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▎The content team editor of WuXi AppTec today, Amgen (Amgen) and Five Prime Therapeutics jointly announced that the two parties have reached an agreement that Amgen will acquire Five Prime for approximately US$1.
9 billion and acquire the company’s innovative tumor Learn pipeline.
The main drug candidate in the Five Prime pipeline is a potential "first-in-class" anti-FGFR2b antibody therapy called bemarituzumab.
It has already obtained positive results in phase 2 clinical trials for the first-line treatment of gastric cancer.
Previously, Zai Lab has reached a cooperation agreement with Five Prime to obtain the development rights of this innovative therapy in Greater China and is responsible for clinical trials of the drug in Greater China.
Stomach cancer is the fifth most common cancer in the world and the third leading cause of cancer deaths.
China is one of the countries with the highest incidence of gastric cancer in the world.
China's population accounts for 20% of the world's population, but the incidence and deaths of gastric cancer account for 44% and 50% of the world.
Moreover, 80% of Chinese gastric cancer patients are already at an advanced stage when they are diagnosed.
The current first-line treatment for advanced gastric cancer is still chemotherapy, but the effect is not satisfactory.
The 5-year survival rate is less than 10%.
Bemarituzumab is a monoclonal antibody against FGFR2b.
It has a dual mechanism of action.
It can not only block the signal transduction of growth factors mediated by FGFR2b by binding to FGFR2b, but also kill cancer cells through antibody-dependent cell-mediated cytotoxicity (ADCC).▲The mechanism of action of bemarituzumab (picture source: Five Prime's official website) In a randomized double-blind, active-controlled phase 2 clinical trial called FIGHt, bemarituzumab combined with chemotherapy, during the progression-free survival (PFS), overall survival The three efficacy endpoints of OS and ORR reached the pre-specified statistical significance when the bilateral α=0.
20.
In terms of prolonging the survival of patients, the combination of bemarituzumab/chemotherapy performed particularly well, reducing the patient's risk of death by 42% compared with chemotherapy (p=0.
027).
In the bemarituzumab/chemotherapy group, the median OS of patients has not yet reached, and the OS of the control group is 12.
9 months.
▲Bemarituzumab's primary and secondary efficacy endpoint data in phase 2 clinical trials (picture source: Five Prime's official website) The success of this innovative FGFR2b antibody therapy obtained by Amgen in clinical trials reflects the power of the concept of precision therapy In phase 2 clinical trials, this therapy is used to treat patients with gastric cancer that highly express FGFR2b and do not express HER2.
The analysis of experimental data shows that the expression level of FGFR2b is correlated with the efficacy of bemarituzumab.
In the history of the development of gastric cancer treatment to precision therapy, the treatment of gastric cancer is relatively simple, no matter what type of patient, basically a similar treatment plan is used.
However, with the advancement of science and the emergence of genetic testing in recent years, scientists have gradually realized that gastric cancer is a very complex disease.
They can be divided into different subtypes according to the different genetic variants they carry, as well as the location of the release and other characteristics of the tumor.
For example, the Cancer Genome Atlas (The Cancer Genome Atlas) research group as early as 2014, according to the molecular biological characteristics of gastric cancer, divided it into 4 subtypes: EBV virus positive subtype (EBV), microsatellite unstable type (MSI), genomic stable type (GS) and chromosomal unstable type (CIN).
In recent years, according to different biomarkers, gastric cancer can also be divided into HER2 gene amplification subtype, MET gene amplification subtype, PD-L1 high expression type and so on.
▲The Cancer Genome Atlas (The Cancer Genome Atlas) research group's classification of gastric cancer (picture source: reference [3]) divides gastric cancer into many different types because, according to the different genetic mutations carried by patients, we can develop Targeted targeted drugs.
These precision therapies may bring better treatment effects to patients of different subtypes than conventional therapies.
Bemarituzumab, a candidate therapy targeting FGFR2b, is an example of this.
In addition to targeting FGF2b, more than one therapy has been approved for HER2-positive gastric cancer.
HER2-positive gastric cancer patients account for about one-fifth of the total number of patients.
Previously, the HER2 monoclonal antibody therapy Herceptin developed by Genentech has been an important choice for the treatment of HER2-positive gastric cancer.
In January this year, the US FDA accelerated the approval of the HER2 targeting antibody conjugate drug Enhertu jointly developed by AstraZeneca and Daiichi Sankyo to expand the scope of application to treat HER2-positive locally advanced or metastatic gastric cancer.
patient.
In Phase 2 clinical trials, Enhertu reduced the risk of death by 41% compared with patients receiving chemotherapy.
Image source: Claudin 18.
2, the current emerging target of 123RF, is a tight junction molecule mainly expressed in stomach and gastric gland tissue.
In China, at least a dozen companies are developing innovative therapies targeting Claudin 18.
2, including not only monoclonal antibodies, but also bispecific antibodies and CAR-T therapies.
The Amgen mentioned today is also developing a bispecific antibody therapy (AMG910) targeting CD3 and Claudin 18.
2. In China, Amgen and BeiGene have jointly submitted a clinical trial application for AMG910, which was accepted by the CDE in July last year.
Immunotherapy is also changing the treatment of gastric cancer.
For patients with gastric cancer with high PD-L1 expression, a variety of immune checkpoint inhibitors have been approved to treat patients after treatment.
For the microsatellite unstable (MSI) subtype, the PD-1 inhibitor Keytruda has been approved by the US FDA for the treatment of any tumor type, including gastric cancer.
As for the first-line treatment of gastric cancer, Bristol-Myers Squibb’s PD-1 inhibitor Opdivo has been used in combination with chemotherapy.
It has already obtained FDA priority review and is expected to be approved in May this year.
If approved, it will be the first immunotherapy-based treatment option for the first-line treatment of gastric cancer.
It is foreseeable that with the further understanding of the molecular biological characteristics of gastric cancer, the classification of this complex cancer will be more detailed.
And more targeted therapies will provide patients with a variety of treatment options, allowing them to choose the most suitable treatment based on the characteristics of their cancer.
We wish the development of these therapies smoothly and benefit gastric cancer patients as soon as possible.
Note: This article is intended to introduce medical and health research, not to recommend treatment options.
If you need guidance on treatment plans, please go to a regular hospital for treatment.
Reference: [1] Amgen To Acquire Five Prime Therapeutics For $1.
9 Billion in Cash.
Retrieved March 4, 2021, from https:// -five-prime-therapeutics-for-$1-9-billion-in-cash[2] A double-blind randomized study of bemarituzumab (bema) plus mFOLFOX6 versus placebo plus mFOLFOX6 as first-line treatment for advanced gastric/gastroesophageal junction cancer (FIGHT).
Retrieved March 4, 2021, from https://investor.
fiveprime.
com/static-files/4a4f2bd6-2f46-4aa1-9bbe-78bdfcba4da2[3] Pellino et al.
, (2019).
Targeted therapies in metastatic gastric cancer: Current knowledge and future perspectives.
World J Gastroenterol.
, doi: 10.
3748/wjg.
v25.
i38.
5773
9 billion and acquire the company’s innovative tumor Learn pipeline.
The main drug candidate in the Five Prime pipeline is a potential "first-in-class" anti-FGFR2b antibody therapy called bemarituzumab.
It has already obtained positive results in phase 2 clinical trials for the first-line treatment of gastric cancer.
Previously, Zai Lab has reached a cooperation agreement with Five Prime to obtain the development rights of this innovative therapy in Greater China and is responsible for clinical trials of the drug in Greater China.
Stomach cancer is the fifth most common cancer in the world and the third leading cause of cancer deaths.
China is one of the countries with the highest incidence of gastric cancer in the world.
China's population accounts for 20% of the world's population, but the incidence and deaths of gastric cancer account for 44% and 50% of the world.
Moreover, 80% of Chinese gastric cancer patients are already at an advanced stage when they are diagnosed.
The current first-line treatment for advanced gastric cancer is still chemotherapy, but the effect is not satisfactory.
The 5-year survival rate is less than 10%.
Bemarituzumab is a monoclonal antibody against FGFR2b.
It has a dual mechanism of action.
It can not only block the signal transduction of growth factors mediated by FGFR2b by binding to FGFR2b, but also kill cancer cells through antibody-dependent cell-mediated cytotoxicity (ADCC).▲The mechanism of action of bemarituzumab (picture source: Five Prime's official website) In a randomized double-blind, active-controlled phase 2 clinical trial called FIGHt, bemarituzumab combined with chemotherapy, during the progression-free survival (PFS), overall survival The three efficacy endpoints of OS and ORR reached the pre-specified statistical significance when the bilateral α=0.
20.
In terms of prolonging the survival of patients, the combination of bemarituzumab/chemotherapy performed particularly well, reducing the patient's risk of death by 42% compared with chemotherapy (p=0.
027).
In the bemarituzumab/chemotherapy group, the median OS of patients has not yet reached, and the OS of the control group is 12.
9 months.
▲Bemarituzumab's primary and secondary efficacy endpoint data in phase 2 clinical trials (picture source: Five Prime's official website) The success of this innovative FGFR2b antibody therapy obtained by Amgen in clinical trials reflects the power of the concept of precision therapy In phase 2 clinical trials, this therapy is used to treat patients with gastric cancer that highly express FGFR2b and do not express HER2.
The analysis of experimental data shows that the expression level of FGFR2b is correlated with the efficacy of bemarituzumab.
In the history of the development of gastric cancer treatment to precision therapy, the treatment of gastric cancer is relatively simple, no matter what type of patient, basically a similar treatment plan is used.
However, with the advancement of science and the emergence of genetic testing in recent years, scientists have gradually realized that gastric cancer is a very complex disease.
They can be divided into different subtypes according to the different genetic variants they carry, as well as the location of the release and other characteristics of the tumor.
For example, the Cancer Genome Atlas (The Cancer Genome Atlas) research group as early as 2014, according to the molecular biological characteristics of gastric cancer, divided it into 4 subtypes: EBV virus positive subtype (EBV), microsatellite unstable type (MSI), genomic stable type (GS) and chromosomal unstable type (CIN).
In recent years, according to different biomarkers, gastric cancer can also be divided into HER2 gene amplification subtype, MET gene amplification subtype, PD-L1 high expression type and so on.
▲The Cancer Genome Atlas (The Cancer Genome Atlas) research group's classification of gastric cancer (picture source: reference [3]) divides gastric cancer into many different types because, according to the different genetic mutations carried by patients, we can develop Targeted targeted drugs.
These precision therapies may bring better treatment effects to patients of different subtypes than conventional therapies.
Bemarituzumab, a candidate therapy targeting FGFR2b, is an example of this.
In addition to targeting FGF2b, more than one therapy has been approved for HER2-positive gastric cancer.
HER2-positive gastric cancer patients account for about one-fifth of the total number of patients.
Previously, the HER2 monoclonal antibody therapy Herceptin developed by Genentech has been an important choice for the treatment of HER2-positive gastric cancer.
In January this year, the US FDA accelerated the approval of the HER2 targeting antibody conjugate drug Enhertu jointly developed by AstraZeneca and Daiichi Sankyo to expand the scope of application to treat HER2-positive locally advanced or metastatic gastric cancer.
patient.
In Phase 2 clinical trials, Enhertu reduced the risk of death by 41% compared with patients receiving chemotherapy.
Image source: Claudin 18.
2, the current emerging target of 123RF, is a tight junction molecule mainly expressed in stomach and gastric gland tissue.
In China, at least a dozen companies are developing innovative therapies targeting Claudin 18.
2, including not only monoclonal antibodies, but also bispecific antibodies and CAR-T therapies.
The Amgen mentioned today is also developing a bispecific antibody therapy (AMG910) targeting CD3 and Claudin 18.
2. In China, Amgen and BeiGene have jointly submitted a clinical trial application for AMG910, which was accepted by the CDE in July last year.
Immunotherapy is also changing the treatment of gastric cancer.
For patients with gastric cancer with high PD-L1 expression, a variety of immune checkpoint inhibitors have been approved to treat patients after treatment.
For the microsatellite unstable (MSI) subtype, the PD-1 inhibitor Keytruda has been approved by the US FDA for the treatment of any tumor type, including gastric cancer.
As for the first-line treatment of gastric cancer, Bristol-Myers Squibb’s PD-1 inhibitor Opdivo has been used in combination with chemotherapy.
It has already obtained FDA priority review and is expected to be approved in May this year.
If approved, it will be the first immunotherapy-based treatment option for the first-line treatment of gastric cancer.
It is foreseeable that with the further understanding of the molecular biological characteristics of gastric cancer, the classification of this complex cancer will be more detailed.
And more targeted therapies will provide patients with a variety of treatment options, allowing them to choose the most suitable treatment based on the characteristics of their cancer.
We wish the development of these therapies smoothly and benefit gastric cancer patients as soon as possible.
Note: This article is intended to introduce medical and health research, not to recommend treatment options.
If you need guidance on treatment plans, please go to a regular hospital for treatment.
Reference: [1] Amgen To Acquire Five Prime Therapeutics For $1.
9 Billion in Cash.
Retrieved March 4, 2021, from https:// -five-prime-therapeutics-for-$1-9-billion-in-cash[2] A double-blind randomized study of bemarituzumab (bema) plus mFOLFOX6 versus placebo plus mFOLFOX6 as first-line treatment for advanced gastric/gastroesophageal junction cancer (FIGHT).
Retrieved March 4, 2021, from https://investor.
fiveprime.
com/static-files/4a4f2bd6-2f46-4aa1-9bbe-78bdfcba4da2[3] Pellino et al.
, (2019).
Targeted therapies in metastatic gastric cancer: Current knowledge and future perspectives.
World J Gastroenterol.
, doi: 10.
3748/wjg.
v25.
i38.
5773
