The "unlimited cancer" therapy track is winding: Merck, Eli Lilly, Novartis lead, and the cornerstone comes later?

One key, only one lock can be opened? That's not necessarily
.

Recently, according to the official website of CDE, the marketing application of "platinib" of CStone Pharmaceuticals has been accepted (acceptance number: JXHS2200094), and the indication is: first-line treatment of locally advanced or metastatic RET fusion-positive non-small cell lung cancer
.

As a typical "unlimited cancer" therapy, platinib has attracted "unprecedented attention" and has strong market potential: in 2021, platinib and another precision therapy drug Tegihua jointly achieved sales of more than 160 million yuan
.

The "unlimited cancer" therapy has also become an age-old problem of "a key can only open one lock", and has become a "master key"
to unlock various types of cancer.

The "unlimited cancer" therapy track is winding, Merck, Eli Lilly, and Novartis are leading, can the cornerstone come later?

The "unlimited cancer" therapy track is in the limelight

Pratinib (trade name: Pugeva) is an oral, once-daily, potent and highly selective RET inhibitor
.

It was first approved for marketing in the United States for the treatment of non-small cell lung cancer, and has since expanded its indications to medullary thyroid cancer and thyroid cancer
.
Developed by Blueprint Medicines, in June 2018, CStone entered into an exclusive collaboration and licensing agreement with Blueprint Medicines, acquiring exclusive development and commercialization rights
for platinib in Greater China.

In March 2021, platinib was approved for the first time in China for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had previously received platinum-containing chemotherapy with transfection rearrangement (RET) gene fusion, becoming the first highly selective RET inhibitor
approved for marketing in China.

At the same time, platinib has also become the first drug
in China to use real-world data from Lecheng to assist in review and approval.

In March of this year, platinib was expanded to include the treatment of adults and children 12 years of age and older with advanced or metastatic RET mutated medullary thyroid cancer (MTC) requiring systemic therapy, as well as adults and children aged 12 years and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and are refractory to radioactive iodine (if radioactive iodine is applicable
).

It has become the first and only selective RET inhibitor
approved in China for RET mutated medullary thyroid cancer and RET fusion-positive thyroid cancer.

Progress of Pratinib declarations in China

Data source: Pharma Data

CStone once again declared a new indication for the first-line treatment of locally advanced or metastatic RET fusion-positive NSCLC patients
.

Previously presented trial results at CStone Pharmaceuticals at the 2021 ASCO Annual Meeting showed a lasting clinical benefit
in patients with RET fusion-positive NSCLC.

In 68 patients without systemic treatment, the overall response rate (ORR) was 79%.

As the first highly selective RET inhibitor in China, platinib shows strong market potential
.
According to CStone Pharmaceutical's financial report, in 2021, platinib and another precision therapy drug Taijihua jointly achieved sales
of more than 160 million yuan.

This broad-spectrum drug suitable for pan-cancer has attracted the attention of many big pharmaceutical companies
.

Inventory: New therapies for unlimited cancer types worldwide

In the past cognition, targeted drugs and immunotherapy drugs were drugs
that could only be used for specific cancers, specific gene mutations, specific targets, and specific pathways.

Many patients have no ideal target for genetic test results, lose the opportunity to take drugs, or try to take drugs across indications, but cannot be reimbursed or donated across
indications.

With the advent of the era of precision diagnosis and treatment, tumor treatment based on biomarkers rather than tumor types has become a trend, and the successful development and marketing of broad-spectrum anticancer drugs for pan-cancer have brought new hope
for breaking the limitation of cancer types.

At present, what emerging therapies of unlimited cancer have been marketed in the world? Count
together.

7 emerging therapies that are not limited to cancer

(1) The first "anti-cancer miracle drug" that does not distinguish between tissue sources - Keytruda

High microsatellite instability or mismatch repair geno-deficient (MSI-H/dMMR) cancer cells have more genetic markers than normal cells, known as "microsatellites"
.

They are short, repetitive DNA sequences
.
Normally mismatched DNA is repaired when cells replicate DNA, and cancer cells with a large number of microsatellites may be defective in this function (also known as mismatch repair defect, or dMMR).

MSI-H/dMMR tumors are most common in endometrial, colorectal, and gastrointestinal cancers, and may also occur in patients with
breast, prostate, bladder, and thymic cancers.

In May 2017, the FDA approved pembrolizumab (drug K) for patients with solid tumors with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR), the first time it was approved for an
indication under a biomarker rather than a specific tumor species.

It has also officially created an era of molecular marker-guided pan-cancer treatment from the official level!

In June 2020, Keytruda's second "unlimited cancer" new indication was approved
.
For the treatment of adult and pediatric patients
with unresectable or metastatic solid tumors with a high tissue tumor mutational burden (TMB-H) ≥ 10 mutations/megabases (using FDA-specified tests).
The approval of TMB as a molecular marker means that the broad-spectrum anti-cancer range has been expanded again, and more patients will benefit
.

(2) The world's first targeted drug lalotinib that is not limited to cancer types, which can treat 17 types of cancer

Neurotrophic tyrosine receptor kinase (NTRK) is currently the first mutant gene found and recognized as a co-occurrence of whole cancer, which is found in a variety of tumors, and the incidence rate in common tumors lung cancer and colorectal cancer is less than 5%, but it mostly appears in adult and pediatric solid tumors, including breast analogue secretory carcinoma (MASC), thyroid cancer, colon cancer, lung cancer, pancreatic cancer, and various sarcomas
.

The FDA approved Bayer/Loxo's Larotrectinib (trade name: Vitrakvi)
in November 2018.

On April 13, 2022, larotinib was also approved by the National Medical Products Administration of China and officially marketed
.

The reason why this drug is impressive is that the biggest three points are: First, there is no limit to cancer
.

As long as NTRK fusion is present, 17 cancer types, including breast, colorectal, lung, and thyroid cancer, can be used for both adults and children
.
And for infant fibrosarcoma and thyroid cancer, the effective rate of gastrointestinal stromal tumors can be as high as 100%!

Second, the overall response rate was as high as 75%.

Pooled data from three large clinical trials in patients with TRK fusion carcinoma showed an overall response rate of up to 75% ORR, with 22% of patients in complete response
.

Third, fast and durable response
.
The data showed that the average time to onset of action was only 1.
84 months, and 73% of patients responded for a duration of more than 6 months
.
(One case report showed that a 2-year-old spindle cell sarcoma girl experienced a rapid response and rapid improvement
in symptoms within 24 hours of receiving lalotinib.
) ）

(3) The world's third "cure" anti-cancer drug - entitrutinib

In 2019, the world's third broad-spectrum curative "anti-cancer drug Entrectinib (Rozlytrek, entretinib, RXDX-101) was launched, once again making the broad-spectrum anti-cancer dream of no cancer species, no age limit, and only specific gene mutations into reality
.

On July 29, 2022, China's National Medical Products Administration (NMPA) officially announced that Roche's entretinib capsules (Rozlytrek, Entrectinib, RXDX-101) have been approved for the treatment of neurotrophogomyosin receptor kinase (NTRK) fusion-positive, locally advanced or metastatic solid tumors after initial treatment in adults and children over 12 years old!

It also has a resounding Chinese name - Luo Shengquan?
。

(4) The world's first RET inhibitor - LOXO-292 was approved for marketing

RET protein is a membrane receptor tyrosine kinase, and mutation and fusion of the RET gene can lead to overactivation of the RET signaling pathway, leading to tumor initiation and progression
.

Mutations in the RET gene can cause a variety of tumors, including NSCLC, papillary TC, colorectal cancer, ovarian cancer, pancreatic adenocarcinoma, pleural mesothelioma, gastric cancer, cholangiocarcinoma, etc
.

On May 8, 2020, the FDA approved selpercatinib, also known as LOXO-292, for patients with advanced RET fusion-positive non-small cell lung cancer, RET mutated medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancer
.

Selpercatinib is the first precision therapy
approved specifically for the treatment of cancer patients with RET gene variants.

The latest results show that Selpercatinib is also a veritable broad-spectrum anticancer drug, showing amazing clinical efficacy
for a variety of solid tumors.
This broad-spectrum anti-cancer drug with remarkable efficacy for patients with RET gene fusion will bring new choices and hope
to patients.

In November 2021, Selpercatinib submitted a listing application in China and was accepted and included in the priority review
.

(5) The first highly selective RET inhibitor in China, Pratinib cornering overtaking

In May 2020, Lilly's Selpercatinib topped the world, first being approved
by the FDA.

In September 2020, the world's second RET inhibitor, platinib, was approved for marketing
in the United States.

In March 2021, platinib was approved by the State Food and Drug Administration for marketing in China, which is also the first RET inhibitor approved for marketing in China, and the first to overtake in domestic curves
.

(6) Jemperli, an all-cancer anticancer drug, was launched, and the disease remission time was nearly 3 years

In August 2021, dostarlimab-gxly (Jemperli, dostalimab) was launched, and patients with recurrent mismatch repair defect (dMMR) relapsed or advanced solid tumors in adult patients with prior treatment and no satisfactory alternative options were available;

Jemperli is a humanized anti-PD-1 monoclonal antibody
.

It binds to PD-1 with high affinity, thereby blocking its binding to PD-L1 and PD-L2, relieving PD-1-mediated immunosuppression of T cells and helping the body's immune system fight cancer cells
.

The results showed that dostalimab achieved an excellent response rate of 41.
6% in patients with solid tumors with dMMR, including a complete response rate of more than 9%.

In addition, more than 95.
4% of patients had remissions lasting more than half a year, and the median duration of remission was as long as 34.
7 months, nearly 3 years!

(7) "Pan-cancer" program dabrafenib + trametinib, covering 20 types of adult and pediatric tumors

In June 2022, the FDA accelerated the approval of dabrafenil (Tafinlar) in combination with trametinib (Mekinist) for the treatment of patients with unresectable or metastatic solid tumors with BRAF V600E mutations 6 years of age and older who have progressed after prior treatment and for which there are no satisfactory alternative treatment options
.

This is the world's first and only approved drug combination for BRAF V600E mutant adult and pediatric pantumors, and the first BRAF/MEK inhibitor approved for the treatment of pediatric patients, which is a milestone
.

Clinical research data shows that the total objective response rate is as high as 80%! This means that 8 out of 10 patients have tumors that shrink by more than 30% or even disappear completely!

What's more surprising is that this drug combination has different effects on the 20 types of cancer enrolled in the experiment!

brief summary

Surgical treatment, which began in the early 19th century, achieved the goal of "curing" a small number of
patients.

Radiation therapy, which began at the end of the 19th century, developed into the 50s of the last century, and about one-third of patients were effectively treated
by the action of acting alone or in combination.

Chemotherapy, which began in the early 20th century, further improved the therapeutic effect
of tumors.

At the beginning of the 21st century, the emergence of targeted drugs is a great breakthrough in the field of anti-tumor in the past two or three decades, and nearly half of patients have benefited
from it.

These four traditional treatments are extreme, but they fall far short of the desired treatment goals
.

The confirmation of genotyping and targeted therapy signaling pathways provides new ideas
for targeted therapy of "different diseases and treatment".
The emergence of new pan-cancer drugs has brought new hope and treatment options
to more fortunate patients.

This is an era full of miracles, I believe there will be more anti-cancer "new stars" with no limit to cancer to accelerate "unlocking", so stay tuned!