Higher activity than existing targeted drugs, new expectations for ovarian cancer, fallopian tube cancer and peritoneal cancer

For a long time in global clinical trials, we have been studying targeted drugs for tumor driver genes, such as directly anchoring EGFR or ALK gene mutations, and inhibiting tumors through the combination of drugs with proteins translated by the mutant genes.

If we follow this line of thinking, it will be difficult for many tumors to have targeted drugs.

For example, the driver genes of malignant tumors such as ovarian cancer, fallopian tube cancer and peritoneal cancer are relatively scattered, and most of the genes are not suitable as drug targets, which brings great difficulties to the development of targeted drugs.

BRCA gene mutations and targeted drugs BRCA1 and BRCA2 genes are genes that affect the risk of breast cancer and ovarian cancer.
If you carry these two gene mutations, you are prone to breast and ovarian cancer.

And the patients are often very young.

However, the BRCA gene is a gene that inhibits the occurrence of cancer.
Its main function is to repair the gene and avoid errors in gene replication.

So how to study drugs for these two genes? This is the principle of PARP inhibitors.

Figure 1 Carrying BRCA gene mutations are more likely to develop tumors.
As shown in the figure above, if the patient is born with BRCA gene mutations (germ cell gene mutations).

Then BRCA gene mutations are often the cause of ovarian cancer and other tumors, that is, an inactivated BRCA gene is born.
In the acquired environment, another normal BRCA gene in certain cells also loses its function, so these cells lose their function.
Carcinogenesis has occurred and a tumor has formed.

This is also known as the doctrine of the second hit.

Therefore, for tumors caused by BRCA gene mutations, such tumors are defective in gene repair.

It can only rely on another gene repair pathway called PARP.

Figure 2 The mechanism of action of PARP drugs is shown in the figure above.
We use drugs to inhibit and block the PARP pathway, so that the two gene repair pathways of tumor cells are gone, and they collapse and die.

But normal cells still have a BRCA gene at work, so it will not be affected.

IMP4297, a more confident targeted drug, currently has a variety of PARP inhibitors on the market in my country, such as olaparib, niraparib, etc.
, and these drugs are also included in medical insurance.

Greatly reduce the economic burden of patients.

In some key clinical trials, the PARP inhibitors currently on the market can greatly extend the survival time of patients and bring great benefits to patients.

IMP4297 is a new type of PARP inhibitor.

It can inhibit PARP1 and PARP2.
In animal model experiments, it has been proved that its inhibitory effect is 20 times higher than that of olaparib.

But animal tests are only animal tests after all, and it is still necessary to verify its anti-cancer activity in human tests.

Two phase I clinical trials have been reported to confirm the safety and effectiveness of IM4297 in patients with ovarian cancer, breast cancer, prostate cancer and other solid tumors in China and Australia.

Figure 3 IMP4297 clinical study data.
Among 15 patients with BRCA gene-positive mutations with measurable lesions, the treatment response rate was 33%, the disease control rate was 80%, and the treatment response of 4 BRCA-positive mutation platinum-based chemotherapy-sensitive ovarian cancers The rate is 75%, and the disease control rate is 100%.

A patient with urothelial cancer with a somatic mutation in the BRCA gene shrank 76%.

That is, if it is not a genetic mutation of the BRCA gene, but only a BRCA gene mutation that the cancer cell later appears, IM4297 is also effective.

In short, the current clinical data show that IM4297 has a wider treatment range and better safety.

Now, have the opportunity to use this drug for free.
Recently, the Phase II clinical study of IM4297 has been approved by the National Medical Products Administration (Lot Number: 2017L00044).
This is a multi-center, open, single-arm, Non-randomized clinical research.

That is, all selected patients will use IM4297 instead of the control group's drugs or placebo.

If there is a measurable tumor lesion with non-mucinous epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with BRCA1 or BRCA2 gene mutations, you can register.

(If the follow-up inspection can meet the requirements of other clinical studies, and you agree to participate in the study, you may successfully participate in this clinical trial.

) You do not need to pay for the study drug or the testing, examination or medical treatment required by this study.

You can sign up by choosing "free medication" in the cancer app, or you can search for the "Global Clinical Trials" applet on WeChat to sign up.

Reference source for global clinical trials https://ascopubs.
org/doi/abs/10.
1200/JCO.
2019.
37.
15_suppl.
3059