Immunocore reports updated Phase 1 data of
brenetafusp (IMC-F106C), an ImmTAC bispecific targeting PRAME, in
immune checkpoint pre-treated cutaneous melanoma patients at ASCO
2024
Monotherapy brenetafusp (IMC-F106C) in
late-line cutaneous melanoma demonstrated promising disease control
(partial response and stable disease), progression free survival
(PFS), and ctDNA molecular response
Clinical activity was enriched in PRAME
positive patients with 58% disease control rate and 4.2 months
median PFS
Peripheral blood T cell fitness was
associated with increased brenetafusp clinical activity and was
higher in earlier lines of therapy
Brenetafusp is well tolerated as
monotherapy and in combination with anti-PD1
Currently screening patients in a Phase 3
clinical trial (PRISM-MEL-301) of brenetafusp with nivolumab in
first-line advanced cutaneous melanoma
Company to host a live webcast and
conference call today at 7:15 PM ET / 6:15 PM CT
(OXFORDSHIRE, England & CONSHOHOCKEN, PA
& ROCKVILLE, MD, US, 31 May 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 released Phase 1 data with the first off-the-shelf ImmTAC®
targeting PRAME, brenetafusp (IMC-F106C), in patients with
late-line, post-checkpoint cutaneous melanoma. Brenetafusp was
shown to be well tolerated, in monotherapy and in combination with
anti-PD1, and demonstrated durable clinical benefit.
“Brenetafusp continues to demonstrate promising
monotherapy clinical activity in late-line cutaneous melanoma
patients who were previously treated with checkpoint therapies,”
said Dr. Omid Hamid, Chief, Translational
Research and Immunotherapy, Co-Director, Melanoma Therapeutics at
Cedars-Sinai Cancer at the Angeles Clinic and Research
Institute. “The disease control and PFS benefit for these
brenetafusp-treated melanoma patients compares favorably to data
with other immunotherapies.”
“The best measure of brenetafusp monotherapy
activity is disease control, which is observed in 56% of checkpoint
pre-treated melanoma patients,” said David Berman, Head of
Research and Development. “We expect brenetafusp PFS to be
even higher in first-line based on our analysis of blood T cell
fitness. These data points, in conjunction with the significant
molecular response and the expected additive benefit of combining
with an active anti-PD1, provide confidence for PFS as an endpoint
in our ongoing Phase 3 first-line trial.”
Phase 1 data in post-checkpoint
cutaneous melanoma
As of 18 March 2024, 47 patients have received
brenetafusp (IMC-F106C) monotherapy at clinically active target
dose levels. All monotherapy treated patients had received prior
immune checkpoint inhibitors (100% anti-PD1, 81% anti-CTLA4). PRAME
expression was high amongst evaluable patients (median H score of
215). Only 11% of patients had PRAME negative tumors, as measured
by immunohistochemistry.
Brenetafusp was well-tolerated, with
treatment-related adverse events (TRAEs) that were manageable and
consistent with the mechanism of action. The most frequent TRAE
reported was Grade 1 or 2 cytokine release syndrome (CRS) and rash;
these events occurred predominantly following the initial three
doses. There were no Grade 3 or higher CRS TRAEs.
Of the 47 monotherapy patients, 36 had a RECIST
evaluable tumor assessment. The disease control rate (DCR),
consisting of partial response (PR) and stable disease (SD), was
56% including 4 PR (ORR 11%) and 16 SD (44%). Durable tumor
reduction, confirmed by at least one subsequent scan, was observed
in 28% of patients and is an attribute of the ImmTAC platform1.
Clinical benefit was enriched in the 31 evaluable PRAME positive
patients. The DCR in this group was 58% and included all 10
patients (32%) with confirmed tumor reduction.
Both median progression free survival (mPFS) and
6-month overall survival (OS) rates were greater in PRAME positive
than in PRAME negative monotherapy patients: 4.2 vs 2.1 months and
95% vs 40%, respectively.
42% of ctDNA-evaluable, PRAME positive
monotherapy patients had a molecular response (10/24) and there was
a trend for longer PFS and OS in molecular responders. No
ctDNA-evaluable PRAME negative patients had ctDNA reduction.
In addition to the monotherapy patients treated
with brenetafusp, there were 9 cutaneous melanoma patients who
received brenetafusp in combination with an anti-PD1
(pembrolizumab), all of whom had received prior checkpoint
inhibitors (100% prior anti-PD1, 89% prior CTLA4). Overall,
patients were more heavily pre-treated in the combination cohort
compared to monotherapy (median prior lines: 4 vs 2; PD-1
refractory: 67% vs 30%). Brenetafusp in combination with
pembrolizumab was well tolerated, with TRAEs that were manageable
and consistent with the mechanism of action of both agents. There
was one dose-limiting toxicity (transaminitis) reported in one
patient with prior history of checkpoint inhibitor induced
autoimmune hepatitis.
Of the 7 patients evaluable for efficacy in
combination, 4 achieved disease control including 1 ongoing PR
(confirmed after the data cut off for the presentation), and 3 of
the 4 ctDNA evaluable patients having molecular response.
In 41 gene-expression evaluable monotherapy
patients, a gene signature was identified from baseline peripheral
blood that was a measure of systemic T cell fitness. Patients with
gene signature expression levels greater than or equal to the
median had higher clinical benefit including a median PFS of 6
months and DCR of 69%, compared to those with less than the median
gene expression levels (2 months and 42%, respectively). Patients
with only 1-2 prior lines of therapy had higher T cell fitness gene
signature, on average, than those with 3 or more prior lines of
therapy.
The advanced cutaneous melanoma data from the
ongoing Phase 1/2 trial of brenetafusp will be presented today at
2:45 PM CT / 3:45 PM ET, in the Melanoma/Skin Cancers oral abstract
session at the 2024 American Society of Oncology (ASCO) Annual
Meeting. The presentation will be accessible in the ‘Events &
Presentations’ section of the Investor Relations section of the
Company’s website.
PRISM-MEL-301 – First PRAME Phase 3
clinical trial with brenetafusp in first-line advanced cutaneous
melanoma
The Company is enrolling patients in a
registrational Phase 3 clinical trial with brenetafusp in
first-line advanced cutaneous melanoma (CM) with a primary endpoint
of progression-free survival (PFS) (NCT06112314). The trial will
randomize HLA-A*02:01-positive, first-line advanced CM patients to
brenetafusp + nivolumab versus a control arm of either nivolumab or
nivolumab + relatlimab, depending on the country where the patient
is enrolled.
Under the terms of a clinical trial
collaboration and supply agreement, Immunocore will sponsor and
fund this registrational Phase 3 clinical trial, and Bristol Myers
Squibb will provide nivolumab.
Audio Webcast
Immunocore will host a conference call today,
May 31, 2024 at 7:15 PM ET / 6:15 PM CT, to discuss the Phase 1
PRAME expansion data and Phase 3 registrational trial in cutaneous
melanoma. The call will also be available via webcast by visiting
the Events & Presentations section on Immunocore’s website. A
replay of this webcast will be available for 30 days.
Conference Call Details:U.S. (toll-free):
877-405-1239International (toll): +1 201-389-0851
###
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 PRISM-MEL-301 – Phase 3 trial with
brenetafusp (IMC-F106C; PRAME-A02) in 1L advanced cutaneous
melanoma
The Phase 3 registrational trial will randomize
patients with previously untreated, HLA-A*02:01-positive, advanced
melanoma to brenetafusp + nivolumab versus nivolumab or nivolumab +
relatlimab, depending on the country where the patient is enrolled.
The study will initially randomize to three arms: two brenetafusp
dose regimens (40 mcg and 160 mcg) and control arm and will
discontinue one of the brenetafusp dose regimens after an initial
review of the first 60 patients randomized to the two experimental
arms (90 patients randomized total). The primary endpoint of the
trial is progression free survival (PFS) by blinded independent
central review (BICR), with secondary endpoints of overall survival
(OS) and overall response rate (ORR).
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 has initiated patient enrollment into
four expansion arms in cutaneous melanoma, ovarian, NSCLC, and
endometrial carcinomas. 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. Ph1 monotherapy continues in additional solid
tumors as well as multiple combinations with standards-of-care,
including checkpoint inhibitors, chemotherapy, targeted therapies,
and tebentafusp.
About Cutaneous Melanoma
Cutaneous melanoma (CM) is the most common form
of melanoma. It is the most aggressive skin carcinoma and is
associated with the vast majority of skin cancer-related
mortality. The majority of patients with CM are diagnosed
before metastasis and survival remains poor for the large
proportion of patients with metastatic disease. Despite recent
progress in advanced melanoma therapy, there is still an unmet need
for new therapies that improve first-line response rates
and duration of response as well as for patients who are
refractory to first-line treatments.
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 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, and infectious disease.
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,”
“estimate,” 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 the expected clinical
benefits of ImmTAC molecules, including KIMMTRAK, brenetafusp, and
the Immunocore’s other product candidates, including tumor
reduction, disease control rate of partial responses and stable
diseases, ctDNA molecular response, progression free survival and
extended overall survival benefit, alone and in combination with
other therapies; the expected efficacy and tolerability of
Immunocore’s products and product candidates, including
brenetafusp; expectations regarding receipt of regulatory approvals
and completion of related procedures; the value proposition of
Immunocore’s products and product candidates, including KIMMTRAK
and brenetafusp; future development plans of Immunocore’s products
and product candidates, including KIMMTRAK and brenetafusp; and
expectations regarding the design, progress, timing, enrollment,
randomization, scope, expansion, funding and results of
Immunocore’s existing and planned clinical trials, including the
Phase 3 PRISM-MEL301 trial with brenetafusp plus nivolumab versus
standard nivolumab in 1L advanced cutaneous melanoma and the
IMC-F106C-101 Phase 1/2 dose escalation trial with brenetafusp 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, and those of the
Immunocore’s collaboration partners or the combined clinical trials
with Immunocore’s collaboration partners; statements regarding the
benefits of the Company’s collaboration with Bristol-Meyers Squibb;
and the timing and sufficiency of clinical trial outcomes to
support potential approval of any of the Immunocore’s product
candidates or those of, or combined with, its collaboration
partners. 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, the broader risk of a regional conflict in the Middle
East, 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
inflation, 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 Securities and Exchange
Commission. 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
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