2022 "Unlimited Cancer Species" Broad Spectrum Anti-Cancer Drugs Open a New Chapter! 25 "Star Drugs" information summary

Surgical treatment, which began in the early 19th century, has been continuously developed to achieve the goal of "curing" a small number of patients; radiation therapy, which began at the end of the 19th century, developed into the 1950s, and the role of individual or combined action made about 1/3 of patients cured; chemotherapy, which began in the early 20th century, further improved the treatment effect of tumors. Three traditional treatments are going to the extreme, but they are far from meeting the desired therapeutic goals.

With the advent of the era of "precision medicine", based on specific gene mutations and biomarker types, the successful development and listing of "unlimited cancer" broad-spectrum anti-cancer drugs have made the entire medical community and patient circle boil. Because since then, whether it is a common cancer or a rare cancer, whether it is early or advanced, as long as specific conditions are met, it is possible to regain a new life through these broad-spectrum anti-cancer drugs. Drugs that are not limited to cancer species open a new chapter in tumor treatment.

Five FDA-approved new drugs with no limit on cancer

1

May 2017

Keytruda (PD-1) became the world's first immune drug that does not distinguish between tumor sources;

2

November 2018

Vitrakvi was approved for marketing as the world's first broad-spectrum targeted drug with unlimited cancer species for solid tumor patients with NTRK fusion;

3

August 2019

Rozlytrek was approved for marketing, becoming the third broad-spectrum anti-cancer drug in the world that does not distinguish between tumor sources

4

May 2020

The legendary anti-cancer drug LOXO-292 was approved for accelerated marketing for the treatment of three major cancers: advanced RET fusion-positive non-small cell lung cancer, RET mutant medullary thyroid carcinoma (MTC) and RET fusion-positive thyroid cancer.

5

August 2021

On August 18, 2021, dostarlimab-gxly (Jemperli, Dostali maclizumab) was launched, and patients with recurrent or advanced solid tumors with recurrent or advanced solid tumors were previously treated and did not have satisfactory alternative options.

The approval of these five new therapies, due to the amazing clinical data and broad spectrum of anti-cancer effects, quickly spread throughout the circle of cancer friends, so that more lucky patients and so on have come to new hope and treatment options! There are more new anti-cancer drugs with unlimited cancer species, such as TPX-0005, AB-106, AMG510, LOXO-195, etc. are being accelerated to unlock...

Ten targets, 25 solid tumor "star drugs" free drug information summary!

At present, there are many broad-spectrum anti-cancer new drugs with unlimited cancer species in China, and the Medical Department of the Global Oncologist Network has sorted out the relevant information of these drugs for the majority of patients, which can give cancer patients with limited economic conditions the opportunity to receive better treatment.

Target one: NTRK

In the past two years, the hottest anti-cancer drug in addition to PD-1 is the NTRK inhibitor. In November 2018, the entire medical community and cancer circles boiled over Vitrakvi ® (larotrectinib), the world's first targeted drug for NTRK that does not distinguish between tumor sources, which was newly approved by the FDA. This new anti-cancer drug can help thousands of people every year, and its launch has given new hope to patients around the world. Many NTRK fusion cancer patients have been miraculously reborn after receiving treatment! Since then, another "diamond" target gene, NTRK, has rapidly spread throughout the circle of cancer friends, opening a new era of pan-cancer treatment!

Lalotinib

Drug Name: Larotrectinib (Vitrakvi, larotrectinib)

Target: NTRK mutation

R&D company: Bayer

Drug Introduction: Lalotinib is the world's first targeted drug that does not distinguish between tumor sources for initial treatment, and since it was approved for marketing in November 2018, it has brought new hope and choice to doctors and patients in the global oncology community.

The biggest attraction of the drug is that it is a new anti-cancer drug that targets specific genetic mutations, not specific cancer types. The NTRK gene fusion solid tumors it can treat include 17 cancer types such as breast cancer, colorectal cancer, lung cancer, and thyroid cancer, and can be used in both adults and children.

Indications: Adult or pediatric solid tumor patients with NTRK fusion

Emtricidinib

Drug Name: Entrectinib ( Rozlytrek, RXDX-101 )

Targets: NTRK, ROS1, ALK

R&D company: Roche

Drug Introduction: On August 16, 2019, the FDA accelerated the listing of the world's third broad-spectrum "cure line" anticancer drug Enterinib for the treatment of adult and pediatric patients with neurotrophic myosin receptor kinase (NTRK) fusion positive, locally advanced or metastatic solid tumor progression after initial treatment or no standard treatment regimen, and ROS1-positive non-small cell lung cancer (NSCLC) patients.

Indications: First- or second-line treatment of ROS1 mutation-positive lung cancer; patients with NTRK fusion solid tumors

TPX-0005

Drug Name: TPX-0005 (Repotrectinib, Repotinib)

Target: ALK/ROS1/NTRK mutation

R&D company: TurningPoint/Zaiding Pharmaceutical

Drug description: Second-generation ALK/ROS1/NTRK inhibitors. This new generation of ROS1, pan-TRK and ALK inhibitors is a specially designed low molecular weight large ring TKI with high selectivity and high potency against ROS1, TRKA-C and ALK. Clinically proven anti-ROS1 ability can reach more than 90 times that of clozotinib and entrectinib (Etreso)! Among patients with ROS1 fusion, one-third of patients receiving crotinib developed present ROS1 G2032R, and a further 5% developed ROS1 D2033N. TPX-0005 is able to overcome all known ALK, ROS1 and NTRK resistance problems that arise in the clinic.

Indications: First- or second-line treatment of ROS1 mutation-positive lung cancer; adult and pediatric patients with NTRK fusion solid tumors

AB-106

Drug Name: Taletrectinib (DS-6051b/AB-106)

Target: ROS1/NTRK mutation

Drug description: Second-generation ROS1/NTRK inhibitors. Talectrectinib, code-named DS-6051b/AB-106, is a new, effective, and highly selective next-generation ROS1 and NTRK dual-target small molecule inhibitor that crosses the blood-brain barrier.

ICP-723

Drug Name: ICP-723

R & D company: Nuocheng Jianhua

Drug Introduction: ICP-723 is a domestically developed second-generation pan-tyrosine receptor kinase (pan-TRK) small molecule inhibitor for the treatment of neurotrophic tyrosine kinase (NTRK)-positive tumor patients with different tumor types and patients who are resistant to first-generation tyrosine kinase (TRK) inhibitors due to mutations in the resistant TRK gene. On August 31, 2021, it received approval from the U.S. Food and Drug Administration (FDA) to begin Phase I clinical trials in the United States.

Indications: Adult solid tumor patients with NTRK fusion

06

TL118

Drug name: TL118

R & D company: Suzhou Taoluo

Drug introduction: TL118 capsule is a first-generation domestic "unlimited cancer species" NTRK fusion gene mutation targeting drug. At present, clinical trials of TL118 for the treatment of advanced NTRK fusion solid tumors have been carried out in China.

07

YES-1803

Drug name: SIM-1803

Target: NTRK/ROS1/ALK

R&D company: Simcere Pharmaceuticals

Drug Introduction: SIM-1803 is a self-developed second-generation anti-tumor NTRK multikinase small molecule inhibitor, which can potentially target NTRK, ROS1 and ALK primary mutations and NTRK, ROS1 secondary drug resistance mutations, has obtained clinical approval for new drugs, and has officially launched Phase I clinical trials in China and recruited patients.

08

HG030

Drug name: HG030

Target: NTRK/ROS1

R & D company: Chengdu pilot

Drug Introduction: HG030 is a novel structure, highly active, highly selective second-generation Trk oral small molecule inhibitor, and also has inhibitory activity against ROS1. Preclinical research data show that HG030 has good drug-ready properties, and excellent anti-tumor activity is demonstrated in a variety of tumor models carrying Trk mutations and ROS1 On March 30, 2020, according to the drug evaluation center of the State Food and Drug Administration of China, the small molecule tyrosine kinase inhibitor HG030 has obtained clinical trial license. Clinical trials have been officially conducted and patients are being recruited.

09

BPI-28592

Drug name: BPI-28592

Target: NTRK

R&D company: Beida Pharmaceutical

Drug Introduction: BPI-28592 is a new powerful and highly selective protomyosin receptor kinase second-generation oral small molecule inhibitor that can cover a variety of cancer species and is intended for the treatment of patients with locally advanced or metastatic solid tumors carrying TRK gene variants.

10

VC004

Drug name: VC004

R&D company: Wikell

Drug introduction: VC004 is a second-generation TRK inhibitor independently developed by mainland China, which is clinically used to treat solid tumors with NTRK gene fusion mutations. By targeting the binding protomyosin receptor kinases TrkA, TrkB, and TrkC, the signal amplification and conduction of pathways downstream of kinase activation, such as PI3K, RAS/MAPK/ERK, and PLC-gamma, are blocked, thereby inhibiting tumor growth.

11

FCN011

R&D company: Fuchuang Pharmaceutical

Drug Introduction: FCN011 is the first generation of innovative small molecule chemical drugs independently developed by Mainland China, which is intended for the treatment of solid tumors with NTRK gene fusion positive.

12

LPM4870108

Drug name: LPM4870108

R&D company: Luye Pharmaceutical

Drug Introduction: LPM4870108 is a highly selective second-generation NTRK inhibitor that is effective for both wild-type and acquired drug-resistant mutations, and is intended to be used to treat "solid tumor patients with NTRK gene fusion and its drug-resistant mutation positivity". It is expected to cover all relevant indications of the first generation of the same target products that have been marketed, and also cover the treatment of patients with congenital or post-drug resistance of the first generation of inhibitors, that is, first- and second-line treatments for patients with NTRK gene fusion solid tumors, with a wider range of indications.

13

XZP-5955

Drug name: XZP-5955

R & D company: Xuanzhu Biology

Drug introduction: XZP-5955 tablets are the dual inhibitors of TRK and ROS1 targeted by the second generation of domestic products. According to a study published in AACR 2020, XZP-5955 showed high performance against multiple TRK and ROS1 resistance mutations, including TRKA G595R (IC50=2.2nM), TRKA G667C (IC50=1.0nM), TRKC G623R (IC50=4.7nM) and ROS1 G2032R, which also showed high performance IC50 < 0.05 nM) and also effectively inhibited the expression of carcinogenic NTRK or ROS1 Proliferation of rat BaF3 cells with fusion and its resistance variants such as TRKA G595RTRKC G623RTRKA G667C and ROS1 G2032R with high potency

14

TQB-3558

Drug name: TQB-3558

R & D company: Chia Tai Tianqing

Drug Introduction: TQB-3558 is the first generation of innovative small molecule chemical drugs independently developed by Mainland China, which is intended for the treatment of solid tumors with NTRK gene fusion positive.

15

TQB-3811

Drug name: TQB-3811

Drug Introduction: TQB-3811 is a second-generation TRK inhibitor independently developed by Chia Tai Tianqing, which is clinically used to treat solid tumors with NTRK gene fusion mutations.

Target two: BRCA1/2

The BRCA1/2 gene is a tumor suppressor gene, and in recent years, more and more research has been conducted on this target, and PARP inhibitors have become the well-deserved "nemesis" of BRCA mutant tumors. At present, a number of PARP inhibitors have been approved for marketing by the FDA, including most of the cancers that may be caused by BRCA mutations, such as breast cancer, pancreatic cancer, prostate cancer, ovarian cancer, fallopian tube cancer, primary peritoneal cancer, etc. In addition, China has also increased the research and development of PARP inhibitors.

16

HWH-340

Drug name: HWH-340

Target: BRCA1/2, etc. (HRD)

Drug Introduction:

There are many causes of homologous recombinant repair defects (HRD), including brca1/2 mutations in the embryonic line, BRCA1/2 mutations in the system, HRR mutations, etc. BRCA mutations often detected in cancer genetic testing are only one of the reasons for homologous recombinant repair defects.

HWH340 is a PARP inhibitor, but unlike most PARP inhibitors, this drug can be used to treat cancer patients with homologous recombinant repair defects caused by various reasons.

17

HTMC0435

Drug name: HTMC0435

Target: BRCA1/2, etc

Drug introduction: Non-clinical research results show that HTMC0435 is a highly effective and selective inhibitor of PARP1 and PARP2, which is stronger than Olaparib in inhibiting the activity of PAPR enzyme in vitro and proliferation of a variety of tumor cells in vitro, and the tumor inhibition effect on a variety of in vivo transplant tumor models (especially the tumor model with BRCA1/2 mutation) is also significantly better than that of Olaparib, which can cause complete tumor regression. At the same time, HTMC0435 also has good pharmacokinetic characteristics, and the safety risk is also within the acceptable range.

18

CVL218

Drug name: CVL218

Target: BRCA1/2

Drug Introduction: CVL218 is a broad-spectrum anticancer drug for a variety of advanced or metastatic malignancies, which is a PARP inhibitor, mainly for patients with BRCA1 or BRCA2 gene mutations. Although not all of the cancers currently being recruited are solid tumors, they basically cover common cancers, including breast cancer, prostate cancer, lung cancer, bladder cancer, stomach cancer, bowel cancer, biliary tract tumor, pancreatic cancer, melanoma, glioma and so on.

Target three: Claudin 18.2

Claudin 18.2 is a subtype of the tight concatenatin family and is highly expressed in a variety of tumor tissues, such as gastric cancer (60% to 80%), pancreatic cancer (50%), esophageal cancer (30% to 50%), and lung cancer (40% to 60%), but it is almost not expressed in normal tissues, so it has excellent therapeutic potential. Even in gastric cancer metastases, Claudin 18.2 has a high level of expression, which makes Claudin 18.2 a promising new target for targeted therapy and immunotherapy.

19

AB011

Target of action

Claudin 18.2

Recruitment Information

Gastric cancer target rookie, star of hope for more than 50% of patients! Claudin 18.2 New Drugs Fill the Treatment Gap!

Referral index

★★★★★

CAR-T cell therapy belongs to the category of immunotherapy, and so far, it has shown excellent efficacy in treatments including leukemia and lymphoma, and many therapies have been listed.

Claudin 18.2 is an emerging target for gastric cancer, with a detection rate of nearly 60% of all stomach cancers. CAR-T cell therapy, combined with the Claudin 18.2 target, maximizes coverage of a wide range of patients who have failed or are resistant to standard therapy.

Target Four: BRAF V600E

BRAF mutations may be seen in multiple cancers, about 50% to 70% of malignant melanoma, 40% to 70% of papillary thyroid cancer, 35% to 60% of ovarian cancer, 5% to 15% of colorectal cancer, 1% to 3% of patients with non-small cell lung cancer have BRAF mutations, accounting for about 8% of all malignant tumors. BRAF V600E is the most common subtype of BRAF mutations.

20

RX-208

BRAF V600E

Preliminary evaluation of the antitumor efficacy of RX208 in patients with braf V600E mutation-positive advanced malignant solid tumors

RX208 is a selective small molecule inhibitor drug for BRAF V600E mutation, independently developed by Runxin Biotech. RX208 is the third class 1 new drug independently developed by Runxin Bio to enter clinical trials after RX108 (a new small molecule Na+/K+-ATPase inhibitor) and RX518 (the third generation of new small molecule epidermal growth factor receptor tyrosine kinase inhibitor [EGFR-TKI]). RX208 has the advantages of strong drug activity and high selectivity, and is expected to be developed into a safer and more effective BRAF V600E mutant small molecule inhibitor in the future, benefiting more patients.

Target 5: PI3K/mTOR

The PI3K-Akt-mTOR pathway plays a vital role in various physiological processes such as cell growth, differentiation, and apoptosis, and abnormal signaling pathways may occur in various cancer species. PI3K is the upstream of the channel, mTOR is the downstream of the channel, and there is drug research and development. Three-negative breast cancer, gastric cancer, small cell lung cancer and other cancers that are currently not well targeted therapy may have a certain proportion of PI3K-Akt-mTOR pathway abnormalities, so targeted drugs for this pathway have the therapeutic potential of multiple carcinoma species or pan-cancer species.

21

WX390

PI3K/mTOR

Evaluate the safety and tolerability of WX390 in the treatment of patients with advanced malignant solid tumors or lymphomas, and explore the maximum tolerated dose to determine the recommended dose for phase II clinical trials.

WXFL10030390 (WX390) is a small molecule inhibitor drug targeting PI3K/mTOR targets, developed by Jiatan Pharmaceuticals. The PI3K-Akt-mTOR pathway plays a vital role in various physiological processes such as cell growth, differentiation, and apoptosis, and abnormal signaling pathways may occur in various cancer species. PI3K is the upstream of the channel, mTOR is the downstream of the channel, and there is drug research and development. Three-negative breast cancer, gastric cancer, small cell lung cancer and other cancers that are currently not well targeted therapy may have a certain proportion of PI3K-Akt-mTOR pathway abnormalities, so targeted drugs for this pathway have the therapeutic potential of multiple carcinoma species or pan-cancer species.

22

RX-108

Solid tumor with PI3K mutation, STK11

RX108 is a new small molecule Na+/K+-ATPase inhibitor independently developed by Runxin Biotech. Na+/K+-ATPase is the main target of cardiac glycosides, new studies have shown that it is related to the occurrence, development, migration and differentiation of tumor cells, inhibition of Na+/K+-ATPase can exert anti-tumor effects through a variety of pathways, opening up a new way for the development of new anti-tumor drugs.

Target Six: HER2

23

Previtinib

HER2

Tolerability and pharmacokinetics of pvitinib in patients with HER2 expression-positive advanced solid tumors: a phase I.A clinical study of single-arm, open-end, dose-climbing design with single and multiple administration

Prevettinib is a new class 1.1 drug independently developed by the mainland, which belongs to a small molecule inhibitor drug, which has a good inhibition of the HER2 target, and its therapeutic effect is similar to that of trastuzumab, and has the potential to treat a variety of solid tumors.

Unlimited targets: chemotherapy, CAR-T, etc

24

CAR-T

Claudin 18.2/MAGE-A4/MSLN/ADAM12/GPC-3

Clinical trials of the safety and efficacy of CAR-T cells in the treatment of advanced solid tumors

CAR-T cell therapy belongs to the category of immunotherapy, and so far, it has shown excellent efficacy in treatments including leukemia and lymphoma, and many therapies have been listed. At present, this clinical trial is spearheaded by a well-known cancer center in China, recruiting patients with various advanced solid tumors.

25

Legubi Star

/(Chemotherapy drugs)

7x complete remission rate! A new drug for pan-cancer chemotherapy, legobicin, was born and is being recruited for clinical trials

Legobicin is a class of new anthracycline chemotherapy drugs independently developed by the mainland, based on the coupling of doxorubicin, which can reduce the cardiotoxicity of the drug and the damage caused to the immune system, while prolonging the half-life of the drug in the patient's body, and at the same time can achieve the dual effect of promoting the anti-tumor immune response while inhibiting tumor growth.

Due to this feature, compared with doxorubicin, lecobicin is less harmful to normal cells, causing less cardiotoxicity, allergy, hemolysis and vascular and muscle irritation, and higher safety. Preclinical trials have confirmed that lecobicin combined with PD-1 inhibitors can achieve a complete remission rate of 7 times that of doxorubicin combined with PD-1 inhibitors! At the same time, legobicin has a good therapeutic effect on intrahepatic lesions and bone metastases. Currently, phase I clinical trials of legobicin are recruiting patients.

More anti-cancer "nova" with unlimited cancer species in the accelerated "unlocking", stay tuned!

In addition to the above-mentioned NTRK gene fusion, BRCA and other genes, a variety of other biomarkers are currently being used to develop "unlimited cancer" therapies, for specific information see the table below:

In addition, there are a number of immune checkpoint inhibitors under development that also show the strength of broad-spectrum anti-cancer, hoping that these drugs can achieve more brilliant results, and there are more affordable anti-cancer drugs to benefit more patients.

I have to say that this is an era full of miracles, many new drugs have been listed, we must strengthen confidence, believe that the future of patients is getting better and better.