MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company
focused on discovering, developing, manufacturing and
commercializing innovative antibody-based therapeutics for the
treatment of cancer, today presented updated efficacy and safety
results from the TAMARACK Phase 2 study of vobramitamab
duocarmazine (vobra duo), an antibody-drug conjugate (ADC) that
targets B7-H3, for patients with metastatic castration-resistant
prostate cancer (mCRPC). The data were featured in a poster
presentation at the European Society for Medical Oncology (ESMO)
Congress, taking place in Barcelona, Spain from September 13-17,
2024.
“A key reason for conducting the TAMARACK study was to test the
hypothesis that we could improve upon the duration of vobra duo
treatment observed in the Phase 1 study by reducing the starting
dose from 3.0 mg/kg to either 2.0 or 2.7 mg/kg and increasing the
dosing interval from every three weeks to every four weeks. In
doing so, our aim was to improve safety and tolerability, extend
the treatment duration and achieve improved rPFS as compared to the
result in our Phase 1 mCRPC dose expansion cohort,” said Scott
Koenig, M.D., Ph.D., President and CEO of MacroGenics. “We believe
that these latest results from TAMARACK continue to demonstrate
that vobra duo is an active drug in prostate cancer. Ultimately,
our path forward for the molecule will depend on the final safety
and efficacy data, including mature median rPFS, which we expect to
have in hand no later than early 2025. We expect to make decisions
about potential future development in the context of a competitive
treatment landscape assessment, resource allocation across our
clinical portfolio and potential partnering opportunities for vobra
duo.”
TAMARACK Study Demographics
The abstract submitted to ESMO was based on a data cut-off as of
April 12, 2024; updated data based on a cut-off date of July 9,
2024, are included below and are reported in the Company’s poster
presentation at ESMO.
The TAMARACK trial enrolled a total of 181 participants, with
176 participants receiving at least one dose of vobra duo at either
2.0 mg/kg q4W (n=90) or 2.7 mg/kg q4W (n=86). As of the data
cut-off date, 23 and 16 participants remained on treatment in the
2.0 mg/kg and 2.7 mg/kg cohorts, respectively. While mCRPC study
participants are no longer being dosed in the study, participants
continue to be monitored for adverse events, disease progression,
and survival.
Baseline Characteristics:
- Enrolled study participants had a median age of 70 years
(range, 35-89).
- 88 Study participants (48.6%) had an ECOG performance status of
1 or 2.
- 30 Study participants (16.6%) had visceral disease at baseline,
with liver or lung disease in 25 participants (13.8%).
- 81 Study participants (44.8%) had measurable disease at
baseline, and 97 (53.6%) had received prior taxane.
- Both treatment arms were well-balanced across most baseline
characteristics, including prior use of taxanes, androgen receptor
axis-targeted (ARAT) treatment, poly-ADP ribose polymerase (PARP)
treatment, and baseline PSA.
TAMARACK Efficacy Results as of July 9, 2024 Cut-off
Date
Overall, the Company believes that the results to date from the
TAMARACK study indicate antitumor activity associated with vobra
duo in mCRPC as demonstrated by the protocol-specified primary
endpoint of landmark 6-month radiographic progression-free survival
(rPFS) rate, as well as other measures of tumor response.
- In the intent-to-treat (ITT) population, 6-month rPFS rate was
69% for the 2.0 mg/kg arm (95% CI, 57-79) and 70% for the 2.7 mg/kg
arm (95% CI, 58-79).
- Landmark 6-month rPFS rates were consistent across taxane-naïve
study participants (ranging from 66-82%) and taxane pre-treated
study participants (ranging from 60-73%), regardless of treatment
arm.
- Although immature, with only 65 PFS events (35.9%) as of the
data cut-off, median rPFS was approximately 8.5 months for the
2.0 mg/kg cohort (95% CI, 7.2-11.2) and 7.5 months for the 2.7
mg/kg cohort (95% CI, 7.2-10.6). Because these results were
immature as of the cutoff date, they are likely to change as
additional events accrue.
Tumor response rates
- Out of 45 RECIST-response evaluable patients in the 2.0 mg/kg
arm, the confirmed objective response rate (ORR) was 20.0% (n=9)
and the unconfirmed ORR was 26.7% (n=12).
- Out of 32 RECIST-response evaluable patients in the 2.7 mg/kg
arm, the confirmed ORR was 40.6% (n=13) and the unconfirmed ORR was
46.9% (n=15).
- Confirmed ORR was comparable between taxane-naïve study
participants (26.7%, n=12/45) and taxane pre-treated study
participants (17.5%, n=11/63), regardless of treatment arm.
- Tumor responses did not appear to correlate with baseline B7-H3
expression based on archival tissue samples of mixed age.
TAMARACK Safety Results as of July 9, 2024 Cut-off
Date
Overall summary of adverse events (AEs)
- In the 2.0 mg/kg cohort, 65.6% of study participants (n=59)
experienced a Grade ≥3 treatment-emergent AE (TEAE); this cohort
had a discontinuation rate of 25.6% (n=23) and a dose reduction
rate of 50.0% (n=45) due to TEAEs.
- In the 2.7 mg/kg cohort, 62.8% of study participants (n=54)
experienced a Grade ≥3 TEAE; this cohort had a discontinuation rate
of 38.4% (n=33) and a dose reduction rate of 54.7% (n=47) due to
TEAEs.
- The most common (occurring in ≥20% of study participants)
all-grade TEAEs were: asthenia, edema peripheral, decreased
appetite, nausea, pleural effusion, diarrhea, fatigue,
constipation, anemia, palmar-plantar erythrodysesthesia (PPE, or
hand-foot syndrome), neutropenia, and stomatitis. The majority of
TEAEs with a ≥10% incidence rate in either treatment arm was
limited to Grade 1/2 events.
- Rates of pleural effusion, pericardial effusion, and PPE for
both the 2.0 mg/kg cohort (28.8%, 13.3%, 18.9%, respectively) and
the 2.7 mg/kg cohort (44.2%, 17.5%, 28%, respectively) decreased
compared to the Phase 1 mCRPC dose expansion cohort (48.8%, 17.1%,
46.3%, respectively), despite an increased median number of doses
of vobra duo administered on TAMARACK.
- Eight fatal treatment-related AEs as assessed by the treating
physician: five in the 2.0 mg/kg cohort and three in the 2.7mg/kg
cohort. These include three events of pneumonitis, and one event
each of cardiac failure, stress cardiomyopathy, ventricular
fibrillation, pleural effusion, and gastrointestinal
hemorrhage.
- Rates of treatment-related AEs (including all grades and Grade
≥3) and treatment-related severe AEs were similar between
taxane-naïve and taxane pre-treated study participants.
Tolerability findings
- In the 2.0 mg/kg cohort, 25.6% of study participants (n=23)
remained on study drug as of July 9, 2024. Study participants
received a median number of 6 doses (range, 1-11), with a median
dose intensity (calculated as a percentage of the total planned
dose that was administered) of 92.6% (range, 64.2-106.1%).
- In the 2.7 mg/kg cohort, 18.6% of study participants (n=16)
remained on study drug as of the data cut-off date. Study
participants received a median number of 6 doses (range, 1-12),
with a median dose intensity of 81.7% (range, 40.5-104.3%).
- Taxane-naïve study participants experienced higher rates of
dose reductions due to TEAEs (62.7%) and dose interruptions due to
TEAEs (70.7%) compared to taxane pre-treated study participants
(44.6% and 43.6%, respectively).
ESMO Poster Presentation
Title: TAMARACK: Randomized Phase 2 trial of the B7-H3
targeting antibody drug conjugate (ADC) vobramitamab duocarmazine
(vobra duo) in metastatic castration-resistant prostate cancer
(mCRPC)Presenter / Lead Author: Johann de Bono, M.D.,
M.Sc., Ph.D., FRCP, FMedSci, Division of Clinical Studies, Royal
Marsden Hospital Institute of Cancer Research, Sutton,
UKPresentation ID: 1654PSession Date: Sunday, September 15,
2024Poster Display Time: 9:00 a.m. – 5:00 p.m. CEST
The poster presentation is available for download under "Events
& Presentations" in the Investor Relations section of
MacroGenics’ website at http://ir.macrogenics.com/events.cfm.
Conference Call
The Company will host a conference call to discuss the
TAMARACK poster data and provide a general corporate update on
Monday, September 16, 2024, at 8:00am ET. The call will be led by
Scott Koenig, M.D., Ph.D., President and Chief Executive Officer;
Stephen Eck, M.D., Ph.D., Senior Vice President - Chief Medical
Officer; and Jim Karrels, Senior Vice President - Chief Financial
Officer.
To participate via telephone, please register in advance at this
link. Upon registration, all telephone participants will receive a
confirmation email detailing how to join the conference call,
including the dial-in number along with a unique passcode and
registrant ID that can be used to access the call. The listen-only
webcast of the conference call can be accessed under "Events &
Presentations" in the Investor Relations section of the Company's
website at http://ir.macrogenics.com/events.cfm. A recorded replay
of the webcast will be available shortly after the conclusion of
the call and archived on the Company's website for 30 days
following the call.
About Vobra Duo and the TAMARACK Study
Vobra duo is an antibody-drug conjugate (ADC) that targets
B7-H3, an antigen with broad expression across multiple solid
tumors and a member of the B7 family of molecules involved in
immune regulation. The TAMARACK Phase 2 study of vobra duo is being
conducted in participants with mCRPC who were previously treated
with one prior androgen receptor axis-targeted therapy (ARAT).
Participants may have received up to one prior taxane-containing
regimen, but no other chemotherapy agents. The TAMARACK study is
designed to evaluate vobra duo at two different doses: 2.0 mg/kg or
2.7 mg/kg every four weeks (q4W).
About MacroGenics, Inc.
MacroGenics (the Company) is a biopharmaceutical company focused
on discovering, developing, manufacturing and commercializing
innovative monoclonal antibody-based therapeutics for the treatment
of cancer. The Company generates its pipeline of product candidates
primarily from its proprietary suite of next-generation
antibody-based technology platforms, which have applicability
across broad therapeutic domains. The combination of MacroGenics'
technology platforms and protein engineering expertise has allowed
the Company to generate promising product candidates and enter into
several strategic collaborations with global pharmaceutical and
biotechnology companies. For more information, please see the
Company's website at www.macrogenics.com. MacroGenics and the
MacroGenics logo are trademarks or registered trademarks of
MacroGenics, Inc.
Cautionary Note on Forward-Looking
Statements
Any statements in this press release about future expectations,
plans and prospects for MacroGenics (“Company”), including
statements about the Company’s strategy, future operations,
clinical development of and regulatory plans for the Company’s
therapeutic candidates, expected timing of the release of final
safety and efficacy data, including mature median rPFS and other
statements containing the words “subject to”, "believe",
“anticipate”, “plan”, “expect”, “intend”, “estimate”, “potential,”
“project”, “may”, “will”, “should”, “would”, “could”, “can”, the
negatives thereof, variations thereon and similar expressions, or
by discussions of strategy constitute forward-looking statements
within the meaning of Section 27A of the Securities Act of 1933 and
Section 21E of the Securities Exchange Act of 1934. Actual results
may differ materially from those indicated by such forward-looking
statements as a result of various important factors, including:
risks that TZIELD, vobramitamab duocarmazine, lorigerlimab, ZYNYZ,
MARGENZA or any other product candidate’s revenue, expenses and
costs may not be as expected, risks relating to TZIELD,
vobramitamab duocarmazine, lorigerlimab, ZYNYZ, MARGENZA or any
other product candidate’s market acceptance, competition,
reimbursement and regulatory actions; future data updates,
especially timing and results of mature median radiographic
progression-free survival, other efficacy and safety data with
respect to vobramitamab duocarmazine; our ability to provide
manufacturing services to our customers; the uncertainties inherent
in the initiation and enrollment of future clinical trials; the
availability of financing to fund the internal development of our
product candidates; expectations of expanding ongoing clinical
trials; availability and timing of data from ongoing clinical
trials; expectations for the timing and steps required in the
regulatory review process; expectations for regulatory approvals;
expectations of future milestone payments; the impact of
competitive products; our ability to enter into agreements with
strategic partners and other matters that could affect the
availability or commercial potential of the Company's product
candidates; business, economic or political disruptions due to
catastrophes or other events, including natural disasters,
terrorist attacks, civil unrest and actual or threatened armed
conflict, or public health crises; costs of litigation and the
failure to successfully defend lawsuits and other claims against
us; and other risks described in the Company's filings with the
Securities and Exchange Commission. In addition, the
forward-looking statements included in this press release represent
the Company's views only as of the date hereof. The Company
anticipates that subsequent events and developments will cause the
Company's views to change. However, while the Company may elect to
update these forward-looking statements at some point in the
future, the Company specifically disclaims any obligation to do so,
except as may be required by law. These forward-looking statements
should not be relied upon as representing the Company's views as of
any date subsequent to the date hereof.
###
CONTACTS:
Jim Karrels, Senior Vice President, CFO
1-301-251-5172
info@macrogenics.com
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