ACR-368 for Ovarian Cancer

Recruiting at 56 trial locations

Overseen By Annette Paulsen

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Acrivon Therapeutics

Must not be taking: Anticoagulants, Steroids

Disqualifiers: Brain metastases, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Until disease progression or unacceptable toxicity

353 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of ACR-368 (also known as Prexasertib or LY-2606368) alone or with a small dose of another drug for individuals with endometrial cancer, which affects the lining of the uterus. Researchers aim to determine if this treatment benefits those whose cancer has spread or worsened after other therapies. Individuals with endometrial cancer that has not improved with previous treatments and who have undergone a tumor biopsy might be suitable for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ACR-368, also known as prexasertib, is being tested for safety in people with ovarian cancer. Studies have found that this drug has been effective for some patients over time, suggesting potential benefits for certain individuals.

Regarding safety, earlier studies examined how well patients tolerate ACR-368. One study focused on women with very difficult-to-treat ovarian cancer, and the results helped researchers understand patient responses to the treatment. Some side effects were reported, which is common with cancer treatments.

The safety of ACR-368 remains under study, but it is encouraging that it has been tested with other cancer patients, providing doctors with valuable insights. Always consult a healthcare provider about the risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ACR-368 for ovarian cancer because it offers a novel approach compared to standard treatments like chemotherapy, surgery, and targeted therapies. ACR-368 is unique because it is being tested with ULDG sensitization, which may enhance its effectiveness by making cancer cells more vulnerable to the treatment. For patients with OncoSignature Positive Tumors, ACR-368 is being evaluated as a monotherapy, potentially simplifying the treatment regimen and reducing side effects. Unlike existing options, this personalized approach targets specific tumor signatures, which could lead to more effective and tailored treatments for ovarian cancer patients.

What evidence suggests that this trial's treatments could be effective for ovarian cancer?

Research has shown that ACR-368, also known as prexasertib, may help treat ovarian cancer. In this trial, participants with OncoSignature Positive Tumors will receive ACR-368 as monotherapy, while those with OncoSignature Negative Tumors or who are OncoSignature Unselected will receive ACR-368 with ULDG sensitization. Studies have found that ACR-368 can work well on its own, providing lasting benefits for some patients. In one study, patients experienced an average period of about 5 months before their cancer worsened. ACR-368 blocks proteins called CHK1/2, which cancer cells use to repair themselves. This makes it harder for the cancer to survive, suggesting it could be effective for certain types of cancer, including ovarian cancer. ^{3 4 5 6 7}

Who Is on the Research Team?

Jung-Min Lee, MD

Principal Investigator

National Cancer Institute (NCI)

Panagiotis Konstantinopoulos, MD

Principal Investigator

Dana-Farber Cancer Institute (DFCI)

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• ACR-368
• Gemcitabine

Trial Overview 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.

How Is the Trial Designed?

Group I: OncoSignature Unselected (All-Comers) Experimental Treatment 2 Interventions

Arm 3: Participants who are OncoSignature Unselected (i.e. they will not require a newly obtained tumor biopsy or OncoSignature testing) will receive ACR-368 with ULDG sensitization. The Phase 2 Study will assess the efficacy and safety of ACR-368 with ULDG sensitization.

Group II: OncoSignature Positive Tumors Experimental Treatment 2 Interventions

ARM 1: Participants with OncoSignature Positive Tumors will enter a Phase 2 Simon 2-Stage Study that will assess the efficacy of ACR-368 as monotherapy.

Group III: OncoSignature Negative Tumors Experimental Treatment 3 Interventions

Arm 2: Participants with OncoSignature Negative Tumors will receive ACR-368 with ULDG sensitization. The Phase 2 Study will assess the efficacy and safety of ACR-368 with ULDG sensitization.

Who Is Running the Clinical Trial?

Acrivon Therapeutics

Lead Sponsor

Trials

3

Recruited

520+

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

Published Research Related to This Trial

In a phase 2 study involving 28 women with BRCA wild-type high-grade serous ovarian carcinoma, prexasertib demonstrated clinical activity, with 29% of patients showing partial responses, indicating its potential efficacy in this difficult-to-treat population.

The treatment was generally tolerable, although it caused significant side effects like neutropenia in 93% of patients, which was mostly transient and resolved without additional support, suggesting that while effective, careful monitoring for adverse effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Lee, JM., Nair, J., Zimmer, A., et al.[2021]

Prexasertib, a CHK1 inhibitor, shows strong antitumor effects in pediatric sarcoma cell lines and mouse models, leading to complete regression in certain tumor types, indicating its potential as an effective treatment option.

The combination of prexasertib with chemotherapy can overcome resistance in various pediatric cancers, suggesting that it may enhance the efficacy of existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Broad Spectrum Activity of the Checkpoint Kinase 1 Inhibitor Prexasertib as a Single Agent or Chemopotentiator Across a Range of Preclinical Pediatric Tumor Models. Lowery, CD., Dowless, M., Renschler, M., et al.[2020]

The EPIK-O/ENGOT-OV61 trial is a phase III study investigating the combination of the PI3K inhibitor alpelisib and the PARP inhibitor olaparib in patients with platinum-resistant high-grade serous ovarian cancer, aiming to improve outcomes for this difficult-to-treat population.

The primary goal of the trial is to assess progression-free survival, with overall survival as a key secondary endpoint, highlighting the potential of this combination therapy to offer a new treatment option for patients without germline BRCA mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EPIK-O/ENGOT-OV61: alpelisib plus olaparib vs cytotoxic chemotherapy in high-grade serous ovarian cancer (phase III study). Konstantinopoulos, PA., Gonzalez-Martin, A., Cruz, FM., et al.[2022]

Prexasertib, a CHK1 inhibitor, shows significant antitumor activity as a standalone treatment in high-grade serous ovarian cancer (HGSOC) models, including those resistant to the PARP inhibitor olaparib.

When combined with olaparib, prexasertib enhances tumor growth inhibition and overcomes resistance mechanisms by inducing DNA damage and compromising homologous recombination repair, making it a promising strategy for treating resistant HGSOC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The CHK1 Inhibitor Prexasertib Exhibits Monotherapy Activity in High-Grade Serous Ovarian Cancer Models and Sensitizes to PARP Inhibition. Parmar, K., Kochupurakkal, BS., Lazaro, JB., et al.[2022]

In a Phase 2 trial involving 169 patients with high-grade serous ovarian cancer, prexasertib showed a 12.1% objective response rate in platinum-resistant patients, indicating some effectiveness in this difficult-to-treat population.

The treatment was associated with common side effects such as thrombocytopenia and neutropenia, but it demonstrated durable activity regardless of BRCA status or previous therapies, highlighting the need for better biomarkers to identify which patients might benefit most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer. Konstantinopoulos, PA., Lee, JM., Gao, B., et al.[2023]

Prexasertib, a novel checkpoint kinase inhibitor, has shown promising efficacy and safety in treating high-grade serous ovarian cancer (HGSOC) in phase II trials, particularly for patients with wild-type BRCA, indicating it could be a valuable treatment option.

Compared to other similar drugs, prexasertib has a better tolerability profile with moderate hematological toxicity, suggesting it may be safer for patients, although further studies are needed to confirm its efficacy and safety in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prexasertib: an investigational checkpoint kinase inhibitor for the treatment of high-grade serous ovarian cancer. Evangelisti, G., Barra, F., Moioli, M., et al.[2021]

In a phase 1 trial involving 30 pediatric patients with recurrent or refractory solid and CNS tumors, prexasertib was administered safely with no dose-limiting toxicities observed, establishing a recommended phase 2 dose of 150 mg/m2.

While the treatment did not result in objective responses, it did lead to stable disease in three patients, indicating some potential for disease control, particularly in specific tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.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). Cash, T., Fox, E., Liu, X., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10673677/

A Phase 2 Study of Prexasertib (LY2606368) in Platinum ... Prexasertib demonstrated durable single agent activity in a subset of patients with recurrent ovarian cancer regardless of clinical characteristics.

2. ir.acrivon.com ir.acrivon.com/node/7761/pdf

Initial Positive Clinical Data for ACR-368 and Pipeline ... “For the first time, we share statistically significant prospective validation of our AP3 patient selection approach via our ACR-368.

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02324-X/fulltext

744P A phase II study of ACR-368 in patients with ovarian ... ACR-368 (prexasertib), a potent, selective CHK1/2 inhibitor, has shown durable single-agent activity at RP2D in patients (pts) with OvCa.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03414047

A Study of Prexasertib (LY2606368) in Platinum-Resistant ... The purpose of this study is to evaluate the efficacy and safety of prexasertib in women with platinum-resistant or refractory recurrent ovarian cancer.

5. nature.com nature.com/articles/s41467-024-47215-6

The CHK1 inhibitor prexasertib in BRCA wild-type platinum ... The median progression-free survival (PFS) was 5 months, with 4 months in cohort 5 (n = 18) and 6 months in cohort 6 (n = 21) (Fig. 2c, d and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36192237/

A Phase 2 study of prexasertib (LY2606368) in platinum ... Prexasertib demonstrated durable single agent activity in a subset of patients with recurrent ovarian cancer regardless of clinical characteristics.

7. gynecologiconcology-online.net gynecologiconcology-online.net/article/S0090-8258(22)01839-X/fulltext

A Phase 2 study of prexasertib (LY2606368) in platinum ... Prexasertib demonstrated durable single agent activity in a subset of patients with recurrent ovarian cancer regardless of clinical ...