Immunocore presents Phase 1 data of
brenetafusp, an ImmTAC bispecific targeting PRAME, in patients with
ovarian cancer
Brenetafusp is clinically active as
monotherapy and in combination with chemotherapy in heavily
pre-treated, platinum-resistant ovarian cancer
patients
T cell fitness gene expression signature
in blood is an important parameter of clinical activity for
tebentafusp in uveal melanoma and for brenetafusp across different
tumor types
(OXFORDSHIRE, England & CONSHOHOCKEN, Penn.
& ROCKVILLE, Md., US, 14 September 2024) Immunocore Holdings
plc (Nasdaq: IMCR) (“Immunocore” or the “Company”), a
commercial-stage biotechnology company pioneering and delivering
transformative immunomodulating medicines to radically improve
outcomes for patients with cancer, infectious diseases and
autoimmune diseases, today presented Phase 1 data with brenetafusp
in patients with platinum resistant ovarian cancer at the 2024
European Society for Medical Oncology (ESMO) Congress. In a
proffered session to be held on Monday, September 16, 2024, the
Company will present translational Phase 1/2 data with KIMMTRAK®
(tebentafusp-tebn) and brenetafusp demonstrating that T cell
fitness gene expression signature in blood is an important
parameter associated with clinical activity for both therapies in
metastatic uveal melanoma.
“Brenetafusp monotherapy is active in heavily
pre-treated, platinum resistant ovarian cancer patients and can be
combined safely with chemotherapy. We see the hallmarks of ImmTAC
clinical activity in this Phase 1 data, such as disease control,
ctDNA molecular response, and association with T cell fitness,
which increases our confidence in the potential for brenetafusp in
ovarian cancer,” said David Berman, Head of Research and
Development. “While early, the promising efficacy data
from chemotherapy plus brenetafusp led us to expand the
combinations we are studying, including in earlier-line platinum
sensitive disease.”
Dr. Claire Friedman, Gynecologic Medical
Oncologist & Early Drug Development Specialist at Memorial
Sloan Kettering Cancer Center, said: “While many solid
tumors have benefited from the advances in immunotherapy, the
treatment of recurrent ovarian cancer has remained an ongoing
challenge. These data offer proof of concept that patients with
advanced, platinum-resistant ovarian cancer can benefit from
brenetafusp, alone or in combination with chemotherapy, and support
further development of the drug in this patient population.”
Phase 1 monotherapy data in heavily
pre-treated platinum resistant ovarian cancer patients
Thirty-seven patients with heavily pre-treated
(median 5 prior lines) serous ovarian cancer were treated with
brenetafusp monotherapy, including four patients previously
presented in the efficacy data set at ESMO 2022. A majority of
patients had received prior bevacizumab (81%) and PARP inhibitors
(59%).
Brenetafusp was well tolerated with no
treatment-related discontinuation or death observed. The most
frequent treatment-related adverse event was reversible and
manageable cytokine release syndrome, observed in 57% of patients,
with the majority being Grade 1.
Thirty-one of the 37 monotherapy patients were
evaluable for RECIST v1.1 tumor assessment, 58% of whom
demonstrated disease control (partial response and stable disease),
including two confirmed partial responses (6.5% RECIST response
rate). Of patients who had tumor progression, 64% were treated
beyond progression (median of 2 additional months). Across all 37
patients, the median progression-free survival (PFS) was 3.3
months, and the overall survival (OS), while still maturing, was
73% at 6 months.
Of the 29 monotherapy patients evaluable for
circulating tumor DNA (ctDNA) response, 31% (9/29) had a molecular
response (≥0.5 log reduction by week 9).
Twenty-eight monotherapy patients were evaluable
for baseline blood T cell fitness (TCF) gene expression signature.
There was greater activity in patients with a TCF signature above
median versus those at or below the median, respectively,
including: disease control (80% vs 38%), PFS (3.7 months vs 2.2
months) and six-month OS (93% vs 47%).
Phase 1 chemotherapy combination data in
heavily pre-treated platinum resistant ovarian cancer
patients
As presented today at ESMO in a pre-clinical
study poster (1021P), the combination of chemotherapy with
brenetafusp has the potential to enhance clinical activity by
increasing expression of the antigen presentation machinery in
cancer cells.
In the Phase 1 trial, 16 patients with
platinum-resistant ovarian cancer were treated with brenetafusp and
either gemcitabine, nab-paclitaxel or pegylated doxorubicin
chemotherapy. These patients were heavily pre-treated (median of 4
prior treatment lines) including prior bevacizumab (75%) and PARP
inhibitors (75%). The safety profile of brenetafusp in combination
with chemotherapy was consistent with the expected profile of each
individual agent.
Thirteen of the 16 combination patients were
evaluable for RECIST v1.1 tumor assessment. All 13 patients
received prior platinum and taxane therapy, and 6 received prior
gemcitabine. Sixty nine percent (9/13) of patients achieved disease
control, including three partial responses (23% RECIST response
rate). Historical chemotherapy efficacy data in this heavily
pre-treated patient population is sparse but indicate response
rates are less than 10%, with disease control rates typically
~40-50%1.
Eleven of the 16 combination patients were
evaluable for ctDNA response. The molecular response rate was 82%
(9/11). As previously reported for brenetafusp in cutaneous
melanoma (ASCO 2024), ctDNA molecular response in this trial was
also associated with longer OS and PFS.
T cell fitness associated with clinical
benefit across ImmTAC platform and in different tumor
types
At an oral proffered session on Monday,
September 16, 2024, the Company will present translational data
from previously treated, metastatic uveal melanoma (mUM) patients,
including 132 patients treated with KIMMTRAK in a Phase 1/2 trial,
and 22 patients treated with brenetafusp in a Phase 1 trial.
In the KIMMTRAK cohort, patients with a TCF
signature greater than or equal to the median had higher clinical
activity compared to patients with a TCF signature below the
median, respectively, including longer OS (28 months vs 11 months),
PFS (5 months vs 2 months) and disease control (67% vs 36%). The
association of TCF signature with longer OS was independent of
known prognostic factors in uveal melanoma. In addition, the TCF
signature was associated with greater tumor reduction and a higher
rate of on-target, melanocyte-related adverse events; both are
consistent with the mechanism of action, and suggest that the
signature is not purely prognostic.
This TCF signature, discovered for KIMMTRAK in
mUM, was subsequently confirmed as an important parameter of
clinical activity for brenetafusp in mUM (ESMO 2024), ovarian
cancer (ESMO 2024), and cutaneous melanoma (ASCO 2024). The
accumulating data suggests that ImmTAC therapies may deliver
greater clinical activity in earlier line patients, where TCF is
expected to be higher, leading the Company to investigate
brenetafusp in these populations.
About ImmTAC®
molecules for cancer
Immunocore’s proprietary T cell receptor (TCR)
technology generates a novel class of bispecific biologics called
ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules
that are designed to redirect the immune system to recognize and
kill cancerous cells. ImmTAC molecules are soluble TCRs engineered
to recognize intracellular cancer antigens with ultra-high affinity
and selectively kill these cancer cells via an anti-CD3
immune-activating effector function. Based on the demonstrated
mechanism of T cell infiltration into human tumors, the ImmTAC
mechanism of action holds the potential to treat hematologic and
solid tumors, regardless of mutational burden or immune
infiltration, including immune “cold” low mutation rate tumors.
About the IMC-F106C-101 Phase 1/2
trial
IMC-F106C-101 is a first-in-human, Phase 1/2
dose escalation trial in patients with multiple solid tumor cancers
including non-small cell lung cancer (NSCLC), small-cell lung
cancer (SCLC), endometrial, ovarian, cutaneous melanoma, and breast
cancers. The Phase 1 dose escalation trial was designed to
determine the maximum tolerated dose (MTD), as well as to evaluate
the safety, preliminary anti-tumor activity and pharmacokinetics of
IMC-F106C (brenetafusp), a bispecific protein built on Immunocore’s
ImmTAC technology, and the Company’s first molecule to target the
PRAME antigen. The Company is enrolling patients into three
expansion arms in ovarian, NSCLC, and endometrial cancers. The
IMC-F106C-101 trial is adaptive and includes the option for Phase 2
expansion, allowing for approximately 100 patients treated per
tumor type in the Phase 1 and 2 expansion arms. Dose escalation
continues in additional solid tumors as well as plans for
combination arms with standards-of-care, including checkpoint
inhibitors, chemotherapy, and tebentafusp.
About Ovarian Cancer
Most patients with ovarian cancer are diagnosed
with advanced disease, giving it the highest mortality amongst
gynecological malignancies in the US and Europe. The current
standard of care is surgery followed by platinum-based
chemotherapy, and although many patients initially respond, the
disease often recurs and, over time, becomes resistant to further
platinum therapy. There is significant unmet need for new therapies
that improve clinical outcomes in both platinum-sensitive and
platinum-resistant ovarian cancer patients.
About Uveal Melanoma
Uveal melanoma is a rare and aggressive form of
melanoma affecting the eye. Although it is the most common primary
intraocular malignancy in adults, the diagnosis is rare, and up to
50% of people with uveal melanoma will eventually develop
metastatic disease. Unresectable or metastatic uveal melanoma
typically has a poor prognosis and had no approved treatment until
KIMMTRAK.
About
KIMMTRAK®
KIMMTRAK is a novel bispecific protein comprised
of a soluble T cell receptor fused to an anti-CD3 immune-effector
function. KIMMTRAK specifically targets gp100, a lineage antigen
expressed in melanocytes and melanoma. This is the first molecule
developed using Immunocore’s ImmTAC technology platform designed to
redirect and activate T cells to recognize and kill tumor cells.
KIMMTRAK has been approved for the treatment of
HLA-A*02:01-positive adult patients with unresectable or metastatic
uveal melanoma in the United States, European Union, Canada,
Australia, and the United Kingdom.
IMPORTANT SAFETY
INFORMATION
Cytokine Release Syndrome (CRS), which may be
serious or life-threatening, occurred in patients receiving
KIMMTRAK. Monitor for at least 16 hours following first three
infusions and then as clinically indicated. Manifestations of CRS
may include fever, hypotension, hypoxia, chills, nausea, vomiting,
rash, elevated transaminases, fatigue, and headache. CRS occurred
in 89% of patients who received KIMMTRAK with 0.8% being grade 3 or
4. Ensure immediate access to medications and resuscitative
equipment to manage CRS. Ensure patients are euvolemic prior to
initiating the infusions. Closely monitor patients for signs or
symptoms of CRS following infusions of KIMMTRAK. Monitor fluid
status, vital signs, and oxygenation level and provide appropriate
therapy. Withhold or discontinue KIMMTRAK depending on persistence
and severity of CRS.
Skin Reactions
Skin reactions, including rash, pruritus, and
cutaneous edema occurred in 91% of patients treated with KIMMTRAK.
Monitor patients for skin reactions. If skin reactions occur, treat
with antihistamine and topical or systemic steroids based on
persistence and severity of symptoms. Withhold or permanently
discontinue KIMMTRAK depending on the severity of skin
reactions.
Elevated Liver Enzymes
Elevations in liver enzymes occurred in 65% of
patients treated with KIMMTRAK. Monitor alanine aminotransferase
(ALT), aspartate aminotransferase (AST), and total blood bilirubin
prior to the start of and during treatment with KIMMTRAK. Withhold
KIMMTRAK according to severity.
Embryo-Fetal Toxicity
KIMMTRAK may cause fetal harm. Advise pregnant
patients of potential risk to the fetus and patients of
reproductive potential to use effective contraception during
treatment with KIMMTRAK and 1 week after the last dose. The most
common adverse reactions (≥30%) in patients who received KIMMTRAK
were cytokine release syndrome, rash, pyrexia, pruritus, fatigue,
nausea, chills, abdominal pain, edema, hypotension, dry skin,
headache, and vomiting. The most common (≥50%) laboratory
abnormalities were decreased lymphocyte count, increased
creatinine, increased glucose, increased AST, increased ALT,
decreased hemoglobin, and decreased phosphate. For more
information, please see full Summary of Product Characteristics
(SmPC) or full U.S. Prescribing Information (including BOXED
WARNING for CRS).
About KIMMTRAKConnect
Immunocore is committed to helping patients who
need KIMMTRAK obtain access via our KIMMTRAKConnect program. The
program provides services with dedicated nurse case managers who
provide personalized support, including educational resources,
financial assistance, and site of care coordination. To learn more,
visit KIMMTRAKConnect.com or call 844-775-2273.
About Immunocore
Immunocore is a commercial-stage biotechnology
company pioneering the development of a novel class of TCR
bispecific immunotherapies called ImmTAX – Immune mobilizing
monoclonal TCRs Against X disease – designed to treat a broad range
of diseases, including cancer, autoimmune diseases, and infectious
diseases. Leveraging its proprietary, flexible, off-the-shelf
ImmTAX platform, Immunocore is developing a deep pipeline in
multiple therapeutic areas, including nine active clinical and
pre-clinical programs in oncology, infectious diseases, and
autoimmune diseases. The Company’s most advanced oncology TCR
therapeutic, KIMMTRAK has been approved for the treatment of
HLA-A*02:01-positive adult patients with unresectable or metastatic
uveal melanoma in the United States, European Union, Canada,
Australia, and the United Kingdom.
Forward Looking Statements
This press release contains “forward-looking
statements” within the meaning of the safe harbor provisions of the
Private Securities Litigation Reform Act of 1995. Words such as
“may”, “will”, “believe”, “expect”, “plan”, “anticipate” and
similar expressions (as well as other words or expressions
referencing future events or circumstances) are intended to
identify forward-looking statements. All statements, other than
statements of historical facts, included in this press release are
forward-looking statements. These statements include, but are not
limited to, statements regarding expected clinical benefits of
ImmTAC molecules, including KIMMTRAK, brenetafusp, and the
Immunocore’s other product candidates, including disease control,
including partial responses, ctDNA molecular response, progression
free survival and extended overall survival benefit, tumor
reduction, and the potential to enhance clinical activity by
increasing expression of the antigen presentation machinery in
cancer cells; and expectations regarding the design, progress,
timing, enrollment, randomization, scope, expansion, funding and
results of the IMC-F106C-101 Phase 1/2 dose escalation trial with
brenetafusp in patients with ovarian cancer. Any forward-looking
statements are based on management’s current expectations and
beliefs of future events and are subject to a number of risks and
uncertainties that could cause actual events or results to differ
materially and adversely from those set forth in or implied by such
forward-looking statements, many of which are beyond the Company’s
control. These risks and uncertainties include, but are not limited
to, the impact of worsening macroeconomic conditions on the
Company’s business, financial position, strategy and anticipated
milestones, including Immunocore’s ability to conduct ongoing and
planned clinical trials; Immunocore’s ability to obtain a clinical
supply of current or future product candidates or commercial supply
of KIMMTRAK or any future approved products, including as a result
of health epidemics or pandemics, war in Ukraine, the conflict
between Hamas and Israel, or global geopolitical tension;
Immunocore’s ability to obtain and maintain regulatory approval of
its product candidates, including KIMMTRAK; Immunocore’s ability
and plans in continuing to establish and expand a commercial
infrastructure and to successfully launch, market and sell KIMMTRAK
and any future approved products; Immunocore’s ability to
successfully expand the approved indications for KIMMTRAK or obtain
marketing approval for KIMMTRAK in additional geographies in the
future; the delay of any current or planned clinical trials,
whether due to patient enrollment delays or otherwise; Immunocore’s
ability to successfully demonstrate the safety and efficacy of its
product candidates and gain approval of its product candidates on a
timely basis, if at all; competition with respect to market
opportunities; unexpected safety or efficacy data observed during
preclinical studies or clinical trials; actions of regulatory
agencies, which may affect the initiation, timing and progress of
clinical trials or future regulatory approval; Immunocore’s need
for and ability to obtain additional funding, on favorable terms or
at all, including as a result of worsening macroeconomic
conditions, including changes in inflation and interest rates and
unfavorable general market conditions, and the impacts thereon of
the war in Ukraine, the conflict between Hamas and Israel, and
global geopolitical tension; Immunocore’s ability to obtain,
maintain and enforce intellectual property protection for KIMMTRAK
or any of its product candidates it or its collaborators are
developing; and the success of Immunocore’s current and future
collaborations, partnerships or licensing arrangements, including
the risk that Immunocore may not realize the anticipated benefits
of its collaboration with Bristol Myers Squibb. These and other
risks and uncertainties are described in greater detail in the
section titled "Risk Factors" in Immunocore’s filings with the
Securities and Exchange Commission, including Immunocore’s most
recent Annual Report on Form 10-K for the year ended December 31,
2023 filed with the Securities and Exchange Commission on February
28, 2024, as well as discussions of potential risks, uncertainties,
and other important factors in the Company’s subsequent filings
with the SEC. All information in this press release is as of the
date of the release, and the Company undertakes no duty to update
this information, except as required by law.
Contact Information
Immunocore
Sébastien Desprez, Head of CommunicationsT: +44
(0) 7458030732E: sebastien.desprez@immunocore.comFollow on Twitter:
@Immunocore
Investor Relations
Clayton Robertson, Head of Investor RelationsT:
+1 (215) 384-4781E: ir@immunocore.com
1 Average based on Liu 2016, Lheureux 2021 &
Griffiths 2011
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