Patient selection to enhance anti-tumor immunity in cancer patients

A technology for cancer and patients, applied in anti-tumor drugs, immunoglobulins, antibodies, etc.

Pending Publication Date: 2022-03-22
G1 THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] The present invention addresses the problem of patient selection for achieving certain cancer treatment outcomes when administering cyclin-dependent kinase 4 / 6 inhibitors to patients in combination with chemotherapy

Method used

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  • Patient selection to enhance anti-tumor immunity in cancer patients
  • Patient selection to enhance anti-tumor immunity in cancer patients
  • Patient selection to enhance anti-tumor immunity in cancer patients

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0233] This article provides the following implementations:

[0234] 1. A method of selecting a patient or patient population for cancer therapy comprising administering a CDK4 / 6 inhibitor with chemotherapy in a manner that increases the patient's progression-free survival or overall survival, the method comprising:

[0235] (i) determine whether the patient's cancer has a surrounding microenvironment conducive to immune regulation;

[0236] (ii) determine whether the chemotherapy regimen induces an immune-mediated response such as immunogenic cell death, and if both (i) and (ii) are yes, then

[0237] (iii) administering an effective amount of a CDK4 / 6 inhibitor selected from compound I, II, III, IV or V or a pharmaceutically acceptable salt thereof,

[0238]

[0239]

[0240] where R is C(H)X, NX, C(H)Y or C(X) 2 ,

[0241] Wherein X is linear, branched or cyclic C 1 to C 5 Alkyl groups, including methyl, ethyl, propyl, cyclopropyl, isopropyl, butyl, sec-butyl, te...

Embodiment 1

[0459] Example 1. Trelacitinib improves overall survival and progression-free survival in human patients with metastatic triple-negative breast cancer receiving gemcitabine and carboplatin.

[0460] Research design

[0461] A multicenter, randomized, open-label, phase 2 study was developed to investigate once-daily administration of triraxime in combination with gemcitabine (IV, 1000 mg / m2) plus carboplatin (IV, AUC-2) (G / C) therapy Safety, Tolerability, Efficacy and PK (G1T28-04) of Nicilin (IV, 240mg / m2) in patients with metastatic TNBC. Patients were randomly assigned (1:1:1 fashion) to 1 of 3 groups:

[0462] Group 1: G / C therapy (days 1 and 8 of a 21-day cycle);

[0463] Group 2: G / C therapy (Days 1 and 8) plus IV administration of Trecitinib on Days 1 and 8 of a 21-day cycle;

[0464] Group 3: G / C therapy (days 2 and 9) plus IV administration of trecicillib on days 1, 2, 8 and 9 of a 21-day cycle;

[0465] Trelacitinib was administered intravenously prior to GC inf...

Embodiment 2

[0524] Example 2: Ayers immune score analysis

[0525] According to Ayers et al., IFN-γ-related mRNA Profile Predicts Clinical Responseto PD-1 Blockade, J Clin Invest. 2017127 (8) 2930-2940 analysis from participating in the clinical trial described in Example 1 (by Q 2 Solutions (Morrisville, NC) assayed tumor samples from patients to determine their Ayers immune score. Data were processed using RNA Access and subjected to FPKM normalization before log10 transformation and averaging.

[0526] 89 samples were analyzed. Computed signature scores for the IFN-γ signature and the extended immune signature were unimodal in distribution and used median scores to define 'high' and 'low' categories. Figure 8A The distribution of the Ayers IFN-γ signature among the 89 samples tested is shown. Figure 8B The distribution of the Ayers expanded immune signature among the 89 samples tested is shown.

[0527] Based on data obtained in the G1T28-04 clinical trial described in Example 1...

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Abstract

There is provided a method of increasing progression-free lifetime or overall lifetime of a cancer patient, comprising: determining whether the cancer has an ambient microenvironment that facilitates immunomodulation; determining whether the chemotherapy regimen induces immunogenic cell death, and if both are so, administering an effective amount of a CDK4 / 6 inhibitor selected from Compound I, II, III, IV or V or a pharmaceutically acceptable salt thereof wherein the CDK4 / 6 inhibitor is administered prior to administration of chemotherapy or optionally prior to and concurrently with chemotherapy; and wherein the increase in progression-free lifetime or overall lifetime is compared to progression-free lifetime or overall lifetime based on the administration of chemotherapy alone, said comparison being based on evidence available in documents or otherwise disclosed, comparisons during preclinical or clinical trials, or other means accepted by those skilled in the art.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Application 662 / 863,153, filed June 18, 2019, and U.S. Provisional Application 62 / 907,375, filed September 27, 2019; the entire contents of each of said Provisional Applications is by all Purpose incorporated herein by reference. technical field [0003] The present invention is in the field of cancer treatment and provides a method of selecting a patient for a favorable and targeted cancer treatment comprising administering cyclin-dependent kinase (CDK) 4 / CDK4 in combination with chemotherapy based on patient and cancer characteristics as further described herein 6 inhibitors. It has been found that when a CDK4 / 6 inhibitor is administered in combination with chemotherapy to a specific sub-section of cancer patients, this selected patient population exhibits a progression-free survival benefit and / or an overall survival benefit. In some embodiments, this result c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/519A61K39/395
CPCA61K31/519A61K45/06A61K31/7068A61K31/555A61K31/7048G01N2800/52G01N33/574G01N2333/70539C12Q1/485C07K16/2827A61K2039/505A61P35/00A61K2300/00A61K31/5377A61K31/522
Inventor P·J·罗伯茨A·莱J·索伦廷
Owner G1 THERAPEUTICS INC
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