- New safety and efficacy data in heavily pre-treated patients
with metastatic colorectal cancer (CRC), from a Phase 1 study of
ABBV-400, a next-generation, potential best-in-class c-Met directed
ADC.
- Data from a first-in-human study of ABBV-706, a potential
best-in-class SEZ6 directed ADC, in small cell lung cancer
(SCLC), high-grade central nervous system (CNS) tumors and
high-grade neuroendocrine neoplasms (NENs).
- Data from the primary analysis of the Phase 2 LUMINOSITY
trial evaluating Telisotuzumab vedotin (Teliso-V), a potential
first-in-class c-Met directed ADC, in advanced non-small cell lung
cancer (NSCLC).
NORTH
CHICAGO, Ill., May 28, 2024
/PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that new data
from its innovative antibody-drug conjugate (ADC) platform will be
showcased across three oral presentations at the upcoming American
Society of Clinical Oncology (ASCO) Annual Meeting (May 31 - June 4, 2024). AbbVie's ADCs are
designed to target unique protein biomarkers such as c-Met (MET
protein) and SEZ6 (seizure-related homolog 6 protein), which are
over-expressed across various tumor types. By utilizing these
biomarkers as targets, ADCs are designed to deliver potent cancer
cell death-inducing agents called 'payloads' to the tumor.
"Building upon our strong commitment to patients and existing
leadership in hematological malignancies, we are rapidly advancing
a differentiated pipeline in solid tumors," said Daejin Abidoye, M.D., vice president, head of
solid tumors, oncology development, AbbVie. "Our ADC platform
allows us to utilize selected biomarkers such as c-Met and SEZ6 to
induce targeted cancer cell death by delivering potent anti-cancer
agents. The data we are presenting at ASCO demonstrate the clinical
potential of this approach across a wide range of
difficult-to-treat tumors."
Data from the dose-escalation and colorectal cancer (CRC)
dose-expansion cohort of an ongoing first-in-human Phase 1 study
(NCT05029882) of ABBV-400, a potential best-in-class c-Met directed
ADC, will be presented in an oral presentation. The preliminary
data show that among 122 heavily pre-treated advanced CRC patients,
promising antitumor activity was observed at 2.4 and 3.0 mg/kg
doses administered once every 3 weeks, with confirmed objective
response rate (ORR) of 18% (n=40) and 24% (n=41) respectively in
those groups. In patients with higher c-Met expression, ORR was
enriched to >35% at doses ≥2.4 mg/kg. The most common Gr≥3
treatment-emergent adverse events (TEAEs) were anemia (35%),
neutropenia (7%) and febrile neutropenia (6%). TEAEs leading to
discontinuation occurred in 25 (20.5%) patients. Additional data
will be presented at the meeting.
ABBV-400 is also being evaluated in a Phase 1b basket study (NCT06084481) in advanced solid
tumors as a monotherapy and a Phase 2 study (NCT06107413) in second
line metastatic CRC in combination with fluorouracil, folinic acid,
and bevacizumab.
"c-Met overexpression, found in the majority of patients with
metastatic CRC, has been reported to be associated with poor
prognosis. However, there are no approved therapies specific for
c-Met–overexpressing CRCs, making it an attractive cancer biomarker
to target," said Manish Sharma,
M.D., Co-Director of Clinical Research at START Midwest
(Grand Rapids, MI) and Principal
Investigator on the ABBV-400 trial. "Results from this Phase 1
study show preliminary evidence of efficacy for ABBV-400 in
patients with heavily pre-treated colorectal cancer and are
supportive of further exploration of this novel ADC in CRC and
other solid tumors".
In addition, early data from the monotherapy dose escalation
part of a first-in-human study of ABBV-706, a potential
best-in-class SEZ6 directed ADC, will be presented at an oral
presentation. The data demonstrate that among a total of 48
efficacy-evaluable patients (23 SCLC and 25 NEN), the overall
confirmed objective response rate was 43.8%. Within the SCLC group,
the confirmed objective response rate was 60.9%. Among all the 53
enrolled patients at the time of data cut-off, the most common ≥3
TEAEs were neutropenia (42%), anemia (42%), and leukopenia (28%).
The ongoing study (NCT05599984) is evaluating ABBV-706 as
monotherapy or in combination with budigalimab (a programmed cell
death 1 inhibitor), carboplatin, or cisplatin, in patients with
advanced solid tumors, including SCLC and other NENs. Additional
data will be presented at the meeting.
Both ABBV-400 and ABBV-706 utilize a novel, AbbVie proprietary
topoisomerase 1 inhibitor (Top1i) payload. Top1i is an anticancer
agent that induces cell death by interrupting DNA replication.
ABBV-400 and ABBV-706 are designed to specifically deliver Top1i to
cells expressing c-Met and SEZ6 respectively.
AbbVie will also present data from the primary analysis of the
Phase 2 LUMINOSITY non-small cell lung cancer (NSCLC) trial
evaluating telisotuzumab vedotin (Teliso-V), a potential
first-in-class c-Met directed ADC utilizing a microtubule
polymerization inhibitor, monomethyl auristatin E (MMAE) payload,
in patients with previously treated c-Met-overexpressing,
non-squamous, epidermal growth factor receptor (EGFR) wild type,
advanced NSCLC. AbbVie previously announced positive topline
results from the study in November
2023.
Other presentations from AbbVie's ADC platform include safety
and efficacy data in an older population (≥ 65) from the Phase 3
MIRASOL trial of mirvetuximab soravtansine (MIRV) vs investigator's
choice chemotherapy in patients with platinum-resistant ovarian
cancer (PROC) and high folate receptor-alpha (FRα) expression, and
a retrospective, exploratory pooled analysis characterizing
long-term survivors from four clinical trials examining patients
with folate receptor alpha-positive recurrent ovarian cancer
treated with MIRV monotherapy.
Further information on AbbVie clinical trials is available
at https://www.clinicaltrials.gov/.
Additional details on oral presentations at ASCO are available
below:
Title
|
Date/Time
|
Session
|
Abstract
number
|
First-in-human study of
ABBV-706, a
seizure-related homolog protein 6
(SEZ6)–targeting antibody-drug
conjugate (ADC), in patients (pts) with
advanced solid tumors.
|
1 June,
3:12 PM
CDT
|
Developmental
Therapeutics—
Molecularly Targeted
Agents and Tumor
Biology
Oral Abstract Session
|
Abstract:
3001
|
Telisotuzumab vedotin
monotherapy in
patients with previously treated c-Met–
overexpressing non-
squamous EGFR wildtype advanced
NSCLC: Primary analysis of the
LUMINOSITY trial.
|
2 June,
10:01 AM CDT
|
Next-Generation
Antibody–Drug
Conjugates: The
Revolution Continues
Clinical Science
Symposium
|
Abstract: 103
|
First-in-human study of
ABBV-400, a
novel c-Met–targeting antibody-drug
conjugate, in advanced solid tumors:
Results in colorectal cancer.
|
3 June,
2:15 PM
CDT
|
Gastrointestinal
Cancer—Colorectal and
Anal
Rapid Oral
Abstract
Session
|
Abstract:
3515
|
ABOUT ELAHERE® (mirvetuximab
soravtansine-gynx)
ELAHERE is a first-in-class ADC comprising a folate receptor
alpha-binding antibody, cleavable linker, and the maytansinoid
payload DM4, a potent tubulin inhibitor designed to kill the
targeted cancer cells. Patients requiring access support may call
1-833-ELAHERE or visit www.elahere.com.
The Marketing Authorization Application (MAA) for ELAHERE
in Europe has been accepted by the European
Medicines Agency (EMA). Regulatory submissions for ELAHERE are
also under review in multiple other countries.
INDICATION
ELAHERE is indicated for the treatment of
adult patients with folate receptor-alpha (FRα) positive,
platinum-resistant epithelial ovarian, fallopian tube, or primary
peritoneal cancer, who have received one to three prior systemic
treatment regimens. Select patients for therapy based on an
FDA-approved test.
IMPORTANT SAFETY INFORMATION
WARNING: OCULAR TOXICITY
- ELAHERE can cause severe ocular toxicities, including visual
impairment, keratopathy, dry eye, photophobia, eye pain, and
uveitis.
- Conduct an ophthalmic exam including visual acuity and slit
lamp exam prior to initiation of ELAHERE, every other cycle for the
first 8 cycles, and as clinically indicated.
- Administer prophylactic artificial tears and ophthalmic topical
steroids.
- Withhold ELAHERE for ocular toxicities until improvement and
resume at the same or reduced dose.
- Discontinue ELAHERE for Grade 4 ocular toxicities.
WARNINGS and PRECAUTIONS
Ocular Disorders
ELAHERE can cause severe ocular adverse reactions, including
visual impairment, keratopathy (corneal disorders), dry eye,
photophobia, eye pain, and uveitis.
Ocular adverse reactions occurred in 59% of patients with
ovarian cancer treated with ELAHERE. Eleven percent (11%) of
patients experienced Grade 3 ocular adverse reactions, including
blurred vision, keratopathy (corneal disorders), dry eye, cataract,
photophobia, and eye pain; two patients (0.3%) experienced Grade 4
events (keratopathy and cataract). The most common (≥5%) ocular
adverse reactions were blurred vision (48%), keratopathy (36%), dry
eye (27%), cataract (16%), photophobia (14%), and eye pain
(10%).
The median time to onset for first ocular adverse reaction was
5.1 weeks (range: 0.1 to 68.6). Of the patients who experienced
ocular events, 53% had complete resolution; 38% had partial
improvement (defined as a decrease in severity by one or more
grades from the worst grade at last follow up). Ocular adverse
reactions led to permanent discontinuation of ELAHERE in 1% of
patients.
Premedication and use of lubricating and ophthalmic topical
steroid eye drops during treatment with ELAHERE are recommended.
Advise patients to avoid use of contact lenses during treatment
with ELAHERE unless directed by a healthcare provider.
Refer patients to an eye care professional for an ophthalmic
exam including visual acuity and slit lamp exam prior to treatment
initiation, every other cycle for the first 8 cycles, and as
clinically indicated. Promptly refer patients to an eye care
professional for any new or worsening ocular signs and
symptoms.
Monitor for ocular toxicity and withhold, reduce, or permanently
discontinue ELAHERE based on severity and persistence of ocular
adverse reactions.
Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease
(ILD), including pneumonitis, can occur in patients treated with
ELAHERE.
Pneumonitis occurred in 10% of patients treated with ELAHERE,
including 1% with Grade 3 events and 1 patient (0.1%) with a Grade
4 event. One patient (0.1%) died due to respiratory failure in the
setting of pneumonitis and lung metastases. One patient (0.1%) died
due to respiratory failure of unknown etiology. Pneumonitis led to
permanent discontinuation of ELAHERE in 3% of patients.
Monitor patients for pulmonary signs and symptoms of
pneumonitis, which may include hypoxia, cough, dyspnea, or
interstitial infiltrates on radiologic exams. Infectious,
neoplastic, and other causes for such symptoms should be excluded
through appropriate investigations. Withhold ELAHERE for patients
who develop persistent or recurrent Grade 2 pneumonitis until
symptoms resolve to ≤ Grade 1 and consider dose reduction.
Permanently discontinue ELAHERE in all patients with Grade 3 or 4
pneumonitis. Patients who are asymptomatic may continue dosing of
ELAHERE with close monitoring.
Peripheral Neuropathy (PN)
Peripheral neuropathy occurred in 36% of patients with ovarian
cancer treated with ELAHERE across clinical trials; 3% of patients
experienced Grade 3 peripheral neuropathy. Peripheral neuropathy
adverse reactions included peripheral neuropathy (20%), peripheral
sensory neuropathy (9%), paraesthesia (6%), neurotoxicity (3%),
hypoaesthesia (1%), peripheral motor neuropathy (0.9%),
polyneuropathy (0.3%), and peripheral sensorimotor neuropathy
(0.1%). Monitor patients for signs and symptoms of neuropathy, such
as paresthesia, tingling or a burning sensation, neuropathic pain,
muscle weakness, or dysesthesia. For patients experiencing
new or worsening PN, withhold dosage, dose reduce, or permanently
discontinue ELAHERE based on the severity of PN.
Embryo-Fetal Toxicity
Based on its mechanism of action, ELAHERE can cause embryo-fetal
harm when administered to a pregnant woman because it contains a
genotoxic compound (DM4) and affects actively dividing cells.
Advise pregnant women of the potential risk to a fetus. Advise
females of reproductive potential to use effective contraception
during treatment with ELAHERE and for 7 months after the last
dose.
ADVERSE REACTIONS
The most common (≥20 %) adverse reactions, including lab
abnormalities, were increased aspartate aminotransferase, fatigue,
increased alanine aminotransferase, blurred vision, nausea,
increased alkaline phosphatase, diarrhea, abdominal pain,
keratopathy, peripheral neuropathy, musculoskeletal pain, decreased
lymphocytes, decreased platelets, decreased magnesium, decreased
hemoglobin, dry eye, constipation, decreased leukocytes, vomiting,
decreased albumin, decreased appetite, and decreased
neutrophils.
DRUG INTERACTIONS
DM4 is a CYP3A4 substrate. Closely monitor patients for adverse
reactions with ELAHERE when used concomitantly with strong CYP3A4
inhibitors.
USE IN SPECIAL POPULATIONS
Lactation
Advise women not to breastfeed during
treatment with ELAHERE and for 1 month after the last dose.
Hepatic Impairment
Avoid use of ELAHERE in patients
with moderate or severe hepatic impairment (total bilirubin >1.5
ULN).
Please see full Prescribing Information, including BOXED
WARNING
About AbbVie in Oncology
At AbbVie, we are
committed to transforming standards of care for patients living
with difficult-to-treat cancers. We are advancing a dynamic
pipeline of investigational therapies across a range of cancer
types in both blood cancers and solid tumors. We are focusing on
creating targeted medicines that either impede the reproduction of
cancer cells or enable their elimination. We achieve this through
various, targeted treatment modalities including Antibody Drug
Conjugates (ADCs), Immuno-Oncology, bi-specific antibody and CAR-T
platforms. Our dedicated and experienced team joins forces
with innovative partners to accelerate the delivery of potential
breakthrough medicines.
Today, our expansive oncology portfolio comprises of approved
and investigational treatments for a wide range of blood and solid
tumors. We are evaluating more than 20 investigational medicines in
multiple clinical trials across some of the world's most widespread
and debilitating cancers. As we work to have a remarkable impact on
people's lives, we are committed to exploring solutions to help
patients obtain access to our cancer medicines. For more
information, please visit http://www.abbvie.com/oncology.
About AbbVie
AbbVie's mission is to discover and
deliver innovative medicines and solutions that solve serious
health issues today and address the medical challenges of tomorrow.
We strive to have a remarkable impact on people's lives across
several key therapeutic areas – immunology, oncology, neuroscience,
and eye care – and products and services in our Allergan Aesthetics
portfolio. For more information about AbbVie, please visit us at
www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X
(formerly Twitter), and YouTube.
Forward-Looking Statements
Some statements in this
news release are, or may be considered, forward-looking statements
for purposes of the Private Securities Litigation Reform Act of
1995. The words "believe," "expect," "anticipate," "project" and
similar expressions and uses of future or conditional verbs,
generally identify forward-looking statements. AbbVie cautions that
these forward-looking statements are subject to risks and
uncertainties that may cause actual results to differ materially
from those expressed or implied in the forward-looking statements.
Such risks and uncertainties include, but are not limited to,
challenges to intellectual property, competition from other
products, difficulties inherent in the research and development
process, adverse litigation or government action, and changes to
laws and regulations applicable to our industry. Additional
information about the economic, competitive, governmental,
technological and other factors that may affect AbbVie's operations
is set forth in Item 1A, "Risk Factors," of AbbVie's 2022 Annual
Report on Form 10-K, which has been filed with the Securities and
Exchange Commission, as updated by its subsequent Quarterly Reports
on Form 10-Q. AbbVie undertakes no obligation, and specifically
declines, to release publicly any revisions to forward-looking
statements as a result of subsequent events or developments, except
as required by law.
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