715TiP - ARTS-021-1001: Phase I/II study of ARTS-021, a potent, oral administrated, selective CDK2 inhibitor, in advanced or metastatic solid tumors

Background

ARTS-021 is an investigational, reversible, orally administrated CDK2 selective inhibitor that inhibits CDK2 at nanomolar potency and with over 600-fold selectivity against CDK1. Results from pre-clinical research support ARTS-021 as a monotherapy in CCNE1-amplified cancers and in combination with CDK4/6 inhibitors in ER+ breast cancer.

Trial design

This is a first in human, open label, multicenter phase1/2 dose escalation and dose expansion study to evaluate the safety, tolerability, PK, PD, and anti-tumor activity of ARTS-021 1) as a single agent in advanced or metastatic CCNE-1 amplifed solid tumors; 2) in combination with Carboplatin to treat refractory/resistant CCNE-1 amplified ovarian cancer that has failed standard therapies; 3) in combination with endocrine therapy (fulvestrant/letrozole) and CDK4/6 inhibitor(palbociclib/ribociclib/abemaciclib) to treat HR+ HER2- breast cancer patients have failed standard therapies. The phase 1 (dose-escalation) portion will have an accelerated dose escalation followed by a BOIN design. After R2PD is identified, the combination arms will be initiated at one dose level below the monotherapy R2PD. Phase 1 primary endpoints are assessment of safety, tolerability, and pharmacokinetics (PK). The secondary endpoint is preliminary efficacy. Once the RP2D is defined for both monotherapy and in combination, the trial will be advanced into three phase 2 expansion cohorts: monotherapy cohort (basket cohort), combination with Carboplatin (ovarian cohort), and combination with endocrine therapy (fulvestrant/letrozole) + CDK4/6 inhibitor (palbociclib/ribociclib/abemaciclib) (HR+ HER- breast cancer cohort). In addition, a food effect cohort will be included in the monotherapy basket cohort. The phase 2 primary end point is to estimate the anti-tumor efficacy in CCNE1 amplified cancer patients or CDK4/6 inhibitor resistant breast cancer patients. Objective tumor response rate will be measured per RECIST v1.1. The secondary endpoint of phase 2 study will be safety/tolerability. Archival tumor and paired fresh tumor biopsy will be collected throughout the study for exploratory pharmacodynamics (PD) and biomarker evaluation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Allorion Therapeutics, Inc.

Funding

Allorion Therapeutics, Inc.

Disclosure

All authors have declared no conflicts of interest.