ACR-368 for Ovarian Cancer

Recruiting at 68 trial locations

Overseen By Monica Phadnis

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 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)

Compensation: Varies

Number of Visits: 1

Duration: Until disease progression or unacceptable toxicity

390 Participants Needed

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. ^{1 2 3 4 5}

What 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. ^{1 2 3 5 6}

What 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. ^{1 2 3 5 7}

Research Team

Jung-Min Lee, MD

Principal Investigator

National Cancer Institute (NCI)

Jonathan Rosenberg, MD

Principal Investigator

Memorial Sloan-Kettering Cancer Center (MSKCC)

Eligibility 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.

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

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

Treatment Details

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.

Participant Groups

Group I: OncoSignature Positive Tumors Experimental Treatment 2 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 Negative Experimental Treatment 3 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).

Who Is Running the Clinical Trial?

Acrivon Therapeutics

Lead Sponsor

Trials

3

Recruited

520+

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

Findings from Research

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 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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Prexasertib: an investigational checkpoint kinase inhibitor for the treatment of high-grade serous ovarian cancer. [2021]

2. England 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. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

EPIK-O/ENGOT-OV61: alpelisib plus olaparib vs cytotoxic chemotherapy in high-grade serous ovarian cancer (phase III study). [2022]

5. United States 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). [2022]

6. United States pubmed.ncbi.nlm.nih.gov

The CHK1 Inhibitor Prexasertib Exhibits Monotherapy Activity in High-Grade Serous Ovarian Cancer Models and Sensitizes to PARP Inhibition. [2022]

7. United States 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. [2020]