ACR-368

Shows activity

Also known as:

Prexasertib

Cancer types include:

cervical cancer head and neck cancer uterine cancer

TrialFetch AI Analysis

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Overview

ACR-368 (prexasertib) is an investigational cancer drug studied alone and in combination with chemotherapy. Human phase 1/2 and phase 2 results are available, but the reported studies are small or single-arm, so response rates do not establish how it compares with other treatments. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

Prexasertib inhibits checkpoint kinases CHK1 and CHK2, which help cells respond to DNA damage and replication stress. Inhibiting these checkpoints can prevent damaged cancer cells from completing DNA repair before division. (ascopubs.org)

Efficacy

Ovarian cancer: In a phase 2 study of 169 patients with platinum-resistant or platinum-refractory recurrent disease, the objective response rate (ORR) was 12.1% in the platinum-resistant cohorts and 6.9% in the refractory cohort. A separate phase 2 study in BRCA-wild-type, platinum-resistant high-grade serous ovarian cancer reported responses in 12 of 39 evaluable patients (30.8%); its primary endpoint could not be fully evaluated because the trial stopped early. (pubmed.ncbi.nlm.nih.gov)
Endometrial cancer: Preliminary, company-supplied data presented at a 2026 scientific meeting reported an ORR of 39% among 31 patients selected by an investigational OncoSignature test to receive ACR-368 alone. The presentation included unconfirmed responses; these findings need further evaluation. (sec.gov)
Desmoplastic small round cell tumor: In a 19-patient phase 1/2 study combining ACR-368 with irinotecan, the ORR was 32% across all doses. The combination study cannot isolate ACR-368’s contribution. (pubmed.ncbi.nlm.nih.gov)

Safety

Blood-cell suppression is a prominent risk. In the 49-patient ovarian cancer study, grade 3–4 neutropenia occurred in 85%, thrombocytopenia in 40%, and febrile neutropenia in 12%. Fatigue and nausea were also commonly reported in the larger ovarian study. In the preliminary endometrial-cancer presentation, grade 3–4 anemia, neutropenia, and thrombocytopenia occurred in 27%, 25%, and 22%, respectively, among 40 patients receiving ACR-368 alone. (aacrjournals.org)

Active trials using ACR-368

Found 2 active trials using this drug:

A Phase II Study of ACR-368 and Low Dose Gemcitabine Combination Therapy in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

Sponsor: H. Lee Moffitt Cancer Center and Research Institute (other) Phase: 2 Start date: Sept. 25, 2024

TrialFetch AI summary: This single-arm study enrolls patients with measurable recurrent or metastatic head and neck squamous cell carcinoma and ECOG performance status 0–1, generally after PD-1/PD-L1 therapy, in separate p16/HPV-positive and -negative cohorts. Patients receive low-dose gemcitabine plus prexasertib (ACR-368), an investigational CHK1/CHK2 inhibitor that disrupts the response to DNA damage and replication stress.

ClinicalTrials.gov ID: NCT06597565

A Phase 2 Study of ACR-368 Therapy in Subjects With Endometrial Cancer

Sponsor: Acrivon Therapeutics (industry) Phase: 2 Start date: Aug. 29, 2022

TrialFetch AI summary: Adults with high-grade metastatic endometrial cancer progressing after platinum chemotherapy and anti-PD-(L)1 therapy receive the CHK1/CHK2 inhibitor ACR-368 (prexasertib) alone if OncoSignature-positive, or with ultra-low-dose gemcitabine if OncoSignature-negative or unselected. Gemcitabine is used to sensitize tumors to ACR-368.

ClinicalTrials.gov ID: NCT05548296