phase 2 dose (RP2D). Secondary objectives include ORR
and disease control rate (DCR). Exploratory objectives include the
assessment of expansion, tumor infiltration, and persistence of
gavo-cel.
Summary of trial conduct, baseline
characteristics and gavo-cel
dose:
- Safety
Protocol: The new clinical trial protocol amendment allows
the intra-cohort safety observation periods to be reduced to 14
days from 28 days, allowing the testing of a gavo-cel dose over a
minimum of 56 days compared to the previous 84 days.
-
Screening: Forty-five percent of
patients met the mesothelin expression cut-off as defined per
protocol.
-
Manufacturing: Products meeting protocol defined
specifications for gavo-cel have been manufactured successfully for
each patient from whom apheresis material was sent into
production.
- Patient
Characteristics: Eight patients received gavo-cel
including seven with mesothelioma and one with ovarian cancer with
a median age of 65 years (range, 36-84 years). The median number of
prior therapies was 5.5 (range, 3-9), including immune checkpoint
inhibitor therapy (n=6) and anti-mesothelin therapies (n=3).
- Gavo-cel
Dose: The eight patients disclosed to date have received
gavo-cel at the following dose level (DL):
- DL
0: 5x107 cells/m2 without lymphodepletion – 1
mesothelioma
- DL
1: 5x107 cells/m2 following lymphodepletion – 5
mesothelioma and 1 ovarian cancer
- DL
2: 1x108 cells/m2 without lymphodepletion – 1
mesothelioma
Key clinical findings from the first
eight patients treated with gavo-cel:
-
Safety: Gavo-cel was generally well tolerated,
with no patients experiencing neurotoxicity or on-target, off-tumor
toxicities. Two (25%) patients experienced Cytokine Release
Syndrome (CRS) grade 3, which was successfully managed with
tocilizumab and corticosteroids.
- Clinical
Activity: All eight patients have had at least one disease
response assessment. The DCR was 100%, with all patients
experiencing tumor regression. The median decrease in the sum of
diameters of target lesions was 43% (range, 5% to 75%). The ORR was
38% (2 confirmed and 1 unconfirmed PRs) according to RECIST v1.1
criteria, including one patient who achieved a complete metabolic
response.
-
Translational Data: Peak gavo-cel expansion (Cmax)
occurred between days 7 and 23. Cmax increased when gavo-cel was
administered following lymphodepletion. The median peak gavo-cel
expansion was 811.9 copies/µg of genomic DNA (range, 520 to 5,901
copies/µg). Cytokine induction post-gavo-cel infusion was observed
in all evaluable patients, which is indicative of mesothelin target
engagement.
About the Phase 1/2 Clinical Trial in
Advanced Mesothelin-Expressing Solid Tumors
The Phase 1/2 clinical trial (NCT03907852) is
evaluating the safety and efficacy of gavocabtagene autoleucel
(“gavo-cel”; TC-210), TCR2’s T cell receptor fusion construct
directed against mesothelin. The trial is enrolling patients with
mesothelin expressing NSCLC, ovarian cancer, cholangiocarcinoma,
and malignant pleural/peritoneal mesothelioma. The Phase 1 dose
escalation portion of the clinical trial utilizes a modified 3+3
design with four increasing gavo-cel doses. At each dose,
gavo-cel will be tested in two separate dose levels: first without
lymphodepletion and then following lymphodepleting chemotherapy.
The Phase 1 portion of the clinical trial is ongoing.
In the Phase 2 portion of the clinical trial,
approximately 50 patients are planned to receive gavo-cel at
the RP2D in four distinct cohorts according to their cancer
diagnosis: NSCLC, ovarian cancer, malignant pleural/peritoneal
mesothelioma and cholangiocarcinoma. Each cohort will include ten
patients, except the NSCLC cohort which will include
20 patients with eight patients to receive gavo-cel as single
agent and 12 patients to receive gavo-cel in combination with a
programmed cell death 1 (PD-1) blocking antibody.
About Mesothelin-Expressing Solid
Tumors
Mesothelin is a cell-surface glycoprotein highly
expressed in a wide range of solid tumors, including malignant
pleural/peritoneal mesothelioma, ovarian cancer,
cholangiocarcinoma, breast cancer, pancreatic cancer and others.
Overexpression of mesothelin is associated with poorer prognosis in
some cancers due to its active role in both malignant
transformation and tumor aggressiveness by promoting cancer cell
proliferation, invasion, and metastasis. Of the wide range of solid
tumors expressing mesothelin, non-small cell lung cancer, ovarian
cancer, mesothelioma and cholangiocarcinoma represent a patient
population up to 80,000 annually in the United States alone.
TCR2
Therapeutics Conference Call and Webcast
TCR2 Therapeutics will host a conference call
and webcast on Monday, December 14th at 8:00am E.T. The webcast and
presentation will be made available on the TCR2 Therapeutics
website in the Investors section under Events at
http://investors.tcr2.com/events. Following the live audio webcast,
a replay will be available on the Company's website for
approximately 30 days.
About TCR2
Therapeutics
TCR2 Therapeutics Inc. is a
clinical-stage immunotherapy company developing a pipeline of novel
T cell therapies for patients suffering from solid tumors or
hematological malignancies. TCR2’s proprietary T cell
receptor (TCR) Fusion Construct T cells (TRuC®-T cells)
specifically recognize and kill cancer cells by harnessing
signaling from the entire TCR, independent of human leukocyte
antigens (HLA). In preclinical studies, TRuC-T cells have
demonstrated superior anti-tumor activity compared to chimeric
antigen receptor T cells (CAR-T cells), while secreting lower
levels of cytokine release. The Company’s lead TRuC-T cell product
candidate targeting solid tumors, gavo-cel, is currently being
studied in a Phase 1/2 clinical trial to treat patients with
mesothelin-positive non-small cell lung cancer (NSCLC), ovarian
cancer, malignant pleural/peritoneal mesothelioma, and
cholangiocarcinoma. The Company’s lead TRuC-T cell product
candidate targeting hematological malignancies, TC-110, is
currently being studied in a Phase 1/2 clinical trial to treat
patients with CD19-positive adult acute lymphoblastic leukemia
(aALL) and with aggressive or indolent non-Hodgkin lymphoma (NHL).
For more information about TCR2, please
visit www.tcr2.com.
Forward-looking Statements
This press release contains forward-looking
statements and information within the meaning of the Private
Securities Litigation Reform Act of 1995 and other federal
securities laws. The use of words such as "may," "will," "could",
"should," "expects," "intends," "plans," "anticipates," "believes,"
"estimates," "predicts," "projects," "seeks," "endeavor,"
"potential," "continue" or the negative of such words or other
similar expressions can be used to identify forward-looking
statements. These forward-looking statements include, but are not
limited to, express or implied statements regarding the therapeutic
potential of gavo-cel, future clinical development plans, the
development of the Company’s TRuC-T cells, their potential
characteristics, applications and clinical utility, and the
potential therapeutic applications of the Company’s TRuC-T cell
platform.
The expressed or implied forward-looking
statements included in this press release are only predictions and
are subject to a number of risks, uncertainties and assumptions,
including, without limitation: uncertainties inherent in clinical
studies and in the availability and timing of data from ongoing
clinical studies; whether interim results from a clinical trial
will be predictive of the final results of the trial; whether
results from preclinical studies or earlier clinical studies will
be predictive of the results of future trials; the expected timing
of submissions for regulatory approval or review by governmental
authorities, including review under accelerated approval processes;
orphan drug designation eligibility; regulatory approvals to
conduct trials or to market products; TCR2’s ability to maintain
sufficient manufacturing capabilities to support its research,
development and commercialization efforts, whether TCR2's cash
resources will be sufficient to fund TCR2's foreseeable and
unforeseeable operating expenses and capital expenditure
requirements, the impact of the COVID-19 pandemic on TCR2’s ongoing
operations; and other risks set forth under the caption "Risk
Factors" in TCR2’s most recent Annual Report on Form 10-K, most
recent Quarterly Report on Form 10-Q and its other filings with
the Securities and Exchange Commission. In light of these
risks, uncertainties and assumptions, the forward-looking events
and circumstances discussed in this press release may not occur and
actual results could differ materially and adversely from those
anticipated or implied in the forward-looking statements. You
should not rely upon forward-looking statements as predictions of
future events. Although TCR2 believes that the expectations
reflected in the forward-looking statements are reasonable, it
cannot guarantee that the future results, levels of activity,
performance or events and circumstances reflected in the
forward-looking statements will be achieved or occur.
Moreover, except as required by law, neither
TCR2 nor any other person assumes responsibility for the
accuracy and completeness of the forward-looking statements
included in this press release. Any forward-looking statement
included in this press release speaks only as of the date on which
it was made. We undertake no obligation to publicly update or
revise any forward-looking statement, whether as a result of new
information, future events or otherwise, except as required by
law.
Investor and Media Contact:
Carl MauchDirector, Investor Relations and
Corporate CommunicationsTCR2 Therapeutics Inc.(617)
949-5667carl.mauch@tcr2.com
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