MSI-H/dMMR advanced solid tumors: how does each PD-1/PD-L1 perform?

On November 16, 2020, Synaptic Pharmaceuticals announced a new drug listing application (KN035) for a recombinant humanized PD-L1 monometric antibody Nvolly monoantigen injection (KN035) in a strategic partnership with Corning Jerry Biopharmaceuticals and ThinkDi Pharmaceuticals (KN035) The NDA has been formally submitted to the National Drug Administration (NMPA) for the treatment of advanced colorectal cancer, stomach cancer and other mismatched repair functional defects (dMMR) advanced solid tumors for the treatment of microsatellite instability (MSI-H) that has failed in the past.
stone stirred a thousand waves, the news was announced, it caused the pharmaceutical industry to pay high attention.
past, anti-tumor drugs have often been marketed to identify tumor types by source, such as for the treatment of "lung cancer," "kidney cancer," "breast cancer," "liver cancer" and so on.
in the field of colorectal cancer, studies of MSI-H patients have been conducted since 2015, especially with keynote-016 and Checkmate-142 as two heavyweight studies that kicked off the "MSI era" of immunosuppressant therapy.
Although there are no immuno-checkpoint inhibitors on the market in this adaptation, but there have been many enterprises have also carried out anti-PD-(L)1 monoantigen for MSI-H/dMMR solid tumor clinical research layout.
is the world's first off-the-skin injection of PD-L1 inhibitors, and the NDA marks the official "entry" of home-grown immuno-checkpoint inhibitors into open-ended cancer-resistant adaptations.
at this exciting time, this article specifically reviews the previous cultivation process of combing K medicine, O medicine, as well as the local IO new force Nwoli monoanti, Terelli pearl monoanti, Karelli pearl monoantigen in MSI-H/dMMR advanced solid tumor of the latest disclosure data.
if there are any omissions, readers are welcome to add.
MSI-H/dMMR Advanced Solid Tumor Adaptation Progress (Source: NextPharma Database) Pabli Pearl Monoanti (Approved for First, Second and Above Treatment) May 23, 2017, FDA Accelerates Approval of Pabli Pearl Single Anti(K-drug) is used to treat adult and child patients with non-removable or metastatic MSI-H/dMMR solid tumors who have progressed after treatment and who have no satisfactory alternative treatment options, as well as to treat non-removable or metastatic MSI-H or post-treatment progression of dMMR colorectal cancer.
, the K drug became the first FDA-approved anti-tumor therapy to be differentiated by biomarkers by tumor source, a landmark.
K drug approval process (source: CCR) K drug approval is based on data from five clinical trials: KN-012, 028, 016, 158, and 164.
all patients receive K medicine 10 mg/kg i.v. once every 2 weeks or 200 mg i.v. every 3 weeks for a maximum of 24 months until there is unacceptable toxicity or disease progression.
end-of-life indicators were evaluated by the Radiologist Review of the Independent Centre for Blind Law, based on RECIST1.1 ORR.
149 patients were identified as MSI-H/dMMR cancers in five clinical studies that provided data on applications for listing (source: CCR), including 90 MSI-H/dMMR mCRC patients and 59 other MSI-H/dMMR cancer patients (14 different cancer types).
identified 59 patients with objective remission from 149 patients, with ANR of 39.6% (95% CI, 31.7-47.9) and complete remission (CR) of 7%.
duration ranged from 1.6 months to 22.7 months, with 78% of mitigation durations exceeding 6 months.
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June this year, the high-profile KN-177 study was reported orally in the role of LBA4 at the ASCO Plenary session, another milestone in the immunotherapy of colorectal cancer.
results show that, compared with pure chemotherapy/targeted therapy, first-line immunotherapy of K-drug brought clinically significant and statistically significant PFS improvement to MSI-H-type mCRC patients, with a 1x increase in the medium PFS (16.5 months vs 8.2 months) and as low as 0.6 HR (95% CI, 0.45-0.80; P-0.0002) is such a significant risk ratio for differences never seen in the first-line treatment research of mCRC in recent years.
, immunotherapy received a longer-lasting treatment response than chemotherapy alone, and the overall therapeutic toxicity was significantly reduced.
, the FDA approved the K drug for first-line treatment in patients with non-removable or metastatic MSI-H or dMMR colorectal cancer.
Navuliyu monoant±i(approved second-line and above treatment) is less than three months away from K drug approval for unlimited cancer-type adaptation, FDA accelerated approval of Navuliyu single on August 1, 2017 Anti-(O-drug) for patients with metastatic colorectal cancer (mCRC) in people or children (≥12 years of age) who develop the disease after the treatment of fluorouracil, oxalipari and olithycon.
it is clear that the biggest competitor to the immuno-checkpoint inhibitor single-drug treatment of CRC is O. the approval of
O drugs was mainly based on a multi-center, non-random, multi-parallel control, open-label Phase II clinical study CheckMate-142, a total of 74 patients received O-drug treatment (3mg/kg, intravenous injection, every two weeks), the main endpoint of the study is ORR.
the results of a single-drug queue published in The Lancet Oncology in September 2017, the researchers assessed ORR at 31.1% (23/74), disease control (DCR) at 69%, patients with disease control for more than 12 weeks, PFS for 12 months at 50%, and OS73% for 12 months.
March 2018, the Journal of Clinical Oncology (JCO) updated data from the Ipimu monoantigen combination of O-drug treatment cohorts in the CheckMate-142 study, and the IO/IO combination showed better results than immunodosive therapy.
: Based on the PFS (A) and OS (B) Kaplan-Meier graphs assessed by the researchers, compared to the nivolumab single-drug queue and nivolumab plus ipilimumab queue (with similar mid-follow-up time) in the CheckMate-142 study, the researchers assessed ORR of 55%, DCR rate of 80%, DCR? The proportion of patients at 12 weeks was 80%, 12-month PFS rate was 71%, 12-month OS rate was 85%, and the patient's efficacy was not related to PD-L1 expression, BRAF/KRAS mutation status, or Lynch syndrome.
the results suggest that the combined O-Y solution could be used as a new treatment option for dMMR/MSI-H-type mCRC patients.
this, in July 2018 the FDA further approved the second-line treatment of MSI-H/dMMR metastatic colorectal cancer adaptation in the combination of Opdivo-Vervoy (PD-1-CTLA-4).
Nwoli Monoanti (NDA Filing Phase) On November 16, Nvolly Monoanti formally filed an NDA declaration, based primarily on its single-drug treatment of microsatellite instability (MSI-H)/mismatch repair functional defect (dMMR) advanced solid tumor Phase II.critical clinical trial data (NCT03667170).
the safety and preliminary efficacy results of the study were first presented at the 2020 annual meeting of the American Society of Clinical Oncology (ASCO), and the updated results were presented at the annual meeting of the Chinese Society of Clinical Oncology (CSCO) at the end of September.
the study used a one-arm open label design, and the main endpoint of the study was the independent review committee (BIRC) evaluation of the confirmed objective mitigation rate (ORR).
the MSI-H status of colorectal cancer (CRC) and stomach cancer (GC) was confirmed by central pathology, and the dMMR status of other tumors was assessed locally.
Enwoli mono-anti-treatment MSI-H/dMMR solid tumor efficacy (Source: Medical Oncology Channel) As of June 19, 2020, a total of 103 patients in the study group, BIRC assessed confirmed ORR in late CRC, advanced GC, other solid tumors and all populations were 43.1%, 44.4 , 40.0% and 42.7%; the average BIRC-assessed medium remission time (DOR) was not achieved, with a 12-month DOR rate of 92.2%, the medium disease-free progression period (PFS) was 11.1 months, and the medium survival (OS) was not achieved, and the 12-month OS rate was 74.6%.
16% of the adverse events associated with 3/4-level treatment and 8% of the 3/4 level of immuno-related adverse events.
conducted a multi-center, open phase 1/2 clinical study (CTR20160872) for patients with single-drug treatment of patients with advanced solid tumors in China, consisting of phase 1 dose verification and phase 2 adaptation expansion.
specific disease subgroups of the extended part of the disease include MSI-H and dMMR solid tumors.
data published in the 2018 CSCO came from 22 patients in subgroups, of whom 14 were identified as MSI-H/dMMR tumors by 14 centers, including 12 patients with colorectal cancer, for efficacy assessment.
as of May 11, 2018, the efficacy assessment was still early, with an objective remission rate of 29% (4 rectal cancer patients), and the medium duration of remission was still in maturity and overall had good tolerance.
A forward-looking open clinical study (ChiCTR-17013249) of late-stage or metastasis solid tumors led by Professor Gao Yong of Tongji University-affiliated Oriental Hospital was published online in the Journal of Cancer Research and Clinical Oncology.
: From baseline tumor load changes In this study, solid tumor patients identified as dMMR/MSI-H received kareliju monoantigen resistance of 200 mg, 2 weeks, continuous medication for up to 2 years or disease progression.
as of October 30, 2019, of the 12 patients assessable, including 5 cases of colorectal cancer, 2 had reached CR, 6 had reached PR, ORR had reached 66.7% and the disease control rate was 100%.
12-month PFS rate was 83.3% and the 12-month OS rate was 90%.
dMMR/MSI-H solid tumor patients initially demonstrated good effectiveness and reliable safety.
reference to domestic and foreign test data, we can see that in the Keynote-177 study, the group of patients with DMMR/MSI-H advanced colorectal cancer treated with Paboliju monodratives, ORR was 43.8%, DCR was 64.7%, 12-month PFS was 55.3%, and in the CheckMate-142 study, Navuliyu single-drug R was 32%, DCR was 69%, 12-month PFS was 50%, 12-month OS was 73%, which seemed "slightly inferior", while the combined O-Y treatment queue "pulled back" with better performance, with the researchers assessing ORR at 55%, DCR at 80%, 12-month PFS at 71% and 12-month OS at 85%.
key clinical study of Enwoli Monoantigen II. (n=103), the ORR of the mCRC queue was 43.1%, the 12-month OS rate was 72.9%, the ORR was 42.7% for all populations, and the 12-month OS rate was 74.6%.
29% of the early efficacy assessment in the 1/2 study of 1/2 of the reilly-pearl monoanti-resistance (n-14).
the preliminary study of Karelli's single resistance (n-12) showed that the ORR reached 66.7% and the 12-month PFS rate was 83.3%.
Of course, the above-mentioned domestic PD-1/PD-L1 data is not the final clinical data, the sample size is less, not head-to-head comparison, only in the current data to spy on the potential clinical effectiveness differences, welcome readers in the comments in the message area supplement.
, talk a little bone-chilling off-topic.
Although there is a basic consensus in the industry that all colorectal cancer patients should be screened for MSI status, anti-tumor therapies differentiated by biomarkers still face difficulties in clinical landing, most clinicians still do not understand the definition of MSI and the significance of its reporting, and generally do not know the specific methods of MSI testing.
In May 2019, china's first "China Expert Consensus on Microsatellite Instability Detection of Colorectal Cancer and Other Related Solid Tumors" was officially published in the Journal of Practical Oncology, which expounds and recommends the advantages and shortcomings of 3 types of detection methods, including immunosomal chemical detection MMR protein, multifluorescent polymerase chain reaction (PCR) detection microsatellite bits and MSI algorithms based on second-generation sequencing (NGS) platforms.
what the future of MSI-H/dMMR advanced solid tumor precision treatment will be like, let's wait and see! Medical Rubik's Cube Source: Pharmaceutical Rubik's Cube Copyright Notice: All text, images and audio and video materials on this website that indicate "Source: Met Medical" or "Source: MedSci Original" are owned by Metz Medicine and are not authorized to be reproduced by any media, website or individual, and are authorized to be reproduced with the words "Source: Mets Medicine".
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