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2022 Milestone Clinical Study TOP10

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Let the years go by, the world will be vicissitudes, and 2022 will finally be a thing of the past
.
This year has been a year where we have experienced many difficulties, but we have also ushered in some key results of some blockbuster clinical studies, including new breakthroughs that reshape clinical treatment, breakthroughs in innovative therapies, or key studies
that support the launch of drugs.
Here, the Med team once again selects the "milestone" clinical research results disclosed in 2022 to support the launch of transformative therapies for your reference
.

NO.
1 DOVALUMAB TOPAZ-1

Research company: AstraZeneca

Clinical significance: The first biliary tract cancer immunotherapy, a new standard of first-line treatment

In January 2022, at the 2022 American Society of Clinical Oncology Gastrointestinal Cancer Symposium (ASCO).
GI) published data from the Phase III study (TOPAZ-1) of davalumab in combination with chemotherapy in patients with advanced biliary system tumors who have not been systematically treated
.
The results showed that the risk of death was 20%
lower in the durvalumab plus chemotherapy group compared with chemotherapy alone.
At 18 months follow-up, overall survival was 35.
1% in the durvalumab combination group compared with 25.
6%
in the chemotherapy alone group.
At follow-up to 2 years, the overall survival rates of the two groups were 24.
9% and 10.
4%,
respectively.

Specifically, progression-free survival and overall survival were significantly improved in the durvalumab combination group compared with placebo, at 7.
2 versus 5.
7 months (HR, 0.
75; 95% CI).
0.
63-0.
89; P = 0.
001), the median OS of the two groups was 12.
8 months and 11.
5 months
, respectively.
Immunotherapy also improved the objective response rate (ORR), ORR in both groups 26.
7% and 18.
7%, respectively; However, the disease control rates were similar in the two groups, 85.
3% and 82.
6%, respectively; The median duration to response was similar, at 6.
4 months and 6.
2 months
, respectively.

In September 2022, the FDA was the first to approve durvalumab in combination with chemotherapy for the first-line treatment
of cholangiocarcinoma, based on the results of the TOPAZ-1 study.
However, even if it is recognized by regulatory agencies and included in clinical guidelines, durvalumab combined with chemotherapy still faces many problems and challenges
in cholangiocarcinoma.
A hepatobiliary surgeon in a tertiary hospital in China believes that although the TOPAZ-1 study is sufficient to change the guidelines, it has become the standard first-line treatment
for advanced biliary system tumors.
However, efficacy data were somewhat unsatisfactory, with a median OS extension of only 1.
3 months
.
Although patient benefit increases further over time; But if you look closely at the survival curve, the difference between the two groups slowly appears
after 6 months.

In addition, there are some differences
in the design of the TOPAZ-1 study from clinical practice.
In this study, the control group stopped the drug directly after 8 cycles of GC chemotherapy, which is not completely consistent
with clinical practice.

NO.
2 Nivolumab CheckMate-816

Research company: Bristol-Myers Squibb

Clinical significance: The first immunoneoadjuvant therapy for lung cancer

CheckMate-816 is the first phase III clinical study
to demonstrate that immune-based combination therapy can significantly improve EFS and pathologically complete response (pCR) rates in patients with non-small cell lung cancer during the neoadjuvant phase.
In April 2022, EFS data from the CheckMate-816 study were first presented at the American Association for Cancer Research (AACR) annual meeting and simultaneously published in the New England Journal of Medicine
.

CheckMate-816 was a randomized, open-label, multicenter phase III clinical trial designed to evaluate the efficacy of nivolumab (nivolumab) in combination with chemotherapy as neoadjuvant therapy compared with chemotherapy alone in patients with resectable stage IB to IIIA NSCLC, with the primary endpoints being EFS (event-free survival) and pCR (pathologically complete response rate).

。 In the main analysis, 358 patients were randomized to nivolumab (360 mg) in combination with platinum-double-agent chemotherapy based on histologic classification (every 3 weeks, up to 3 cycles) or platinum-duplex chemotherapy alone (every 3 weeks, up to 3 cycles).

The first published EFS data showed that patients who received nivolumab in combination with chemotherapy before surgery had a 37% lower risk of disease recurrence, progression, or death (HR 0.
63, p=0.
0052), median EFS was 31.
6 months in the nivolumab combination chemotherapy group and 20.
8 months
in the platinum-doublet chemotherapy group alone.

In March 2022, the FDA approved nivolumab in combination with chemotherapy for resectable (tumor≥4 cm or node-positive) non-small cell lung cancer (NSCLC) Neoadjuvant therapy
in adult patients.
Nivolumab is the first neoadjuvant immunotherapy in the field of lung cancer, and the only immunoneoadjuvant therapy in lung cancer so far, which has enabled immunotherapy to complete the full-line treatment qualification layout of neoadjuvant, adjuvant, first-line and above multi-course treatment in the field of lung cancer
.

NO.
3 DTROSTUZUMAB DESTINY-BREAST04

Research company: AstraZeneca/Daiichi Sankyo

Clinical significance: The first HER2 low-expression targeted therapy

Shanu from Memorial Sloan Kettering Cancer Center, June 2022 Dr.
Modi presented the high-profile latest data
from DESTINY-Breast04 at the American Society of Clinical Oncology (ASCO) meeting.
The DESTINY-Breast04 study is the first randomized Phase III clinical trial
in patients with metastatic breast cancer with low HER2 expression.
Patients with HER2 hypoexpressive, unresectable, and/or metastatic breast cancer who had previously received 1~2 lines of chemotherapy in metastatic state were included; HR+ patients were endocrine refractory patients who were randomly divided into dtrostuzumab (Enhertu, T-DXd) group and physician-selected treatment (TPC) group according to 2:1 randomization
.
The primary endpoint was PFS (HR+) for BICR (blinded independent center assessment); Secondary endpoints included: PFS (all patients), OS (HR+ patients, all patients)
for BICR.

The results showed that the PFS of the T-DXd group and the TPC group were 10.
1 months and 5.
4 months (HR=0.
51, P<0.
0001), respectively, and the PFS of the T-DXd group and TPC group were 9.
9 months and 5.
1 months (HR=0.
50, P<0.
0001),<b10> respectively 。 In terms of OS, the OS of the T-DXd group and the TPC group were 23.
9 months and 17.
5 months, respectively (HR=0.
64, P=0.
0028).
In the total population, the OS of the T-DXd group and the TPC group were 23.
4 months and 16.
8 months, respectively (HR=0.
64, P=0.
0010).

In addition, in the HR-population, PFS in the T-DXd group and TPC group was 8.
5 months and 2.
9 months, respectively (HR=0.
46); The OS of the T-DXd group and the TPC group were 18.
2 months and 8.
3 months, respectively (HR=0.
48).

At the same time, ORR data also has significant advantages
for both HR+ and HR- people.
Overall, the DESTINY-Breast04 study met the primary and secondary endpoints, benefiting all subgroups
.
It was the success of the DESTINY-Breast04 study that detrostuzumab was approved by the FDA in August 2022 for the treatment of unresectable or metastatic properties Adult patients
with HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer.

The success of the DESTINY-Breast04 study led to the first HER2-low expression breast cancer therapy and challenged
breast cancer treatment patterns and classifications as well as markers.
Of course, it is also possible that the HER2 expression level required for T-DXd to exert therapeutic activity is lower than the current detection sensitivity of IHC, and there are new requirements
on how to assess HER2 status in a more accurate and sensitive way.
However, with the DAISY study, T-DXd was negative for HER2 (IHC 0) Patients also have an objective response rate (ORR) performance of nearly 30%, which may also cause a rethinking
of the ADC drug concept.

In addition, drestrolizumab was also approved in August 2022 for treatment advanced NSCLC carrying HER2-activating mutations based on DESTINY-Lung01 research, becoming the only approved treatment for HER2 targets in the field of lung cancer so far, filling the drug gap
of HER2-mutant NSCLC.

NO.
4 KarXT for the treatment of schizophrenia EMERGENT-2

Research company: Karuna Therapeutics

Clinical significance: The first new drug for schizophrenia in 50 years is expected to be available

August 2022, Karuna Therapeutics announced that its drug KarXT (xanomeline-trospium) for the treatment of schizophrenia in adults has achieved its primary endpoint
in the Phase III EMERGENT-2 trial.
Karuna plans to submit a New Drug Application (NDA) to the FDA in mid-2023, making it potentially the first new class of drugs
to treat schizophrenia in 50 years.

KarXT (xanomeline-trospium) is an oral M1/M4 muscarinic agonist, consisting of muscarinic agonists Xanomeline and the muscarinic antagonist trospium, designed to preferentially stimulate muscarinic receptors in the central nervous system, relieve negative symptoms such as apathy, reduced social drive, improve cognitive abilities, and be helpful
in improving other psychiatric symptoms such as hallucinations and delusions.
Quaternary ammonium compound trospium Chloride is a muscarinic receptor antagonist that inhibits the side effects
of xanomeline in peripheral nerves.
KarXT is under development for the treatment of psychiatric and neurological disorders, including schizophrenia and psychosis in Alzheimer's disease, and has the potential to become the first novel drug
with dual mechanisms that do not target dopaminergic and serotonergic pathways.

The EMERGENT-2 trial is a double-blind, placebo-controlled, five-week Phase III clinical study evaluating the efficacy, safety, and tolerability status of KarXT compared with placebo in adult schizophrenia patients in the United States
.
The primary endpoint was KarXT positive and negative symptom scale compared to placebo at week 5 (PANSS) The change in the total score (a scale that measures the severity of schizophrenic symptoms) from baseline
.
Results showed that after 5 weeks, the total score of the positive and negative symptom scale in the KarXT group was significantly reduced by 9.
6 points compared to baseline (p<0.
0001)
compared to placebo.
The study also met key secondary endpoints, indicating a basis As measured by the PANSS-positive, PANSS-negative, and PANSS-negative Marder factor scales, both positive and negative symptoms of schizophrenia were statistically significantly reduced
.

Steve, Chief Executive Officer, President and Chairman of Karuna Therapeutics Paul M.
D.
noted that the EMERGENT-2 study is the second positive registration trial result for KarXT to support the plan to submit a new drug application for KarXT for schizophrenia to the FDA in mid-2023, reinforcing KarXT's new, unique mechanism and potentially bringing the first drug with a novel mechanism of action in more than 50 years for patients with schizophrenia
.

NO.
5 Aprocitentan for the treatment of refractory hypertension

Research company: Idorsia/Actelion Pharma

Clinical significance: It is expected to create the first innovative hypertension drug in 30 years

In May 2022, Idosia announced the positive first-line results
of the PRECISION study.
PRECISION IS A STUDY Idorsia's dual endothelin receptor antagonist, aprocitentan, was used to treat patients
who received at least triple antihypertensive therapy but whose blood pressure was still not adequately controlled (known as intractable hypertension).

Worldwide, there are about 1.
3 billion people with hypertension, and 10% of them, or more than 100 million patients, have refractory hypertension, that is, their blood pressure remains uncontrolled
despite receiving at least 3 different types of antihypertensive drugs.
The endothelin pathway is associated with the pathogenesis of hypertension, endothelin-1 (ET-1) is a potent vasoconstrictor that also induces neurohormonal activation, vasohypertrophy and remodeling, cardiac hypertrophy and fibrosis, and endothelial dysfunction
.
In hypertension, both ETA and ETB receptors mediate ET-1 of harmful effects
.

Aprocitentan, as a novel oral dual endothelin receptor antagonist, is the active metabolite of masitetan with a longer half-life (48 vs 14 hours) and a higher accumulation index, which effectively suppresses ET-1 with ETA and ETB Binding
of receptors.
The PRECISION trial was a multicentre, blinded, randomised, parallel-group controlled phase III study conducted in hospitals or research centres in Europe, North America, Asia and Australia
.
The included patients received standardized background therapy consisting of three antihypertensive drugs, including diuretics, but the systolic blood pressure remained at 140 mm Hg or higher
.
The study consists of three consecutive parts: Part 1 is a period of 4 Weeks of double-blind, randomized, and placebo-controlled portions, in which 730 patients were randomized 1:1:1 to aprocitentan 12.
5 mg (n=243), 25 mg (n=243), or placebo (n=244)； 2 The portion was a single (patient) blinded portion for 32 weeks, in which all patients were treated with 25 mg of aprocitentan (n=704); Part 3 is a 12-week double-blind, randomized, placebo-controlled discontinuation portion in which patients are given The 1:1 ratio was randomly assigned to aprocitentan 25 mg (n=307) or placebo (n=307).

The primary and critical secondary endpoints were change in systolic blood pressure from baseline to week 4 and from baseline to week 40 in unattended offices, respectively, and secondary endpoints included change in 24-hour ambulatory blood pressure
.

The results showed that Aprocitentan was in the 4th place of treatment compared to placebo Weeks lowered blood pressure, the effect was maintained and confirmed over 48 weeks, and was generally well tolerated
.
Specifically, at 4 weeks aprocitentan Office systolic blood pressure in the 12.
5 mg, 25 mg, and placebo groups decreased by 15.
3 mmHg, 15.
2 mmHg, and 11.
5, respectively, from baseline mmHg； Compared with placebo, apricitantan 12.
5 mg and 25 mg had a significant reduction in systolic blood pressure of 3.
8 mmHg (95% CI: -6.
8~-0.
8;P=0.
0042) and 3.
7 mmHg (95%CI: -6.
7~-0.
8; P=0.
0046); the 24-hour dynamic systolic blood pressure decreased by 4.
2, respectively mmHg (95% CI: -6.
2~-2.
1) and 5.
9 mmHg (95%CI: -7.
9~-3.
8).

After 4 weeks of discontinuation of the drug, the systolic blood pressure in the clinic was significantly increased in the placebo group (5.
8 mmHg，95%CI: 3.
7-7.
9，P＜0.
0001）
。 Overall, both the primary and critical secondary endpoints of the study achieved statistically significant and clinically significant results

In November 2022, the full results of the PRECISION study were published in The Lancet and published in the 2022 American Heart Association (AHA) Presented
as the latest breakthrough scientific report at the scientific conference.
In December, Idosia announced the completion of a New Drug Application (NDA) for aprocitentan to the FDA for the treatment of patients
with refractory hypertension.
According to the press release, if the drug is finally approved, it could become the first blood pressure-lowering drug
based on a new mechanism in 30 years.

NO.
6 AXS-05 FOR THE TREATMENT OF Alzheimer's disease agitated accord

Research company: Axsome

Clinical significance: It is expected to promote the first Alzheimer's disease agitator drug to market

In November 2022, Axsome announced the AXS-05 (dextromethorphan + Key data
from ACCORD (NCT04797715) in the phase III clinical trial of bupropion) for the treatment of Alzheimer's disease.
ACCORD is a phase III, randomized, double-blind, placebo-controlled, multicenter trial of 178 patients
diagnosed with suspected Alzheimer's disease and clinically significant agitation associated with other conditions.
Participants were first treated with AXS-05 in an open-label format for 9 weeks, and 108 patients who demonstrated sustained clinical response then entered a double-blind phase in a 1:1 ratio and received either AXS-05 (n=53) or placebo (n=55) until agitation recurred or treatment was completed 26 The test
is stopped after a week.
Sustained clinical response is defined as a ≥30% improvement in Cohen-Mansfield Agitation Scale (CMAI) scores and a PGI-C (score ≤3) sustained for at least 4 consecutive weeks
.
Agitation recurrence is defined as deterioration of the total CMAI score ≥ 10 points after randomization or a total CMAI score above baseline; or hospitalization
due to agitation associated with Alzheimer's disease.
The primary endpoint of the trial was time to relapse of Alzheimer's disease agitation as assessed by Kaplan-Meier and hazard ratio, with the key secondary endpoint being percentage
of patients with relapse.

The results showed that AXS-05 significantly delayed the recurrence of agitation symptoms compared with placebo, with a hazard ratio of 0.
275 (p=0.
014) and a 3.
6-fold reduction in the risk of agitation recurrence, and the trial met the primary endpoint
.
The trial also met a key secondary endpoint of a significant reduction in the recurrence of agitation symptoms during double-blind treatment: AXS-05 vs placebo recurrence rate 7.
5% vs 25.
9%（p=0.
018）
。 In addition, a significant improvement in total CMAI scores (p<0.
001) was rapidly observed in the first week of open-label treatment, with a decrease of 11.
0 points (p<0.
001) from baseline in the second week and 20.
6 points (p<0.
001)<b12> in the fifth week.
Clinical healthcare workers have also reported rapid and substantial improvement in Alzheimer's disease agitation, according to the mADCS-CGIC scale, AXS-05 After treatment, 66.
3% of patients improved by week 2 and 86.
3% by week 5
.
The PGI-C scale shows, AXS-05 By the second week of treatment, agitation improved
in 67.
5% and 89.
3% of patients.

In 2022, data from the phase III trial GEMINI (NCT04019704) were updated again, and AXS-05 showed rapid, definitive and statistically significant improvements compared to placebo in depressive symptoms and induction of remission The 6-week MADRS score was more pronounced than the baseline change (-15.
9 vs -12.
0，p=0.
002）
。 In August, AXS-05 (AUVELITY, dexromethorphan + bupropion) sustained-release tablets were approved by the FDA for the treatment of major depressive disorder, and AXS-05 became the first and only oral NMDA receptor antagonist approved for major depressive disorder; At the same time, AXS-05 is the first oral antidepressant
with a new mechanism of action in nearly 60 years.

NO.
7 Gepotidacin treats women with uncomplicated urinary tract infections EAGLE-2 and EAGLE-3 in adults and adolescents

Research Company: GSK

Clinical significance: The first innovative oral antibiotic for the treatment of simple urinary tract infections in 20 years

In November 2022, GSK announced that it would suspend it early, as recommended by the Independent Data Monitoring Committee (IDMC).
gepotidacin was used in patient recruitment
in two pivotal phase III trials EAGLE-2 (NCT04020341) and EAGLE-3 (NCT04187144) in women adults and adolescents for the treatment of uncomplicated urinary tract infections.
This decision was based on pre-set interim efficacy and safety data analysis of 3000 patients, compared with nitrofurantoin and gepotidacin in two similar phase III trials, EAGLE-2 and EAGLE-3 After treatment, the primary efficacy endpoint
of clinical and microbial remission was achieved.

Isolated urinary tract infections (uUTIs) are the most common outpatient infection, with more than half of women developing uUTIs in their lifetime, and more than a quarter of women having recurrent uUTIs
.
EAGLE III The phase plan includes three clinical trials: EAGLE-2 and 3 are similar trials that together will provide substantial clinical evidence
.
EAGLE-2 and EAGLE-3 were all non-inferior uUTI trials comparing gepotidacin (1500 mg orally twice daily for 5 days) with nitrofurantoin (100 mg orally twice daily for treatment 5 days) for effectiveness and safety, the trial lasted about 28 days
.
The primary clinical endpoint was a combination of clinical and microbial response rates
consistent with urinary tract pathogens at TOC follow-up.

Final follow-up and data collection for EAGLE-2 and EAGLE-3 will be completed in the first quarter of 2023 and GSK in 2023 In the first half of the year, a regulatory application
for gepotidacin was submitted to the regulator.
Gepotidacin is a novel triazacenaphene type II topoisomerase inhibitor, different from quinolone antibiotics, Gepotidacin works by inhibiting the binding mode of DNA cyclotronase and topoisomerase IV, with a broad spectrum of antibacterial activity
.

Currently, there have been no new oral antibiotics for the treatment of uncomplicated urinary tract infections (uUTIs) for 20 years, and gepotidacin is expected to become the first new oral antibiotic
to treat uUTIs in 20 years.

NO.
8 Tirzepatide for the treatment of obesity SURMOUNT-1

Research Company: Eli Lilly

Clinical significance: The first drug to reduce body weight by more than 20% on average in a phase III clinical trial

IN APRIL 2022, ELI LILLY PUBLISHED KEY DATA
FROM THE PHASE III SURMOUNT-1 (NCT04184622) TRIAL OF TIRZEPATIDE FOR THE TREATMENT OF OBESITY 。 The SURMOUNT-1 study, the first global phase III registry study conducted by tirzepatide in obese patients, enrolled 2539 obese or overweight patients with at least one disorder (hypertension, dyslipidemia, obstructive sleep apnea syndrome, or cardiovascular disease, but not diabetes) to assess the efficacy and safety differences in weight loss efficacy and safety of adding tirzepatide plus placebo to a low-calorie diet and enhanced exercise
。

Participants were grouped into 1:1:1:1, with the starting dose of 2.
5 mg once a week for Tirzepatide, and then increasing the therapeutic dose to 5 mg and 10 mg of the target dose in increments of 2.
5 mg every 4 weeks, respectively.
15 mg and maintenance therapy until 72 weeks
.
The composite endpoints set by the study were tirzepatide 10 mg and 15 mg dose groups at 72 weeks, and the percentage of patients who lost more than 5% of weight were superior to placebo
.

The results showed that 5mg tirzepatide vs 10mg tirzepatide vs 15mg tirzepatide vs Mean body weight reduction of placebo was 16.
0% versus 21.
4% versus 22.
5% versus 2.
4%
compared with baseline.
In addition, 89 versus 96 versus 96 percent of patients with a weight loss of more than 5 percent vs 28%
。 The proportion of patients with a weight reduction of more than 20% was 55% (10 mg) vs 63% (15 mg) versus 1.
3%, achieving a dual primary and critical secondary endpoint
.

Tirzepatide, the first GIP/GLP-1 receptor agonist approved by the FDA, achieved better HbA1c reduction in the phase III SURGE trial compared with various positive drugs (including semeglutide, dulaglutide, insulin glargine, and insulin degludec
).
。 The SURMOUNT-1 study once again makes tirzepatide the first drug to reduce weight by more than 20% on average in a Phase III clinical trial, and Eli Lilly plans to begin rolling weight loss submissions in 2022 and complete the submission
shortly after the launch of Phase 3 data from the SURMOUNT-2 trial around April 2023.

NO.
9 DCVax-L for the treatment of newly diagnosed or recurrent glioblastoma stage III

Research Company: Northwest

Clinical significance: The first glioblastoma immunotherapy

In November, Northwest Biotherapeutics (NW Bio) announced that its phase III study of dendritic cell therapy DCVax-L in patients with newly diagnosed or recurrent glioblastoma (nGBM/rGBM) met the primary endpoint of significantly prolonging patient median survival and the "long tail" of the survival curve, the results of which were published simultaneously in JAMA Oncology magazine
.

Glioblastoma (GBM) is the most common and deadly type of primary brain cancer, with a recurrence rate of nearly 100%.

Patients with GBM typically relapse within 6-8 months after initial surgery, with an average survival of only 15-17 months after diagnosis, and a 5-year survival rate of only 5.
7%.

The study (NCT00045968) spanned more than 20 years and included a total of 331 patients in two cohorts, DCVax-L (n=232) and placebo (n=99), of which 64 patients in the placebo group received DCVax-L after relapse
.
The initially intended primary endpoint was progression-free survival (PFS), but NW Bio considered this indicator insufficient to measure efficacy and later redefined the indicator as overall survival (OS) in patients with nGBM, with a secondary endpoint of OS
in patients with rGBM.

The results showed that in the nGBM cohort (n=232), the median OS of patients in the DCVax-L group was 19.
3 months (22.
4 months after surgery) and 16.
5 months in the control group (HR=0.
80, p=0.
002).

In addition, the 48-month survival rates for DCVax-L and control patients were 15.
7% and 9.
9%, respectively, and 13% and 5.
7%
at 60 months, respectively.

In the rGBM cohort (n=64), the median OS was 13.
2 months in the DCVax-L group and 7.
8 months in the control group (HR=0.
58, p<0.
001).

In addition, the 24-month survival rates for patients in the DCVax-L and control groups were 20.
7% and 9.
6%, respectively, and 11.
1% and 5.
1%
at 30 months.

In more than 400 clinical trials since 2005, more than 32,000 patients have tested different treatments, with only one nGBM A survival benefit was demonstrated in phase III trials, and none of the phase III studies in the field of rGBM achieved 8 survival benefits
.
DCVax-L is the first dendritic cell vaccine to publish the results of phase III studies, the first phase III study in nearly 20 years to demonstrate that immunotherapy can successfully prolong the survival of nGBM patients, and the first phase III study
to significantly extend the survival of rGBM patients in nearly 30 years.

NO.
10 Tumor vaccine mRNA-4157 combined with pembrolizumab for the treatment of melanoma KEYNOTE-942/mRNA-4157-P201

NO.
10 Tumor vaccine mRNA-4157 combined with pembrolizumab for the treatment of melanoma KEYNOTE-942/mRNA-4157-P201mRNA-4157 combined with pembrolizumab

Trial company: Moderna/Merck

Clinical significance: The first randomized clinical demonstration of the efficacy of mRNA in cancer treatment

In December 2022, Moderna and Merck announced the key results of the Phase IIb KEYNOTE-942/mRNA-4157-P201 trial of mRNA-4157/V940 in combination with pembrolizumab for adjuvant therapy in patients with stage III/IV melanoma after complete resection, demonstrating statistically significant and clinically significant improvements in the primary endpoint of recurrence-free survival (RFS) compared with pembrolizumab monotherapy
。

mRNA-4157/V940 is a novel investigational personalized cancer vaccine based on messenger ribonucleic acid (mRNA) consisting of a single synthesized mRNA encoding up to 34 neoantigens These neoantigens are algorithmically designed based on the unique DNA sequence mutation characteristics of each
patient's tumor.

KEYNOTE-942/mRNA-4157-P201 is an open-label Phase IIb trial with 157 patients enrolled and randomized to receive mRNA-4157/V940 (9 doses every 3 weeks) with pembrolizumab (200 mg every 3 weeks), or pembrolizumab
alone.
The primary endpoint was recurrence-free survival, and the secondary endpoint included distal metastasis-free survival and overall survival
.
Data analysis showed that cancer vaccine versus pembrolizumab reduced the risk of recurrence or death by 44% after complete tumor resection in patients with stage III/IV melanoma compared with pembrolizumab monotherapy (HR: 0.
56, 95% CI: 0.
31-1.
08, one-sided p-value = 0.
0266).

The KEYNOTE-942/mRNA-4157-P201 study results are the first to demonstrate the efficacy of investigational mRNA cancer treatment in a randomized clinical trial, and the two companies plan to discuss the results with regulatory agencies and initiate a phase III study for melanoma in 2023 and rapidly expand to other tumor types
.

Of course, any clinical study has different interpretations, but positive clinical progress is always worth looking forward to
.
2022 has become the past, "thousands of clinical trials, after all, you can only glimpse one or two", what breakthrough progress will be made in 2022 and what expectations will be in 2023, you may wish to leave a message to discuss
.

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