TCR2 Therapeutics Inc. (Nasdaq: TCRR), a clinical-stage cell
therapy company with a pipeline of novel T cell therapies for
patients suffering from solid tumors, today announced positive
topline results from the Phase 1 portion of the gavo-cel Phase 1/2
clinical trial for mesothelin-expressing solid tumors, with some
patients still being monitored for clinical response or stable
disease.
As of the September 9, 2022 data cutoff, 32
patients (including 23 mesothelioma, eight ovarian cancer and one
cholangiocarcinoma) had received a single gavo-cel infusion in the
Phase 1 portion of the clinical trial. The patients were heavily
pretreated with a median of five prior lines of therapy, including
immune checkpoint inhibitors in 66% of patients and
mesothelin-directed therapies in 19% of patients. Following
identification of a dose-limiting toxicity (DLT) at dose level (DL)
5 (5x108 cells/m2 following lymphodepletion) in September 2021, the
study proceeded to a dose de-escalation portion, first at DL3.5
(3x108 cells/m2 following lymphodepletion) using a split-dosing
approach, and subsequently at DL3 (1x108 cells/m2 following
lymphodepletion) which was declared the recommended Phase 2 dose
(RP2D). No new DLTs were observed.
gavo-cel demonstrated a disease control rate
(DCR) of 77%, which is defined in the Phase 1 portion of the trial
as a response or sustained stable disease for at least three months
post infusion. As measured by blinded independent central review
(BICR), 28 of the 30 (93%) patients evaluable for efficacy
experienced tumor regression of their target lesions, ranging in
magnitude from 4% to 80%. Eight patients experienced target lesion
regression greater than 30%, six of whom (four with mesothelioma
and two with ovarian cancer) achieved a partial response (PR)
according to RECIST 1.1 criteria, including one patient who also
achieved a complete metabolic response. One patient with
cholangiocarcinoma was also considered to have achieved a PR by
investigator assessment, demonstrating that gavo-cel has induced
responses in every tumor type tested to date. The overall response
rate (ORR) among patients who received gavo-cel following
lymphodepletion chemotherapy was 22% by BICR and 26% by
investigator assessment. By BICR, the ORR was 21% among patients
with malignant pleural/peritoneal mesothelioma (MPM) and 29% among
those with ovarian cancer. The median overall survival (OS) for
patients with MPM was 11.2 months, whereas the median
progression-free survival (PFS) for patients with MPM was 5.6
months.
“We believe our Phase 1 clinical data already
position gavo-cel as a first- and best-in-class anti-mesothelin
monotherapy with a near-term opportunity during Phase 2 to further
improve the depth and durability of clinical benefit by using it in
combination with immune checkpoint inhibitors and redosing
strategies. These are remarkable data in the context of solid
tumors where there have been significant challenges with current
CAR-T therapies. I am particularly excited by this second RECIST
response in ovarian cancer as it supports the meaningful clinical
activity of gavo-cel in a large patient population. Additionally,
we continue to observe consistent tumor regression for heavily
pre-treated patients with mesothelioma for whom limited options are
available,” said Garry Menzel, Ph.D., President and Chief Executive
Officer of TCR2 Therapeutics. “As a result, we have narrowed
our focus in the short-term to our three core programs, gavo-cel,
TC-510 and TC-520, so that we can maximize the number of patients
with access to our investigational therapies.”
“The results of the Phase 1 trial underscore the
potential clinical value of gavo-cel in a very heavily pretreated
patient population that are receiving our engineered T cells as
their sixth line of therapy on average,” said Alfonso
Quintás-Cardama, M.D., Chief Medical Officer of
TCR2 Therapeutics. “gavo-cel has demonstrated a manageable
safety profile at the RP2D, induced RECIST responses in every
indication studied to date, and has provided a promising survival
signal among patients with mesothelioma as well as encouraging
preliminary efficacy data in ovarian cancer. These results clearly
support the further development of gavo-cel in the Phase 2 portion
of the study where we believe that the combination with checkpoint
inhibitors and the ability to retreat patients with additional
doses of gavo-cel will allow us to increase patients’ exposure to
gavo-cel, potentially translating into even higher response rates
and improved durability of benefit.”
“We have already dosed a number of patients in
combination with checkpoint inhibitors, including patients with
ovarian cancer, in the randomized Phase 2 portion of the trial and
look forward to providing ongoing progress updates on the various
arms of the study as well as following the remaining patients still
on the Phase 1 portion. We are clearly delighted that patients with
various cancers continue to derive meaningful benefit from
gavo-cel,” added Dr. Menzel.
The primary objectives of the Phase 1 portion of
the trial are to evaluate the safety profile of gavo-cel in
patients whose tumors overexpress mesothelin and to determine the
RP2D. Secondary objectives include ORR and 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:
- Screening:
Forty-eight percent of patients met the mesothelin expression
cutoff as defined per protocol.
- Patient
Characteristics: Thirty-two patients received gavo-cel
including 23 with mesothelioma, eight with ovarian cancer and one
with cholangiocarcinoma, with a median age of 63 years (range,
28-84 years). The median number of prior therapies was five (range
1-13), including immune checkpoint inhibitor therapy in 66% of
patients and mesothelin directed therapy in 19% of patients.
- gavo-cel Dose: The
32 patients disclosed to date have received gavo-cel at the
following DL:
- DL 0: 5x107
cells/m2 without lymphodepletion – one mesothelioma
- DL 1: 5x107
cells/m2 following lymphodepletion – seven mesothelioma and one
ovarian cancer
- DL 2: 1x108
cells/m2 without lymphodepletion – one mesothelioma
- DL 3: 1x108
cells/m2 following lymphodepletion – six mesothelioma, one
cholangiocarcinoma and six ovarian cancer
- DL 3.5: 3x108
cells/m2 following lymphodepletion - four mesothelioma and one
ovarian cancer
- DL 4: 5x108
cells/m2 without lymphodepletion – one mesothelioma
- DL 5: 5x108
cells/m2 following lymphodepletion – three mesothelioma
Key topline clinical findings from
patients treated with gavo-cel:
- Safety Data:
gavo-cel was generally well tolerated with a manageable adverse
event profile up to DL5. Over the course of the Phase 1 clinical
trial, two DLTs were observed: one case of Grade 3 pneumonitis at
DL1 that resolved with anti-cytokine therapy, and one case of Grade
5 bronchioalveolar hemorrhage at DL5. All three patients treated at
DL5 experienced severe cytokine release syndrome (CRS) which
resulted in the Safety Review Team recommending de-escalation. The
most frequent Grade 3 or higher non-hematological toxicity among
patients treated at the RP2D was CRS, which was reported in 15% of
patients.
- Clinical Activity:
Thirty patients were evaluable for response. DCR was 77%. Tumor
regression was observed in 28 (93%) patients. Eight patients
experienced target lesion regression greater than 30%, including
six patients who achieved a PR by RECIST criteria (four with MPM
and two with ovarian cancer). The ORR by RECIST criteria among
patients infused with gavo-cel following lymphodepletion
chemotherapy was 22% by BICR, which includes one patient who
achieved a complete metabolic response, and 26% by investigator
assessment, which includes an additional PR reported in a patient
with metastatic cholangiocarcinoma.
- Survival: Among
patients with mesothelioma, median OS and PFS were 11.2 months and
5.6 months, respectively, which compare favorably with the
published outcomes of patients with relapsed refractory MPM treated
in the second-line setting with standard therapy. Among patients
with ovarian cancer, median OS and PFS were 8.1 months and 5.8
months, respectively.
- Translational
Data: Peak gavo-cel expansion (Cmax) occurred between days
7 and 23. Cmax markedly increased when gavo-cel was
administered following lymphodepletion. Cytokine induction post
gavo-cel infusion was observed in all evaluable patients, which is
indicative of mesothelin target engagement. Post infusion,
expression of PD-1 was observed to be upregulated on circulating
gavo-cel T cells. Detection of gavo-cel in tumors and malignant
effusions showed higher expansion and longer persistence in these
tissues as compared to peripheral blood.
About the Phase 1/2 Clinical Trial in
Advanced Mesothelin-Expressing Solid TumorsThe Phase 1/2
clinical trial (NCT03907852) is evaluating the safety and efficacy
of gavocabtagene autoleucel (“gavo-cel”; previously known as
TC-210), TCR2’s T cell receptor fusion construct directed against
mesothelin. The trial is enrolling patients with either mesothelin
expressing non-small cell lung cancer (NSCLC), ovarian cancer,
cholangiocarcinoma, or malignant pleural/peritoneal mesothelioma
(MPM). The Phase 1 dose escalation portion of the clinical trial
utilized a modified 3+3 design with four increasing gavo-cel
doses. At each dose, gavo-cel was tested in two separate dose
levels: first without lymphodepletion and then following
lymphodepleting chemotherapy.
In the Phase 2 portion of the clinical trial,
patients will receive gavo-cel at the recommended Phase 2 dose
(1x108 cells/m2 following lymphodepletion). A total of 75
patients will be treated in the MPM cohort and a total of 20
patients will be treated in each one of the following indications:
ovarian, NSCLC and cholangiocarcinoma. In the MPM cohort, patients
will be randomized to receive either single agent gavo-cel,
gavo-cel in combination with OPDIVO® (nivolumab), or
gavo-cel in combination
with OPDIVO and YERVOY® (ipilimumab). Patients
enrolled in the ovarian cancer, NSCLC or cholangiocarcinoma cohorts
will all receive gavo-cel in combination with OPDIVO.
About Mesothelin-Expressing Solid
TumorsMesothelin 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 81,000 annually in the United States alone.
TCR2
Therapeutics Conference Call and WebcastTCR2
Therapeutics will host a conference call and webcast on Wednesday,
September 28, 2022 at 8:00am E.T. In order to participate in the
conference call, please register at https://bit.ly/3BTJ9Z7.
Participants can register via this link up to ten minutes prior to
start time. The webcast and presentation will be made available on
the TCR2 Therapeutics website in the Investors section under Events
at 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
TherapeuticsTCR2 Therapeutics Inc. is a
clinical-stage cell therapy company developing a pipeline of novel
T cell therapies for patients suffering from solid
tumors. The Company is focused on the discovery and
development of product candidates against novel and complex targets
utilizing its proprietary T cell receptor (TCR) Fusion
Construct T cells (TRuC®-T cells). The TRuC platform is
designed to specifically recognize and kill cancer cells by
harnessing signaling from the entire TCR, independent of human
leukocyte antigens (HLA). For more information about TCR2, please
visit www.tcr2.com.
Forward-looking
StatementsThis 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, TC-510 and TCR2’s
other product candidates, including potential improvements in
efficacy, safety and durability in the Phase 2 portion of the
gavo-cel trial, expectations regarding future growth and prospects,
future clinical development plans and anticipated timing of data
updates, 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 and topline 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, including
TCR2’s ability to secure additional manufacturing facilities;
TCR2’s ability to enroll patients in its clinical trials; 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 MauchSenior
Director, Investor Relations and Corporate Communications (617)
949-5667carl.mauch@tcr2.com
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