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2021 American Society of Clinical Oncology: Update performance of multiple lung cancer targeted drugs...

 Last Update: 2021-06-22
 Source: Internet
 Author: User

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Lung cancer is the cancer with the highest morbidity and mortality, accounting for 18% of all cancer deaths

▌MET exon 14 jumping mutant lung cancer

At present, the five-year survival rate of lung cancer is less than 20%, and the prognosis of patients with metastatic non-small cell lung cancer (NSCLC) is worse, and MET exon 14 skipping mutations occur in 3%-4% of metastatic NSCLC cases
.

In May last year, Capmatinib was approved by the FDA for the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) patients with skipping mutations in exon 14 of MET, including first-line and subsequent-line treatments
.

This is the first and currently only targeted drug for advanced NSCLC with specific mutations approved by the FDA
.

At this ASCO conference, the test data of the MET inhibitor Capmatinib (Tabrecta) was updated
.

The results show that:

·In the newly treated and treated patients, the median overall survival (OS) of the capmatinib treatment group was 20.
8 months and 13.
6 months, respectively
.

·The overall response rate (ORR) of newly treated and treated patients were 67.
9% and 51.
6%, respectively; the median duration of response (DOR) was 12.
6 months and 9.
7 months, respectively
.

In the future, Capmatinib can be used as a first-line and multi-line therapy to target NSCLC patients with METex14 and prolong the survival period of patients
.

▌EGFR "niche" mutant lung cancer

Non-small cell lung cancer accounts for 85% of all lung cancers, and about one-third of NSCLC patients have EGFR mutations
.
The EGFR exon 20 insertion mutation accounts for 4%-12% of all EGFR mutations and is the third most common type of mutation
.

EGFR exon 20 mutations are not sensitive to chemotherapy and EGFR-TKIs, and the treatment is difficult and the prognosis is poor
.
However, in response to this mutation, innovative targeted drugs ushered in a wave of craze
.

Last month, the EGFR/MET bispecific antibody Amivantamab (Rybrevant) was approved by the FDA for the treatment of adult NSCLC patients with EGFR exon 20 insertion mutations
.

▌Oral EGFR-TK: Mobocertinib

Mobocertinib (TAK-788) is an oral small molecule tyrosine kinase inhibitor (TKI) and the first oral therapy specifically designed to selectively target EGFR exon 20 insertion mutations.
It is expected to be approved in October this year Listed
.

The previously published data shows:

Among 114 NSCLC patients with an insertion mutation in exon 20 of the EGFR gene, the ORR of the Mobocertinib treatment group was 28%, and the disease control rate (DCR) was 78%; the median duration of remission reached 17.
5 months, and one patient was completely Ease
.

In the EXCLAIM study cohort, the median treatment time was 6.
5 months, the ORR of the Mobocertinib treatment group was 25%, and the DCR was 78%; the median progression-free survival (PFS) was 7.
3 months
.

Among them, the subgroup analysis showed that no matter whether the patients received EGFR-TKI treatment or immunotherapy, clinical benefits were observed
.

▌HER inhibitor: Poziotinib

Poziotinib is an innovative broad-spectrum HER inhibitor that can irreversibly block the signal transmission of HER family tyrosine kinase receptors, thereby inhibiting tumor cell proliferation
.

At the ESMOTAT virtual conference in 2021, Poziotinib has achieved positive results in the treatment of lung cancer patients with EGFR gene mutations
.

It is worth noting that at this ASCO conference, Poziotinib has updated the data in lung cancer with brain metastases:

Among lung cancer patients with brain metastases (n=36), ORR was 22.
2% and DCR was 88.
9%
.
In each of the three cohorts, 1 patient achieved complete intracranial remission
.

This indicates that Poziotinib is not only effective for patients with EGFR and HER2 insertion mutations, but also has the potential to treat lung cancer patients with brain metastases
.

▌Oral EGFR-TKI: CLN-081 (Cullinan)

CLN-081 (formerly known as TAS6417) is an oral EGFR-TKI that can selectively target cells expressing EGFR mutations
.
In addition to EGFR exon 20 mutations, rare mutations such as EGFR exon 18 and 21 may also be targeted
.

The results of a clinical study announced at the ASCO meeting showed:

Among 42 patients with evaluable efficacy, the ORR of the CLN-081 treatment group was 50%, and the DCR was 64%
.
At the sixth week of treatment, 76% of patients showed some degree of tumor shrinkage
.

Among them, two of the patients with the longest remission time were patients who failed both Mobocertinib and Poziotinib
.

▌EGFR/HER2 inhibitor: DZD9008 (Dizal)

DZD9008 is a small molecule compound targeting EGFR/HER2 exon 20 mutation and is currently under clinical research
.

In the international multi-center Phase 1, Phase 2 and China Phase 1 clinical trials, 97 patients with EGFR/HER2 mutant NSCLC were enrolled, and 42.
9% of them had brain metastases
.

Preliminary data show that the best tolerated dose (MTD) of DZD9008 is 400mg
.

The results announced at the ASCO meeting showed:

When the dose is ≥100mg, some patients have remission
.
When the dose was 300 mg, the objective remission rate of the treatment group was 48.
4% (15/31), and the disease control rate was 90.
3% (28/31)
.

At the time of the data cutoff, the average treatment time was 100 days
.
The longest remission lasted more than 6 months, and 18 of the 22 remission patients were still in continuous remission
.

Moreover, anti-tumor activity can be observed in patients with different mutation subtypes and brain metastases
.

In addition, drugs targeting EGFR/HER2 exon 20 mutations include BDTX-189 (Black Diamond), which is worth looking forward to
.

Although this type of gene mutation is relatively rare, its proportion is still not a minority compared to the base number of lung cancer patients in China
.
In the future, more drugs will be approved for EGFR exon 20 mutations, benefiting the majority of lung cancer patients
.

Reference materials:

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