ACR-368 for Ovarian Cancer
Recruiting in Palo Alto (17 mi)
+69 other locations
Overseen ByJung-Min Lee, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Acrivon Therapeutics
Must not be taking: Anticoagulants, Steroids
Disqualifiers: Brain metastases, HIV, Hepatitis, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial tests a new drug, ACR-368, alone or with a small dose of another drug, gemcitabine, in patients whose cancers don't respond to standard treatments. A special test helps decide which treatment might work best for each patient. Gemcitabine has been used with other drugs for various cancers, including pancreatic, lung, ovarian, and breast cancers.
Will I have to stop taking my current medications?
The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that participants should not have had systemic therapy or radiation therapy within 2 weeks prior to the first dose of the study drug, which might imply a need to pause certain treatments. Please consult with the trial coordinators for specific guidance.
What data supports the effectiveness of the drug ACR-368 (Prexasertib) for ovarian cancer?
Research shows that Prexasertib, a part of ACR-368, has shown promising results in early trials for treating high-grade serous ovarian cancer, especially in patients without BRCA mutations. It has demonstrated clinical activity and a better tolerability profile compared to similar drugs.
12345What safety data is available for ACR-368 (Prexasertib) in humans?
Prexasertib (also known as ACR-368) has been tested in clinical trials for ovarian cancer and other solid tumors, showing a moderate safety profile with some hematological toxicity (effects on blood cells). It has been generally well-tolerated in phase I and II trials, but further studies are needed to confirm its safety when used in combination with other treatments.
12356What makes the drug ACR-368 (Prexasertib) unique for treating ovarian cancer?
ACR-368 (Prexasertib) is unique because it is a novel checkpoint kinase inhibitor that targets cell cycle checkpoints, specifically CHK1 and CHK2, which can help improve clinical response in high-grade serous ovarian cancer, especially in cases resistant to standard platinum-based chemotherapy.
12357Eligibility Criteria
This trial is for adults with certain advanced cancers (ovarian, endometrial adenocarcinoma, or urothelial carcinoma) that have worsened after treatment. They must be able to consent, provide tumor samples, expect to live more than 3 months, have good organ function and performance status, and recovered from previous treatments' side effects.Inclusion Criteria
Participant must have an estimated life expectancy of longer than 3 months.
My organs are functioning well.
I have recovered from side effects of previous treatments, except for some conditions.
+8 more
Exclusion Criteria
I have an uncontrolled HIV, hepatitis B, or hepatitis C infection.
My cancer type is not excluded by the study.
I have previously taken a CHK1 inhibitor medication.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive ACR-368 as monotherapy or in combination with ultralow dose gemcitabine based on OncoSignature status
Until disease progression or unacceptable toxicity
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 2 years
Pharmacokinetic Testing
Limited PK testing of ACR-368 in combination with ULDG in Arm 2 and monotherapy in Arm 1
First cycle
Day 1 and Day 15 of first cycle
Participant Groups
The study tests ACR-368 alone or with very low doses of Gemcitabine in patients selected by the OncoSignature test. It's an early-phase trial assessing how well these treatments work and their safety in participants with specific resistant cancers.
2Treatment groups
Experimental Treatment
Group I: OncoSignature Positive TumorsExperimental Treatment2 Interventions
In Arm 1, participants with an OncoSignature Positive test will enter a Phase 2 Simon 2-Stage Study that will assess the efficacy of ACR-368 as monotherapy in each of the 3 cohorts of participants (ovarian, endometrial, and urothelial).
Group II: OncoSignature NegativeExperimental Treatment3 Interventions
In Arm 2, participants with an OncoSignature Negative will receive the combination of ACR-368 and ultralow Dose Gemcitabine (ULDG). The Phase 1b/2 portion will only enroll participants with OncoSignature Negative tumors. Unevaluable tumors will not be able to participate. A Phase 1b Study will assess the safety of the combination of ACR-368 and escalating doses of ULDG in participants with any of the 3 tumor types (ovarian, endometrial, and urothelial). The Phase 1b Study will determine the recommended Phase 2 dose (RP2D) of ULDG. A Phase 2 Exploratory Study will assess the efficacy and safety of the combination of ACR-368 and the RP2D of ULDG in each of the 3 cohorts of participants (ovarian, endometrial, and urothelial).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mount Sinai HospitalNew York, NY
FirstHealth of the CarolinasPinehurst, NC
University of Texas Southwestern Medical CenterDallas, TX
Dana Farber Cancer InstituteBoston, MA
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Acrivon TherapeuticsLead Sponsor
GOG FoundationCollaborator
References
Prexasertib: an investigational checkpoint kinase inhibitor for the treatment of high-grade serous ovarian cancer. [2021]Introduction Patients with high-grade serous ovarian cancer (HGSOC) have a poor prognosis, and current chemotherapy regimens for treating advanced disease are far from satisfactory. Prexasertib (LY2606368) is a novel checkpoint kinase inhibitor (CHK) under investigation for the treatment of HGSOC. Data from a recent phase II trial showed promising efficacy and safety results for treating wild-type BRCA HGSOC. Areas covered This article reviews the available data on the pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of prexasertib in the treatment of HGSOC. Expert opinion Until now, prexasertib demonstrated clinical activity in phase I and II clinical trial for treating wild-type BRCA HGSOC, whereas its promising efficacy as monotherapy and combined with olaparib in BRCA-mutated HGSOC has been preliminary evidenced only in phase I studies. Compared to other drugs of the same class, prexasertib showed a better tolerability profile, causing moderate hematological toxicity. Further studies are needed to confirm efficacy and safety profiles of prexasertib in combined regimens. New early clinical trials may investigate prexasertib administered with programmed cell death ligand 1 (PD-L1) and PI3 K inhibitors due to the preclinical evidence of a synergic action.
Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type recurrent high-grade serous ovarian cancer: a first-in-class proof-of-concept phase 2 study. [2021]High-grade serous ovarian carcinoma is characterised by TP53 mutations, DNA repair defects, and genomic instability. We hypothesised that prexasertib (LY2606368), a cell cycle checkpoint kinase 1 and 2 inhibitor, would be active in BRCA wild-type disease.
A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer. [2023]High-grade serous ovarian cancer, the most frequent type of ovarian cancer, has a poor prognosis and novel treatments are needed for patients with platinum resistant/refractory disease. New therapeutic strategies targeting cell cycle checkpoints, including CHK1 inhibition with prexasertib, may help improve clinical response and overcome resistance.
EPIK-O/ENGOT-OV61: alpelisib plus olaparib vs cytotoxic chemotherapy in high-grade serous ovarian cancer (phase III study). [2022]Patients with platinum-resistant or -refractory high-grade serous ovarian cancer (HGSOC) have a poor prognosis, and their management represents a substantial unmet medical need. Preclinical data and results from a phase Ib trial demonstrated the efficacy and tolerability of the combination of the α-specific phosphatidylinositol-3-kinase (PI3K) inhibitor alpelisib plus the poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor olaparib in platinum-resistant, non-BRCA-mutated ovarian cancer. Here, we describe the study design and rationale for the phase III, multicenter, open-label, randomized, active-controlled EPIK-O/ENGOT-OV61 trial investigating alpelisib in combination with olaparib compared with standard-of-care chemotherapy in patients with platinum-resistant or -refractory HGSOC with no germline BRCA mutation. Progression-free survival (blinded independent review committee) is the primary end point. Overall survival is a key secondary end point. Clinical Trial Registration:: NCT04729387 (ClinicalTrials.gov).
A phase 1 study of prexasertib (LY2606368), a CHK1/2 inhibitor, in pediatric patients with recurrent or refractory solid tumors, including CNS tumors: A report from the Children's Oncology Group Pediatric Early Phase Clinical Trials Network (ADVL1515). [2022]Prexasertib (LY2606368) is a novel, second-generation, selective dual inhibitor of checkpoint kinase proteins 1 (CHK1) and 2 (CHK2). We conducted a phase 1 trial of prexasertib to estimate the maximum-tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), to define and describe the toxicities, and to characterize the pharmacokinetics (PK) of prexasertib in pediatric patients with recurrent or refractory solid and central nervous system (CNS) tumors.
The CHK1 Inhibitor Prexasertib Exhibits Monotherapy Activity in High-Grade Serous Ovarian Cancer Models and Sensitizes to PARP Inhibition. [2022]PARP inhibitors are approved for the treatment of high-grade serous ovarian cancers (HGSOC). Therapeutic resistance, resulting from restoration of homologous recombination (HR) repair or replication fork stabilization, is a pressing clinical problem. We assessed the activity of prexasertib, a checkpoint kinase 1 (CHK1) inhibitor known to cause replication catastrophe, as monotherapy and in combination with the PARP inhibitor olaparib in preclinical models of HGSOC, including those with acquired PARP inhibitor resistance.
Broad Spectrum Activity of the Checkpoint Kinase 1 Inhibitor Prexasertib as a Single Agent or Chemopotentiator Across a Range of Preclinical Pediatric Tumor Models. [2020]Checkpoint kinase 1 (CHK1) inhibitors potentiate the DNA-damaging effects of cytotoxic therapies and/or promote elevated levels of replication stress, leading to tumor cell death. Prexasertib (LY2606368) is a CHK1 small-molecule inhibitor under clinical evaluation in multiple adult and pediatric cancers. In this study, prexasertib was tested in a large panel of preclinical models of pediatric solid malignancies alone or in combination with chemotherapy.