TCR2 Therapeutics Inc. (Nasdaq: TCRR), a clinical-stage cell
therapy company with a pipeline of novel T cell therapies for
patients suffering from cancer, today announced positive interim
results from the ongoing Phase 1 portion of the gavo-cel Phase 1/2
clinical trial for mesothelin-expressing solid tumors. A dataset
will also be featured in an oral presentation at the European
Society for Medical Oncology (ESMO) Congress 2021 on September 17
at 14:20 CEST (8:20am EST) (Presentation #959O) and is part of the
official ESMO Press Programme.
As of the June 30, 2021 data cutoff, 17 patients
(12 mesothelioma, 4 ovarian cancer and 1 cholangiocarcinoma) had
received a single gavo-cel infusion in the dose escalation portion
of the gavo-cel Phase 1 clinical trial. The median number of prior
lines of therapy was 5, including immune checkpoint inhibitors
(n=11) and mesothelin-directed therapies (n=5). Gavo-cel was
administered up to dose level 5 (DL5) (5x108/m2 following
lymphodepletion). Two dose limiting toxicities were reported: one
Grade 3 pneumonitis at DL1 that resolved with supportive measures,
which permitted the continuation of dose escalation, and one Grade
5 bronchoalveolar hemorrhage at DL5, which along with the
development of severe CRS in all 3 patients treated at this dose
level, led the Safety Review Team to declare 5x108/m2 as the MTD.
Following identification of the MTD, one patient has received
gavo-cel at 3x108/m2 after lymphodepletion using a split dosing
approach to refine the RP2D and an additional patient has been
treated at DL3 (1x108/m2 following lymphodepletion). In both cases
gavo-cel was well tolerated with only Grade 1 non-hematological
toxicities being reported.
15 of the 16 patients evaluable for efficacy
experienced regression of their target lesions, ranging in
magnitude from 5% to 75%. Six patients achieved partial responses
(PRs) by target lesion assessment, four of whom (3 with
mesothelioma and 1 with ovarian cancer) achieved a PR according to
RECIST 1.1 criteria, including one who also achieved a complete
metabolic response. One patient with cholangiocarcinoma was also
considered to have achieved a PR by investigator assessment, for an
ORR of 31%. By independent review assessment, the ORR was 25% with
a DCR Rate of 81%. The median overall survival for patients with
mesothelioma is 11.2 months, whereas the median progression free
survival is 5.9 months.
“The interim gavo-cel data reported today showed
continued clinical benefit and a manageable safety profile in a
population of patients that previously achieved minimal or no
improvement due to the advanced and aggressive state of their
cancer,” said principal investigator David Hong, M.D., deputy chair
of the Department of Investigational Cancer Therapeutics at The
University of Texas MD Anderson Cancer Center. “Patients with
treatment refractory cancer have very limited treatment options and
will often need hospice and supportive care. We are encouraged by
the early survival data from gavo-cel in patients previously
treated with checkpoint inhibitors and other therapies.”
“Our ambition with gavo-cel from the start was
to redefine treatment for solid tumors with cell therapies. We are
excited to present data demonstrating clinical activity in all
three mesothelin-expressing solid tumors treated to date and tumor
regression in a majority of patients who are treatment refractory
after numerous lines of therapy. We are very encouraged by the
progression free survival and overall survival observed among
patients with refractory mesothelioma treated so far with gavo-cel
in the Phase 1 trial,” said Alfonso Quintás-Cardama, M.D., Chief
Medical Officer of TCR2 Therapeutics. “Based on these data and
the most recent patient experiencing a very mild safety profile at
a cell dose of 3x108/m2, we believe the identification of the RP2D
is close at hand. As we approach the Phase 2 expansion phase, our
focus will shift to further optimizing outcomes for patients by
studying combinations with immune checkpoint inhibitors, allowing
gavo-cel re-treatment and evaluating different mesothelin
expression thresholds.”
The primary objectives of the Phase 1 portion of
the trial are to define 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-six percent of patients met
the mesothelin expression cut-off as defined per protocol.
- Patient
Characteristics: 17 patients received gavo-cel including
12 with mesothelioma, 4 with ovarian cancer and 1 with
cholangiocarcinoma with a median age of 57 years (range, 31-84
years). The median number of prior therapies was 5 (range, 1-9),
including immune checkpoint inhibitor therapy (n=11) and
anti-mesothelin therapies (n=5).
- Gavo-cel
Dose: The seventeen patients disclosed to date have
received gavo-cel at the following dose level (DL):
- DL
0: 5x107 cells/m2 without lymphodepletion – 1 mesothelioma
patient
- DL
1: 5x107 cells/m2 following lymphodepletion – 5
mesothelioma patients and 1 ovarian cancer patient
- DL
2: 1x108 cells/m2 without lymphodepletion – 1 mesothelioma
patient
- DL
3: 1x108 cells/m2 following lymphodepletion – 1
mesothelioma patient, 1 cholangiocarcinoma patient, and 3 ovarian
cancer patients
- DL
4: 5x108 cells/m2 without lymphodepletion – 1 mesothelioma
patient
- DL
5: 5x108 cells/m2 following lymphodepletion – 3
mesothelioma patients
Key clinical findings from patients
treated with gavo-cel:
-
Safety: gavo-cel was generally well tolerated with
a manageable adverse event profile with no patients experiencing
on-target, off-tumor toxicities. Two DLTs were observed: one case
of Grade 3 pneumonitis at DL1 that resolved with anti-cytokine
therapy, and one case of Grade 5 bronchoalveolar hemorrhage at DL5.
Furthermore, all three patients treated at DL5 experienced Grade ≥3
CRS which resulted in 5x108 cells/m2 following lymphodepletion
being declared the MTD.
- Clinical
Activity: 16 patients were evaluable for response. Tumor
regression was observed in 15 (94%) patients with a DCR of 81%. Six
patients achieved partial responses (PRs) by target lesion
assessment, four of whom (3 with mesothelioma and 1 with ovarian
cancer) achieved a PR according to RECIST 1.1 criteria. The ORR by
RECISTv1.1 criteria among patients infused with gavo-cel following
lymphodepletion chemotherapy was 31% by independent review
assessment, including one patient who achieved a complete metabolic
response, and 38% by investigator assessment, which included a PR
in a patient with metastatic cholangiocarcinoma.
-
Translational Data: Peak gavo-cel expansion (Cmax)
increased when gavo-cel was administered following lymphodepletion
in a dose dependent fashion. Cytokine elevations post-gavo-cel
infusion were 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
either mesothelin expressing non-small cell lung cancer (NSCLC),
ovarian cancer, cholangiocarcinoma, or 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.
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 Friday, September 17 at 9:00am E.T. In order to
participate in the conference call, please dial 866-220-8062
(domestic) or 470-495-9169 (international) and refer to
confirmation number 1597681. 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
Therapeutics
TCR2 Therapeutics Inc. is a
clinical-stage cell therapy company developing a pipeline of novel
T cell therapies for patients suffering from
cancer. 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 TCR2’s
expectations for the Phase 1/2 clinical trials of gavo-cel and
TC-110; TCR2’s expectations for the safety and efficacy of its
product candidates and enhancements, including gavo-cel and TC-110,
compared to current T-cell therapy approaches; TCR2’s expectations
regarding the timing of determining an RP2D for gavo-cel and TCR2’s
expectations regarding the estimated patient populations and
related market opportunities in gavo-cel’s and TC-110’s targeted
indications.
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 a trial; the possibility
that positive results from preclinical studies and correlative
studies may not necessarily be predictive of the results of TCR2’s
planned clinical trials, including the Phase 1/2 clinical trials of
gavo-cel and TC-110; the risk that the results from the Phase 1/2
clinical trials of gavo-cel and TC-110 will not support further
development and marketing approval; the risk that TCR2may be unable
to gain approval of gavo-cel, TC-110 and its other product
candidates on a timely basis, if at all; the risk that TCR2 has
over-estimated the potential patient population for its product
candidates, if approved; the risk that the current COVID-19
pandemic will impact TCR2’s clinical trials and other 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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