The latest data disclosure!

ESMO is one of the most important global conferences that professionals in the oncology field pay attention to.

The content of the report on the target CDK1

The topic of the ESMO conference in 2021, the search for content related to CDK1, mainly contains two themes, but the protagonists of the two themes are the WEE1 inhibitor ZN-c3 developed by Zentails, and WEE1 is the upstream target of CDK1

In terms of pharmacodynamics, the use of ZN-c3 (80mg/kg qdx3) to treat tumor-bearing mice showed significant inhibition of phosphorylation of CDK1 in tumors; in phase I clinical trials, 23 subjects (300 mg qd or higher dose) for skin biopsy, 18/23 patients (78.

From the plasma test data, there is a significant correlation between drug exposure and WEE1 inhibition.

In terms of dose escalation of combination drugs, it is mainly the phase Ib dose escalation study of ZN-c3 combined with chemotherapy in the treatment of platinum-resistant or refractory ovarian cancer, peritoneal cancer or fallopian tube cancer.

Table 1.

The content of the report on the target CDK4/6

The topics of the ESMO conference in 2021, search for content related to CDK4/6, a total of 17 reports are related to it, and further screening is carried out, which specifically reflects the reports and abstracts of the listed varieties.

➢ Abemaciclib related reports (153P)

In a large study, a total of 5637 subjects were recruited, 43.

➢ palbociclib & ribociclib related reports (256P)

A study included 36 patients with a median age of 59 years.

➢ palbociclib related reports (240P)

A study recruited 191 patients, 140 were first-line patients, with a median age of 57.

Table 2.

Contents of the report on target CDK7

The topics of the ESMO conference in 2021, search for content related to CDK7, there are a total of 5 reports related to it, and further screening, the report and summary key results that specifically reflect the clinical varieties are as follows

➢ SY-5609(13P+14P)

According to reports, SY-5609 is an effective and selective CDK7 inhibitor for phase I clinical studies of patients with advanced solid tumors (including ovarian cancer).

In another study, in the PDAC-PDX model of RAS mutation, it was well tolerated and subsided 2 weeks after stopping the drug

In another study, 51 patients were enrolled, and the two QD administration methods, 4mg/d or 5mg/d, passed the toxicity evaluation, and they are still in the climbing stage

➢ CT7001 (samuraciclib)

In one study, 31 HR+BC subjects who received a standard dose combination of fulvestrant and samuraciclib were enrolled.

In another study, 33 people were recruited for the dose escalation trial, divided into 5 groups (120mg OD, 240mg OD, 360mg OD, 480mg OD, 180mg BID); 11 patients in the tumor biopsy cohort were administered for pharmacodynamic evaluation; 15 patients were enrolled in food and drug related; 23 patients were enrolled in the extended cohort; plasma exposure reached a steady state within 8-15 days and increased in proportion; the most common adverse reactions were nausea, vomiting, and diarrhea
.
The overall data shows that food has no significant effect on the efficacy of the drug
.
Twenty patients with TNBC can be evaluated by RECIST, 12/20 are in stable condition at FPBS, and 3 patients have been treated for more than 1 year
.

Table 3.
1 2021 ESMO-related CDK7 report topics

The content of the report on the target CDK12

2021 ESMO conference topics, search for content related to CDK12, a total of 10 reports related to them, further screening, statistics found that most of the CDK12-related subjects are accompanied by CDK12 mutations and CDK12 rearrangements.
The report topics are summarized as follows
.

Table 4.
1 2021 ESMO-related CDK12 report topics

Summarize

The above is the latest ESMO clinical data disclosure on CDK family inhibitors in 2021, which are summarized as follows:

1) The clinical data is still dominated by CDK4/6 inhibitors, with the most disclosed data and information;

2) CDK family of other targets, the fastest development progress is the CDK7 inhibitor, and the existing varieties have progressed to phase II clinical, and its two mechanisms of action have great potential;

3) CDK1 mainly takes the upstream target WEE1 as the development direction, and the clinical varieties are highly active;

4) CDK12 is currently receiving high attention, and no clinical representative varieties have been published yet
.

references:

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For the full text, please refer to ESMO official website information https://