Post-progression outcomes showed significant and sustained
improvement for RYBREVANT® plus standard of care versus
chemotherapy alone
BARCELONA, Sept. 14,
2024 /PRNewswire/ -- Johnson & Johnson
(NYSE:JNJ) today announced updated results from the Phase 3
MARIPOSA-2 study which showed
RYBREVANT® (amivantamab-vmjw) combined with
chemotherapy led to consistent benefit across post-progression
outcomes in adult patients with previously treated non-small cell
lung cancer (NSCLC) with epidermal growth factor receptor
(EGFR) exon 19 deletions (ex19del) or L858R substitution
mutations. The data also reveal a favorable trend toward improved
overall survival (OS) compared to chemotherapy alone. Results were
presented at the European Society of Medical Oncology (ESMO) 2024
Congress.1
"The positive overall survival trend seen in MARIPOSA-2 is
incredibly promising, suggesting that amivantamab combined with
chemotherapy could potentially change the treatment landscape for a
population that has historically faced limited options," said Prof.
Sanjay Popat, FRCP, Ph.D., medical
oncologist at the Royal Marsden Hospital and the Institute of
Cancer Research in the United
Kingdom, and presenting author.* "Building on the strong
progression-free survival data previously reported from this study
and by helping more patients stay on treatment for longer, we are
improving their chances for better outcomes."
At the second interim analysis, with a median follow-up of 18.1
months, 50 percent of patients treated with RYBREVANT®
plus chemotherapy were still alive at the 18-month landmark,
compared to 40 percent of those receiving chemotherapy alone
(median OS, 17.7 vs 15.3 months, respectively; hazard ratio [HR],
0.73; [95 percent confidence interval [CI], 0.54–0.99]; nominal
P=0.039). RYBREVANT® plus chemotherapy showed a
significant improvement in treatment discontinuation rates, with
nearly five times as many patients remaining on therapy at 18
months (22 percent) compared to chemotherapy (4 percent) (median
time to treatment discontinuation [TTD], 10.4 vs 4.5 months,
respectively; HR, 0.42; [95 percent CI, 0.33–0.53]; nominal
P<0.0001). Additionally, patients treated with
RYBREVANT® plus chemotherapy experienced a 27 percent
reduction in the risk of symptomatic progression (median time to
symptomatic progression [TTSP], 16.0 vs 11.8 months; HR, 0.73; [95
percent CI, 0.55–0.96]; nominal P=0.026). The time to
subsequent therapy was significantly prolonged with the
RYBREVANT® combination compared to chemotherapy (median
time to subsequent therapy [TTST], 12.2 vs 6.6 months,
respectively; HR, 0.51; [95 percent CI, 0.39–0.65]; nominal
P<0.0001), which also reduced the risk of second disease
progression or death by 36 percent (medan progression-free survival
[PFS2], 16.0 vs 11.6 months, respectively; HR, 0.64; [95 percent
CI, 0.48–0.85]; nominal P=0.002).1
In the MARIPOSA-2 study, the safety profile of
RYBREVANT® in combination with chemotherapy was
consistent with the established profiles of the individual
treatments. Permanent discontinuation of RYBREVANT® due
to adverse reactions occurred in 11 percent of
patients.2
"We are pleased to see that RYBREVANT plus chemotherapy
continues to show improved survival outcomes after a year and a
half of follow-up, providing real benefits to patients with few
other options," said Joshua Bauml,
M.D., Vice President, Lung Cancer Disease Area Stronghold Leader,
Johnson & Johnson Innovative Medicine. "These results
underscore the potential of this combination regimen to make a
meaningful difference for patients, and we anticipate continued
improvement as we move toward the final analysis."
RYBREVANT® plus chemotherapy
received approval by the European Commision in
August 2024 as a treatment for
patients with previously treated NSCLC with common EGFR
mutations based on the superior efficacy and safety profile
demonstrated in this study.
About the MARIPOSA-2 Study
MARIPOSA-2 (NCT04988295) is a randomized, open-label Phase 3
study evaluating the efficacy and safety of two regimens of
RYBREVANT® (with and without LAZCLUZE™) and
chemotherapy. Patients with locally advanced or metastatic
EGFR ex19del or L858R substitution NSCLC who had disease
progression on or after osimertinib were randomized to treatment
with RYBREVANT® plus chemotherapy, RYBREVANT®
plus chemotherapy with LAZCLUZE™, or chemotherapy alone. The dual
primary endpoint was used to compare the progression-free survival
(PFS) (using RECIST v1.1 guidelines) as assessed by blinded
independent central review (BICR) for each experimental arm to
chemotherapy alone. Secondary endpoints included objective response
as assessed by BICR, OS, duration of response (DoR), time to
subsequent therapy, PFS after first subsequent therapy (PFS2) and
intracranial PFS. All study participants underwent serial brain
imaging to allow for the robust assessment of intracranial
endpoints, and to assess the central nervous system (CNS) activity
of RYBREVANT® with and without LAZCLUZE™. As brain
metastases can lead to significant burden and poor outcomes for
patients, this aspect of the study design provides critical
information in an area of high unmet need. The study enrolled 657
patients with locally advanced or metastatic EGFR ex19del or
L858R substitution NSCLC who had disease progression on or after
osimertinib.3
About RYBREVANT®
RYBREVANT® (amivantamab-vmjw), a fully-human
bispecific antibody targeting EGFR and MET with immune
cell-directing activity, is approved in
the U.S., Europe, and in
other markets around the world as monotherapy for the treatment of
adult patients with locally advanced or metastatic NSCLC with
EGFR exon 20 insertion mutations, as detected by an
FDA-approved test, whose disease has progressed on or after
platinum-based chemotherapy.4
RYBREVANT® is approved in the U.S., Europe and in markets around the world in
combination with chemotherapy (carboplatin and pemetrexed) for the
first-line treatment of adult patients with locally advanced or
metastatic NSCLC with EGFR exon 20 insertion mutations, as
detected by an FDA-approved test.
RYBREVANT® is approved in the U.S. in
combination with LAZCLUZE™ (lazertinib) for the first-line
treatment of adult patients with locally advanced or metastatic
NSCLC with EGFR exon 19 deletions or L858R substitution
mutations, as detected by an FDA-approved test. A marketing
authorization application (MAA) and type II extension of
indication application were submitted to the European
Medicines Agency (EMA) seeking approval of LAZCLUZE™ in combination
with RYBREVANT® based on the MARIPOSA
study.
In November 2023, Johnson &
Johnson submitted a supplemental Biologics License
Application (sBLA) to the U.S. FDA for
RYBREVANT® in combination with chemotherapy for the
treatment of patients with EGFR-mutated NSCLC who progressed
on or after osimertinib based on the MARIPOSA-2 study. This
indication was approved in Europe in August
2024.
In June 2024, Johnson &
Johnson submitted a BLA to the U.S. FDA for the subcutaneous
formulation of RYBREVANT® in combination with LAZCLUZE™
for all currently approved or submitted indications of intravenous
(IV) RYBREVANT® in certain patients with NSCLC. A
submission for the extension of the RYBREVANT® marketing
authorization (line extension) was also submitted to the EMA
seeking approval for this indication.
The NCCN Clinical Practice Guidelines in Oncology (NCCN
Guidelines®) for NSCLC§ prefer
next-generation sequencing–based strategies over polymerase chain
reaction–based approaches for the detection of EGFR exon 20
insertion variants. The NCCN Guidelines include:
- Amivantamab-vmjw (RYBREVANT®) plus lazertinib
(LAZCLUZE™) as a Category 1 recommendation for first-line therapy
in patients with locally advanced or metastatic NSCLC with
EGFR exon 19 deletions or exon 21 L858R
mutations.5 †‡
- Amivantamab-vmjw (RYBREVANT®) plus chemotherapy as a
Category 1 recommendation for patients with locally advanced or
metastatic NCSLC with EGFR exon 19 deletions or exon 21
L858R mutations who experienced disease progression after treatment
with osimertinib.5 †‡
- Amivantamab-vmjw (RYBREVANT®) plus carboplatin and
pemetrexed as a Category 1 recommendation for first-line therapy in
treatment-naive patients with newly diagnosed advanced or
metastatic EGFR exon 20 insertion mutation-positive advanced
NSCLC, or as a Category 2A recommendation for patients that have
progressed on or after platinum-based chemotherapy with or without
immunotherapy and have EGFR exon 20 insertion
mutation-positive advanced NSCLC.5 †‡
- Amivantamab-vmjw (RYBREVANT®) as a Category 2A
recommendation for patients that have progressed on or after
platinum-based chemotherapy with or without an immunotherapy and
have EGFR exon 20 insertion mutation-positive
NSCLC.5 †‡
In addition to the MARIPOSA-2 study,
RYBREVANT® is being studied in multiple clinical
trials, including:
- The Phase 3 MARIPOSA (NCT04487080) study assessing
RYBREVANT® in combination with LAZCLUZE™ versus
osimertinib and versus LAZCLUZE™ alone in the first-line treatment
of patients with locally advanced or metastatic NSCLC with
EGFR ex19del or L858R substitution
mutations.6
- • The Phase 3 PAPILLON (NCT04538664) study assessing
RYBREVANT® in combination with carboplatin-pemetrexed
versus chemotherapy alone in the first-line treatment of patients
with advanced or metastatic NSCLC with EGFR exon 20
insertion mutations.7
- The Phase 3 PALOMA-3 (NCT05388669) study assessing LAZCLUZE™
with subcutaneous amivantamab compared to intravenous amivantamab
in patients with EGFR-mutated advanced or metastatic
NSCLC.8
- The Phase 2 PALOMA-2 (NCT05498428) study assessing subcutaneous
amivantamab in patients with advanced or metastatic solid tumors
including EGFR-mutated NSCLC.9
- The Phase 1 PALOMA (NCT04606381) study assessing the
feasibility of subcutaneous administration of amivantamab based on
safety and pharmacokinetics and to determine a dose, dose regimen
and formulation for amivantamab subcutaneous
delivery.10
- The Phase 1 CHRYSALIS (NCT02609776) study evaluating
RYBREVANT® in patients with advanced
NSCLC.11
- The Phase 1/1b CHRYSALIS-2
(NCT04077463) study evaluating RYBREVANT® in combination
with LAZCLUZE™ and LAZCLUZE™ as a monotherapy in patients with
advanced NSCLC with EGFR mutations.12
- The Phase 1/2 METalmark (NCT05488314) study assessing
RYBREVANT® and capmatinib combination therapy in locally
advanced or metastatic NSCLC.13
- The Phase 1/2 PolyDamas (NCT05908734) study assessing
RYBREVANT® and cetrelimab combination therapy in locally
advanced or metastatic NSCLC.14
- The Phase 2 SKIPPirr study (NCT05663866) exploring how to
decrease the incidence and/or severity of first-dose
infusion-related reactions with RYBREVANT® in
combination with LAZCLUZE™ in relapsed or refractory
EGFR-mutated advanced or metastatic NSCLC.15
- The Phase 1/2 swalloWTail (NCT06532032) study assessing
RYBREVANT® and docetaxel combination therapy in patients
with metastatic NSCLC.16
- The Phase 1b/2 OrigAMI-1
(NCT05379595) study assessing RYBREVANT® monotherapy and
in addition to standard-of-care chemotherapy in patients with
advanced or metastatic colorectal cancer.17
- The Phase 1b/2 OrigAMI-4
(NCT06385080) study assessing RYBREVANT® monotherapy and
in addition to standard-of-care therapeutic agents in patients with
recurrent/metastatic head and neck squamous cell
carcinoma.18
For more information,
visit: https://www.RYBREVANT.com.
About LAZCLUZE™
In 2018, Janssen Biotech, Inc., entered into a license and
collaboration agreement with Yuhan Corporation for the development
of LAZCLUZE™ (marketed as LACLAZA in Korea). LAZCLUZE™ is an oral,
third-generation, brain-penetrant EGFR TKI that targets both
the T790M mutation and activating EGFR mutations while
sparing wild-type EGFR. An analysis of the efficacy and
safety of LAZCLUZE™ from the Phase 3 LASER301 study was published
in The Journal of Clinical Oncology in 2023.
About Non-Small Cell Lung Cancer
Worldwide, lung cancer is one of the most common cancers, with
NSCLC making up 80 to 85 percent of all lung cancer
cases.19,20 The main subtypes of NSCLC are
adenocarcinoma, squamous cell carcinoma, and large cell
carcinoma.21 Among the most common driver mutations
in NSCLC are alterations in EGFR, which is a receptor
tyrosine kinase controlling cell growth and
division.22 EGFR mutations are present in 10
to 15 percent of Western patients with NSCLC with adenocarcinoma
histology and occur in 40 to 50 percent of Asian
patients.19,20,23,24,25,26 EGFR ex19del or
EGFR L858R mutations are the most common EGFR
mutations.27 The five- year survival rate for all
people with advanced NSCLC and EGFR mutations treated with
EGFR tyrosine kinase inhibitors (TKIs) is less than 20
percent.28,29 EGFR exon 20 insertion
mutations are the third most prevalent activating EGFR
mutation.30 Patients with EGFR exon 20
insertion mutations have a real-world five-year overall survival
(OS) of eight percent in the frontline setting, which is worse than
patients with EGFR ex19del or L858R mutations, who have a
real-world five-year OS of 19 percent.31
IMPORTANT SAFETY INFORMATION4,32
WARNINGS AND PRECAUTIONS
Infusion-Related Reactions
RYBREVANT® can cause infusion-related reactions
(IRR); signs and symptoms of IRR include dyspnea, flushing, fever,
chills, nausea, chest discomfort, hypotension, and vomiting. The
median time to IRR onset is approximately 1 hour.
RYBREVANT® with
LAZCLUZE™
RYBREVANT® in combination with
LAZCLUZE™ can cause infusion-related reactions. In MARIPOSA
(n=421), IRRs occurred in 63% of patients treated with
RYBREVANT® in combination with LAZCLUZE™, including
Grade 3 in 5% and Grade 4 in 1% of patients. The incidence of
infusion modifications due to IRR was 54% of patients, and IRRs
leading to dose reduction of RYBREVANT® occurred in 0.7%
of patients. Infusion-related reactions leading to permanent
discontinuation of RYBREVANT® occurred in 4.5% of
patients receiving RYBREVANT® in combination with
LAZCLUZE™.
RYBREVANT® with Carboplatin
and Pemetrexed
In PAPILLON (n=151), infusion-related
reactions occurred in 42% of patients treated with
RYBREVANT® in combination with carboplatin and
pemetrexed, including Grade 3 (1.3%) adverse reactions. The
incidence of infusion modifications due to IRR was 40%, and 0.7% of
patients permanently discontinued RYBREVANT®.
RYBREVANT® as a Single
Agent
In CHRYSALIS (n=302), IRR occurred in 66% of
patients treated with RYBREVANT®. Among patients
receiving treatment on Week 1 Day 1, 65% experienced an IRR, while
the incidence of IRR was 3.4% with the Day 2 infusion, 0.4%
with the Week 2 infusion, and cumulatively 1.1% with
subsequent infusions. Of the reported IRRs, 97% were Grade 1-2,
2.2% were Grade 3, and 0.4% were Grade 4. The median time
to onset was 1 hour (range 0.1 to 18 hours) after start of
infusion. The incidence of infusion modifications due to IRR was
62% and 1.3% of patients permanently discontinued
RYBREVANT® due to IRR.
Premedicate with antihistamines, antipyretics, and
glucocorticoids and infuse RYBREVANT® as recommended.
Administer RYBREVANT® via a peripheral line on
Week 1 and Week 2 to reduce the risk of infusion-related
reactions. Monitor patients for signs and symptoms of infusion
reactions during RYBREVANT® infusion in a setting where
cardiopulmonary resuscitation medication and equipment are
available. Interrupt infusion if IRR is suspected. Reduce the
infusion rate or permanently discontinue RYBREVANT®
based on severity.
Interstitial Lung Disease/Pneumonitis
RYBREVANT® can cause severe and fatal interstitial
lung disease (ILD)/pneumonitis.
RYBREVANT® with
LAZCLUZE™
In MARIPOSA, ILD/pneumonitis occurred in 3.1% of
patients treated with RYBREVANT® in combination with
LAZCLUZE™, including Grade 3 in 1.0% and Grade 4 in 0.2% of
patients. There was one fatal case (0.2%) of ILD/pneumonitis and
2.9% of patients permanently discontinued RYBREVANT® and
LAZCLUZE™ due to ILD/pneumonitis.
RYBREVANT® with Carboplatin
and Pemetrexed
In PAPILLON, Grade 3 ILD/pneumonitis occurred in
2.6% of patients treated with RYBREVANT® in combination
with carboplatin and pemetrexed, all patients required permanent
discontinuation.
RYBREVANT® as a Single
Agent
In CHRYSALIS, ILD/pneumonitis occurred in 3.3%
of patients treated with RYBREVANT®, with 0.7% of
patients experiencing Grade 3 ILD/pneumonitis. Three patients
(1%) discontinued RYBREVANT® due to
ILD/pneumonitis.
Monitor patients for new or worsening symptoms indicative of
ILD/pneumonitis (e.g., dyspnea, cough, fever). For patients
receiving RYBREVANT® in combination with LAZCLUZE™,
immediately withhold both drugs in patients with suspected
ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is
confirmed. For patients receiving RYBREVANT® as a single
agent or in combination with carboplatin and pemetrexed,
immediately withhold RYBREVANT® in patients with
suspected ILD/pneumonitis and permanently discontinue if
ILD/pneumonitis is confirmed.
Venous Thromboembolic (VTE) Events with Concomitant Use of
RYBREVANT® and LAZCLUZE™
RYBREVANT® in combination with LAZCLUZE™ can cause
serious and fatal venous thromboembolic (VTEs) events, including
deep vein thrombosis and pulmonary embolism. The majority of these
events occurred during the first four months of therapy.
In MARIPOSA, VTEs occurred in 36% of patients receiving
RYBREVANT® in combination with LAZCLUZE™, including
Grade 3 in 10% and Grade 4 in 0.5% of patients. On-study VTEs
occurred in 1.2% of patients (n=5) while receiving anticoagulation
therapy. There were two fatal cases of VTE (0.5%), 9% of patients
had VTE leading to dose interruptions of RYBREVANT®, and
7% of patients had VTE leading to dose interruptions of LAZCLUZE™;
1% of patients had VTE leading to dose reductions of
RYBREVANT®, and 0.5% of patients had VTE leading to dose
reductions of LAZCLUZE™; 3.1% of patients had VTE leading to
permanent discontinuation of RYBREVANT®, and 1.9% of
patients had VTE leading to permanent discontinuation of LAZCLUZE™.
The median time to onset of VTEs was 84 days (range: 6 to
777).
Administer prophylactic anticoagulation for the first four
months of treatment. The use of Vitamin K antagonists is not
recommended. Monitor for signs and symptoms of VTE events and treat
as medically appropriate.
Withhold RYBREVANT® and LAZCLUZE™ based on severity.
Once anticoagulant treatment has been initiated, resume
RYBREVANT® and LAZCLUZE™ at the same dose level at the
discretion of the healthcare provider. In the event of VTE
recurrence despite therapeutic anticoagulation, permanently
discontinue RYBREVANT® and continue treatment with
LAZCLUZE™ at the same dose level at the discretion of the
healthcare provider.
Dermatologic Adverse Reactions
RYBREVANT® can cause severe rash including toxic
epidermal necrolysis (TEN), dermatitis acneiform, pruritus, and dry
skin.
RYBREVANT® with
LAZCLUZE™
In MARIPOSA, rash occurred in 86% of patients
treated with RYBREVANT® in combination with LAZCLUZE™,
including Grade 3 in 26% of patients. The median time to onset of
rash was 14 days (range: 1 to 556 days). Rash leading to dose
interruptions occurred in 37% of patients for RYBREVANT®
and 30% for LAZCLUZE™, rash leading to dose reductions occurred in
23% of patients for RYBREVANT® and 19% for LAZCLUZE™,
and rash leading to permanent discontinuation occurred in 5% of
patients for RYBREVANT® and 1.7% for
LAZCLUZE™.
RYBREVANT® with Carboplatin
and Pemetrexed
In PAPILLON, rash occurred in 89% of patients
treated with RYBREVANT® in combination with carboplatin
and pemetrexed, including Grade 3 (19%) adverse reactions. Rash
leading to dose reductions occurred in 19% of patients, and 2%
permanently discontinued RYBREVANT® and 1.3%
discontinued pemetrexed.
RYBREVANT® as a Single
Agent
In CHRYSALIS, rash occurred in 74% of patients
treated with RYBREVANT® as a single agent, including
Grade 3 rash in 3.3% of patients. The median time to onset of
rash was 14 days (range: 1 to 276 days). Rash leading to
dose reduction occurred in 5% of patients, and
RYBREVANT® was permanently discontinued due to rash in
0.7% of patients.
Toxic epidermal necrolysis occurred in one
patient (0.3%) treated with RYBREVANT® as a single
agent.
Instruct patients to limit sun exposure during and for
2 months after treatment with RYBREVANT® or
LAZCLUZE™ in combination with RYBREVANT®. Advise
patients to wear protective clothing and use broad-spectrum UVA/UVB
sunscreen. Alcohol-free (e.g., isopropanol-free, ethanol-free)
emollient cream is recommended for dry skin.
When initiating RYBREVANT® treatment with or without
LAZCLUZE™, administer alcohol-free emollient cream to reduce the
risk of dermatologic adverse reactions. Consider prophylactic
measures (e.g. use of oral antibiotics) to reduce the risk of
dermatologic reactions. If skin reactions develop, start topical
corticosteroids and topical and/or oral antibiotics. For
Grade 3 reactions, add oral steroids and consider dermatologic
consultation. Promptly refer patients presenting with severe rash,
atypical appearance or distribution, or lack of improvement within
2 weeks to a dermatologist. For patients receiving
RYBREVANT® in combination with LAZCLUZE™, withhold, dose
reduce or permanently discontinue both drugs based on severity. For
patients receiving RYBREVANT® as a single agent or in
combination with carboplatin and pemetrexed, withhold, dose reduce
or permanently discontinue RYBREVANT® based on
severity.
Ocular Toxicity
RYBREVANT® can cause ocular toxicity including
keratitis, blepharitis, dry eye symptoms, conjunctival redness,
blurred vision, visual impairment, ocular itching, eye pruritus,
and uveitis.
RYBREVANT® with
LAZCLUZE™
In MARIPOSA, ocular toxicity occurred in 16% of
patients treated with RYBREVANT® in combination with
LAZCLUZE™, including Grade 3 or 4 ocular toxicity in 0.7% of
patients. Withhold, reduce the dose, or permanently discontinue
RYBREVANT® and continue LAZCLUZE™ based on
severity.
RYBREVANT® with Carboplatin
and Pemetrexed
In PAPILLON, ocular toxicity including
blepharitis, dry eye, conjunctival redness, blurred vision, and eye
pruritus occurred in 9%. All events were Grade 1-2.
RYBREVANT® as a Single
Agent
In CHRYSALIS, keratitis occurred in 0.7% and
uveitis occurred in 0.3% of patients treated with
RYBREVANT®. All events were Grade 1-2.
Promptly refer patients with new or worsening eye symptoms to an
ophthalmologist. Withhold, dose reduce or permanently discontinue
RYBREVANT® based on severity.
Embryo-Fetal Toxicity
Based on its mechanism of action and findings from animal
models, RYBREVANT® and LAZCLUZE™ can cause fetal harm
when administered to a pregnant woman. Advise females of
reproductive potential of the potential risk to the
fetus.
Advise female patients of reproductive potential to use
effective contraception during treatment and for 3 months
after the last dose of RYBREVANT®.
Advise females of reproductive potential to use effective
contraception during treatment with LAZCLUZE™ and for 3 weeks after
the last dose. Advise male patients with female partners of
reproductive potential to use effective contraception during
treatment with LAZCLUZE™ and for 3 weeks after the last
dose.
Adverse Reactions
RYBREVANT® with LAZCLUZE™
For the 421 patients in the MARIPOSA clinical trial who received
RYBREVANT® in combination with LAZCLUZE™, the most
common adverse reactions (≥20%) were rash (86%), nail toxicity
(71%), infusion-related reactions (RYBREVANT®, 63%),
musculoskeletal pain (47%), stomatitis (43%), edema (43%), VTE
(36%), paresthesia (35%), fatigue (32%), diarrhea (31%),
constipation (29%), COVID-19 (26%), hemorrhage (25%), dry skin
(25%), decreased appetite (24%), pruritus (24%), nausea (21%), and
ocular toxicity (16%). The most common Grade 3 or 4 laboratory
abnormalities (≥2%) were decreased albumin (8%), decreased sodium
(7%), increased ALT (7%), decreased potassium (5%), decreased
hemoglobin (3.8%), increased AST (3.8%), increased GGT (2.6%), and
increased magnesium (2.6%).
Serious adverse reactions occurred in 49% of patients who
received RYBREVANT® in combination with LAZCLUZE™.
Serious adverse reactions occurring in ≥2% of patients included VTE
(11%), pneumonia (4%), ILD/pneumonitis and rash (2.9% each),
COVID-19 (2.4%), and pleural effusion and infusion-related reaction
(RYBREVANT®) (2.1% each). Fatal adverse reactions
occurred in 7% of patients who received RYBREVANT® in
combination with LAZCLUZE™ due to death not otherwise specified
(1.2%); sepsis and respiratory failure (1% each); pneumonia,
myocardial infarction, and sudden death (0.7% each); cerebral
infarction, pulmonary embolism (PE), and COVID-19 infection (0.5%
each); and ILD/pneumonitis, acute respiratory distress syndrome
(ARDS), and cardiopulmonary arrest (0.2% each).
RYBREVANT® with Carboplatin and
Pemetrexed
For the 151 patients in the PAPILLON clinical trial who received
RYBREVANT® in combination with carboplatin and
pemetrexed, the most common adverse reactions (≥20%) were rash
(90%), nail toxicity (62%), stomatitis (43%), infusion-related
reaction (42%), fatigue (42%), edema (40%), constipation (40%),
decreased appetite (36%), nausea (36%), COVID-19 (24%), diarrhea
(21%), and vomiting (21%). The most common Grade 3 to 4
laboratory abnormalities (≥2%) were decreased albumin (7%),
increased alanine aminotransferase (4%), increased gamma-glutamyl
transferase (4%), decreased sodium (7%), decreased potassium (11%),
decreased magnesium (2%), and decreases in white blood cells (17%),
hemoglobin (11%), neutrophils (36%), platelets (10%), and
lymphocytes (11%).
Serious adverse reactions occurred in 37% of patients who
received RYBREVANT® in combination with carboplatin and
pemetrexed. Serious adverse reactions in ≥2% of patients included
rash, pneumonia, ILD, pulmonary embolism, vomiting, and COVID-19.
Fatal adverse reactions occurred in 7 patients (4.6%) due to
pneumonia, cerebrovascular accident, cardio-respiratory arrest,
COVID-19, sepsis, and death not otherwise specified.
RYBREVANT® as a Single Agent
For the 129 patients in the CHRYSALIS clinical trial who
received RYBREVANT® as a single agent, the most common
adverse reactions (≥20%) were rash (84%), IRR (64%), paronychia
(50%), musculoskeletal pain (47%), dyspnea (37%), nausea (36%),
fatigue (33%), edema (27%), stomatitis (26%), cough (25%),
constipation (23%), and vomiting (22%). The most common
Grade 3 to 4 laboratory abnormalities (≥2%) were decreased
lymphocytes (8%), decreased albumin (8%), decreased phosphate (8%),
decreased potassium (6%), increased alkaline phosphatase (4.8%),
increased glucose (4%), increased gamma-glutamyl transferase (4%),
and decreased sodium (4%).
Serious adverse reactions occurred in 30% of patients who
received RYBREVANT®. Serious adverse reactions in ≥2% of
patients included pulmonary embolism, pneumonitis/ILD, dyspnea,
musculoskeletal pain, pneumonia, and muscular weakness. Fatal
adverse reactions occurred in 2 patients (1.5%) due to pneumonia
and 1 patient (0.8%) due to sudden death.
LAZCLUZE™ Drug Interactions
Avoid concomitant use of LAZCLUZE™ with strong and moderate
CYP3A4 inducers. Consider an alternate concomitant medication with
no potential to induce CYP3A4.
Monitor for adverse reactions associated with a CYP3A4 or BCRP
substrate where minimal concentration changes may lead to serious
adverse reactions, as recommended in the approved product labeling
for the CYP3A4 or BCRP substrate.
Please read full Prescribing
Information for
RYBREVANT®.
Please read full Prescribing
Information for LAZCLUZE™.
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our
strength in healthcare innovation empowers us to build a world
where complex diseases are prevented, treated, and cured, where
treatments are smarter and less invasive, and solutions are
personal. Through our expertise in Innovative Medicine and MedTech,
we are uniquely positioned to innovate across the full spectrum of
healthcare solutions today to deliver the breakthroughs of
tomorrow, and profoundly impact health for humanity. Learn more at
https://www.jnj.com/ or at
www.janssen.com/johnson-johnson-innovative-medicine. Follow us at
@JanssenUS and @JNJInnovMed. Janssen Research &
Development, LLC, and Janssen Biotech, Inc. are Johnson &
Johnson companies.
Cautions Concerning Forward-Looking
Statements
This press release contains "forward-looking statements" as
defined in the Private Securities Litigation Reform Act of 1995
regarding product development and the potential benefits and
treatment impact of RYBREVANT® (amivantamab-vmjw) and
LAZCLUZE™ (lazertinib). The reader is cautioned not to rely on
these forward-looking statements. These statements are based on
current expectations of future events. If underlying assumptions
prove inaccurate or known or unknown risks or uncertainties
materialize, actual results could vary materially from the
expectations and projections of Janssen Research & Development,
LLC, Janssen Biotech, Inc. and/or Johnson & Johnson. Risks and
uncertainties include, but are not limited to: challenges and
uncertainties inherent in product research and development,
including the uncertainty of clinical success and of obtaining
regulatory approvals; uncertainty of commercial success;
manufacturing difficulties and delays; competition, including
technological advances, new products and patents attained by
competitors; challenges to patents; product efficacy or safety
concerns resulting in product recalls or regulatory action; changes
in behavior and spending patterns of purchasers of health care
products and services; changes to applicable laws and regulations,
including global health care reforms; and trends toward health care
cost containment. A further list and descriptions of these risks,
uncertainties and other factors can be found in Johnson &
Johnson's Annual Report on Form 10-K for the fiscal year ended
December 31, 2023, including in the
sections captioned "Cautionary Note Regarding Forward-Looking
Statements" and "Item 1A. Risk Factors," and in Johnson &
Johnson's subsequent Quarterly Reports on Form 10-Q and other
filings with the Securities and Exchange Commission. Copies of
these filings are available online at www.sec.gov, www.jnj.com
or on request from Johnson & Johnson. None of Janssen Research
& Development, LLC, Janssen Biotech, Inc. nor Johnson &
Johnson undertakes to update any forward-looking statement as a
result of new information or future events or developments.
*Prof. Sanjay Popat has provided consulting, advisory, and
speaking services to Johnson & Johnson; he has not been paid
for any media work.
†See the NCCN Guidelines for detailed
recommendations, including other treatment options.
‡The NCCN Guidelines for NSCLC provide
recommendations for certain individual biomarkers that should be
tested and recommend testing techniques but do not endorse any
specific commercially available biomarker assays or commercial
laboratories.
§The NCCN Content does not constitute medical advice
and should not be used in place of seeking professional medical
advice, diagnosis or treatment by licensed practitioners. NCCN
makes no warranties of any kind whatsoever regarding their content,
use or application and disclaims any responsibility for their
application or use in any way.
1 Popat, et al. Overall Survival Among Patients
Receiving Amivantamab Plus Chemotherapy vs Chemotherapy in
EGFR-mutated, Advanced Non-small Cell Lung Cancer After Disease
Progression on Osimertinib (MARIPOSA-2). 2024 European Society for
Medical Oncology. September 14,
2024.
2 Passaro P, et al. Amivantamab Plus Chemotherapy
(With or Without LAZCLUZE™) vs Chemotherapy Alone in EGFR-mutated,
Advanced Non-small Cell Lung Cancer (NSCLC) After Progression on
Osimertinib: MARIPOSA-2, a Phase 3, Global, Randomized, Controlled
Trial. 2023 European Society for Medical Oncology. October 23, 2023.
3 ClinicalTrials.gov. A Study of Amivantamab and
LAZCLUZE™ in Combination With Platinum-Based Chemotherapy Compared
With Platinum-Based Chemotherapy in Patients With Epidermal Growth
Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic
Non-Small Cell Lung Cancer After Osimertinib Failure (MARIPOSA-2).
Available at:
https://classic.clinicaltrials.gov/ct2/show/study/NCT04988295.
Accessed September
2024.
4 RYBREVANT® Prescribing
Information. Horsham, PA: Janssen Biotech, Inc.
5 Referenced with permission from the NCCN Clinical
Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small
Cell Lung Cancer V.9.2024© National Comprehensive Cancer Network,
Inc. All rights reserved. To view the most recent and complete
version of the guideline, go online to NCCN.org. Accessed
September 2024.
6 ClinicalTrials.gov. A Study of Amivantamab and
Lazertinib Combination Therapy Versus Osimertinib in Locally
Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA)
Available at:
https://classic.clinicaltrials.gov/ct2/show/NCT04487080. Accessed
September 2024.
7 ClinicalTrials.gov. A Study of Combination
Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With
Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic
Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor
Receptor (EGFR) Exon 20 Insertions (PAPILLON). Available at:
https://clinicaltrials.gov/ct2/show/NCT04538664. Accessed
September 2024.
8 ClinicalTrials.gov. A Study of LAZCLUZE™ With
Subcutaneous Amivantamab Compared With Intravenous Amivantamab in
Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated
Advanced or Metastatic Non-small Cell Lung Cancer (PALOMA-3).
https://clinicaltrials.gov/ct2/show/NCT05388669. Accessed
September 2024.
9 ClinicalTrials.gov. A Study of Amivantamab in
Participants With Advanced or Metastatic Solid Tumors Including
Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung
Cancer (PALOMA-2). https://clinicaltrials.gov/ct2/show/NCT05498428.
Accessed September 2024.
10 ClinicalTrials.gov. A Study of Amivantamab
Subcutaneous (SC) Administration for the Treatment of Advanced
Solid Malignancies (PALOMA). Available at:
https://clinicaltrials.gov/study/NCT04606381. Accessed September 2024.
11 ClinicalTrials.gov. A Study of Amivantamab, a
Human Bispecific EGFR and cMet Antibody, in Participants With
Advanced Non-Small Cell Lung Cancer (CHRYSALIS).
https://clinicaltrials.gov/ct2/show/NCT02609776. Accessed
September 2024.
12 ClinicalTrials.gov. A Study of LAZCLUZE™ as
Monotherapy or in Combination With Amivantamab in Participants With
Advanced Non-small Cell Lung Cancer (CHRYSALIS-2).
https://clinicaltrials.gov/ct2/show/NCT04077463. Accessed
September 2024.
13 ClinicalTrials.gov. A Study of Amivantamab and
Capmatinib Combination Therapy in Unresectable Metastatic Non-small
Cell Lung Cancer (METalmark).
https://clinicaltrials.gov/ct2/show/NCT05488314. Accessed
September 2024.
14 ClinicalTrials.gov. A Study of Combination
Therapy With Amivantamab and Cetrelimab in Participants With
Metastatic Non-small Cell Lung Cancer (PolyDamas).
https://www.clinicaltrials.gov/study/NCT05908734?term=polydamas&rank=1.
Accessed September 2024.
15 ClinicalTrials.gov. Premedication to Reduce
Amivantamab Associated Infusion Related Reactions (SKIPPirr).
https://classic.clinicaltrials.gov/ct2/show/NCT05663866. Accessed
September 2024.
16 ClinicalTrials.gov. A Study of Combination
Therapy With Amivantamab and Docetaxel in Participants With
Metastatic Non-small Cell Lung Cancer (swalloWTail).
https://www.clinicaltrials.gov/study/NCT06532032?term=Swallowtail&intr=amivantamab&rank=1.
Accessed September 2024.
17 ClinicalTrials.gov. A Study of Amivantamab
Monotherapy and in Addition to Standard-of-Care Chemotherapy in
Participants With Advanced or Metastatic Colorectal Cancer
(OrigAMI-1).
https://clinicaltrials.gov/study/NCT05379595?term=NCT05379595&rank=1.
Accessed September 2024.
18 ClinicalTrials.gov. A Study of Amivantamab Alone
or in Addition to Other Treatment Agents in Participants With
Recurrent/ Metastatic Head and Neck Cancer (OrigAMI-4).
https://clinicaltrials.gov/study/NCT06385080?term=OrigAMI-4&limit=10&rank=1.
Accessed September 2024.
19 The World Health Organization.
Cancer. https://www.who.int/news-room/fact-sheets/detail/cancer.
Accessed September 2024.
20 American Cancer Society. What is Lung
Cancer? https://www.cancer.org/content/cancer/en/cancer/lung-cancer/about/what-is.html.
Accessed September 2024.
21 Oxnard JR, et al. Natural history and
molecular characteristics of lung cancers harboring EGFR exon 20
insertions. J Thorac Oncol. 2013 Feb;8(2):179-84. doi:
10.1097/JTO.0b013e3182779d18.
22 Bauml JM, et al. Underdiagnosis of EGFR Exon 20
Insertion Mutation Variants: Estimates from NGS-based Real World
Datasets. Abstract presented at: World Conference on Lung Cancer
Annual Meeting; January 29, 2021;
Singapore.
23 Pennell NA, et al. A phase II trial of adjuvant
erlotinib in patients with resected epidermal growth factor
receptor-mutant non-small cell lung cancer. J Clin Oncol.
37:97-104.
24 Burnett H, et al. Epidemiological and clinical
burden of EGFR exon 20 insertion in advanced non-small cell lung
cancer: a systematic literature review. Abstract presented at:
World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore.
25 Zhang YL, et al. The prevalence of EGFR mutation in
patients with non-small cell lung cancer: a systematic review and
meta-analysis. Oncotarget. 2016;7(48):78985-78993.
26 Midha A, et al. EGFR mutation incidence in
non-small-cell lung cancer of adenocarcinoma histology: a
systematic review and global map by ethnicity. Am J Cancer Res.
2015;5(9):2892-2911.
27 American Lung Association. EGFR and Lung
Cancer. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/egfr.
Accessed September 2024.
28 Howlader N, et al. SEER Cancer Statistics
Review, 1975-2016, National Cancer Institute. Bethesda, MD,
https://seer.cancer.gov/csr/1975_2016/, based on November 2018 SEER data submission, posted to the
SEER web site.
29 Lin JJ, et al. Five-Year Survival in EGFR-Mutant
Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. J Thorac
Oncol. 2016 Apr;11(4):556-65.
30 Arcila, M. et al. EGFR exon 20 insertion
mutations in lung adenocarcinomas: prevalence, molecular
heterogeneity, and clinicopathologic characteristics. Mol
Cancer Ther. 2013 Feb; 12(2):220-9.
31 Girard N, et al. Comparative clinical outcomes
for patients with NSCLC harboring EGFR exon 20 insertion mutations
and common EGFR mutations. Abstract presented at: World Conference
on Lung Cancer Annual Meeting; January 29,
2021; Singapore.
32 LAZCLUZE™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
Media contact:
Suzanne Frost
sfrost@its.jnj.com
Sarah Freeman
sfreem21@its.jnj.com
|
Investor contact:
Raychel Kruper
investor-relations@its.jnj.com
U.S. Medical Inquiries
+1 800 526-7736
|
View original content to download
multimedia:https://www.prnewswire.com/news-releases/rybrevant-amivantamab-vmjw-plus-chemotherapy-shows-positive-overall-survival-trend-versus-chemotherapy-in-patients-with-previously-treated-egfr-mutated-lung-cancer-302248157.html
SOURCE Johnson & Johnson