ACR-2316 for Cancer

Recruiting at 16 trial locations

Overseen By Mansoor R Mirza, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Acrivon Therapeutics

Disqualifiers: Brain metastases, Recent therapy, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called ACR-2316 to determine its safety for individuals with certain advanced solid tumors, which form in tissues like organs or muscles. Researchers are testing how the body processes the drug and its potential effects. Participants will receive ACR-2316 every three weeks, with the study focusing on different dosage levels. Those with a solid tumor that has progressed despite prior treatment may find this trial suitable. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot have had systemic therapy or radiation therapy within 2 weeks before starting the study drug.

Is there any evidence suggesting that ACR-2316 is likely to be safe for humans?

Research has shown that ACR-2316 underwent safety testing in early studies. A safety review committee approved patients who received the first two dose levels of ACR-2316, indicating these doses were generally well-tolerated. However, as this is an early-phase trial, complete safety data collection is ongoing. While initial results appear promising, the researchers continue to monitor the treatment for any possible side effects as more information becomes available. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

ACR-2316 is unique because it targets cancer cells with a potentially novel mechanism, distinguishing it from standard chemotherapy and targeted therapies. Researchers are excited about ACR-2316 due to its innovative approach of using a specific active ingredient that may offer improved precision in attacking cancer cells, potentially reducing side effects. Additionally, ACR-2316 is administered in a structured 3-week schedule, which may optimize its effectiveness and improve patient outcomes compared to existing treatments.

What evidence suggests that ACR-2316 might be an effective treatment for cancer?

Research has shown that ACR-2316 holds promise in early studies for treating advanced solid tumors. ACR-2316 targets specific proteins that aid cell division, potentially slowing tumor growth. Early clinical results demonstrated about a 25% reduction in tumor size and spread. In this trial, participants will receive ACR-2316 in either a dose escalation or dose expansion arm, both following a 3-week schedule. These findings suggest that ACR-2316 might help manage certain cancers, warranting further research in clinical trials. ^{4 5 6 7 8}

Are You a Good Fit for This Trial?

Inclusion Criteria

I am mostly active and my doctor thinks I have at least 3 months to live.

Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST v1.1

My condition worsened after my last treatment.

Exclusion Criteria

I haven't had any cancer treatment in the last 2 weeks.

I have brain metastases that cause symptoms.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

ACR-2316 is administered to determine the maximal tolerated dose and recommended Phase 2 dose

9 weeks

Multiple visits for PK testing in each cycle

Dose Expansion

ACR-2316 is administered to further assess safety and pharmacokinetics

9 weeks

Multiple visits for PK testing in each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ACR-2316

How Is the Trial Designed?

Group I: Dose expansion Experimental Treatment 1 Intervention

ACR-2316 will be administered using a 3-week schedule.

Group II: Dose escalation Experimental Treatment 1 Intervention

ACR-2316 will be administered using a 3-week schedule.

Who Is Running the Clinical Trial?

Acrivon Therapeutics

Lead Sponsor

Trials

3

Recruited

520+

Published Research Related to This Trial

AXL, a receptor involved in cancer cell growth and spread, was found to be overexpressed in a significant majority of colorectal cancer (CRC) samples, suggesting its potential as a therapeutic target.

Inhibition of AXL using the drug foretinib significantly reduced tumor growth and spread in a mouse model of CRC, indicating that targeting AXL could be an effective new treatment strategy for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AXL is an oncotarget in human colorectal cancer. Martinelli, E., Martini, G., Cardone, C., et al.[2022]

Aclarubicin (ACR) significantly reduces glioma cell survival and proliferation while increasing apoptosis and DNA damage in glioma cell lines (U87 and U251) at concentrations of 1, 2, and 5 μM.

The mechanism of ACR's action involves the activation of the SIRT1/PI3K/AKT signaling pathway, where overexpression of AKT can reverse ACR's effects, highlighting its potential as a targeted therapy in glioma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retracted Article: Aclarubicin regulates glioma cell growth and DNA damage through the SIRT1/PI3K/AKT signaling pathway. Huo, JF., Chen, XB.[2022]

The study identifies a new mechanism of radioresistance in castration-resistant prostate cancer (CRPC) involving the phosphorylation of the androgen receptor (AR) by Ack1 tyrosine kinase, which leads to increased expression of ATM, a protein that helps cancer cells survive radiation therapy.

The Ack1 inhibitor AIM-100 effectively suppresses this signaling pathway, reducing AR phosphorylation and ATM expression, and shows promise in mitigating the growth of radioresistant CRPC tumors when combined with radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ack1-mediated androgen receptor phosphorylation modulates radiation resistance in castration-resistant prostate cancer. Mahajan, K., Coppola, D., Rawal, B., et al.[2022]

High levels of AXL are linked to resistance against therapies in non-small cell lung cancer (NSCLC) and are associated with DNA damage response, particularly in TP53-deficient cell lines.

The selective AXL inhibitor BGB324 (bemcentinib) combined with ATR inhibition significantly reduced cell proliferation and increased DNA damage in NSCLC and large-cell neuroendocrine carcinoma (LCNEC) cell lines, suggesting a promising new treatment strategy for these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AXL Inhibition Induces DNA Damage and Replication Stress in Non-Small Cell Lung Cancer Cells and Promotes Sensitivity to ATR Inhibitors. Ramkumar, K., Stewart, CA., Cargill, KR., et al.[2022]

AKR1C1 is significantly involved in the proliferation and migration of small-cell lung cancer (SCLC) cells, as demonstrated using the H446 cell line and confirmed in vivo with nude mice.

The study suggests that AKR1C1 could serve as an independent biomarker for assessing prognosis and therapy options in SCLC, highlighting its potential role in cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High expression of AKR1C1 is associated with proliferation and migration of small-cell lung cancer cells. Tian, H., Li, X., Jiang, W., et al.[2022]

Citations

1. aacrjournals.org aacrjournals.org/mct/article/24/10_Supplement/C112/766475/Abstract-C112-ACR-2316-is-a-novel-differentiated

Abstract C112: ACR-2316 is a novel, differentiated, clinical ... Accordingly, ACR-2316 exhibited superior potency in cell viability compared to all benchmark inhibitors, including the WEE1/MYT1 inhibitor SGR- ...

2. ir.acrivon.com ir.acrivon.com/news-releases/news-release-details/acrivon-therapeutics-reports-positive-endometrial-cancer-data

Acrivon Therapeutics Reports Positive Endometrial Cancer ... Presented data at ESMO from the ongoing, registrational-intent, multicenter Phase 2 trial of ACR-368 in patients with high grade endometrial cancer.

3. onclive.com onclive.com/view/lunresertib-and-other-pkmyt1-inhibitors-show-promise-in-gynecologic-malignancies

Lunresertib and Other PKMYT1 Inhibitors Show Promise in ... Another PKMYT1 inhibitor, ACR-2316, which also targets WEE1, is being examined for the treatment of patients with advanced solid tumors in a ...

4. nasdaq.com nasdaq.com/articles/acrivon-therapeutics-presents-findings-acr-2316s-mechanisms-tumor-cell-death-aacr-annual

Acrivon Therapeutics Presents Findings on ACR-2316's ... ACR-2316 has demonstrated initial clinical activity with approximately 25% RECIST tumor shrinkage and reduction of metastatic lesions by the ...

5. quiverquant.com quiverquant.com/news/Acrivon+Therapeutics+Unveils+AP3+Generative+AI+KaiSR+Model+and+Promising+ACR-2316+Preclinical+Data+at+AACR-NCI-EORTC+Conference

Acrivon Therapeutics Unveils AP3 Generative AI KaiSR ... Initial clinical data for ACR-2316 in tumors predicted by the AP3 platform showed promising activity and partial responses during dose ...

6. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/357/759299/Abstract-357-Detailed-mechanistic-understanding-of

Detailed mechanistic understanding of ACR-2316, a novel ... Multiparametric flow cytometry confirmed that ACR-2316 triggers DNA damage, premature mitosis, and S/G2-M cell cycle arrest. CellTiter-Glo and ...

7. ir.acrivon.com ir.acrivon.com/news-releases/news-release-details/acrivon-therapeutics-announces-initial-patient-dosing-phase-1

Acrivon Therapeutics Announces Initial Patient Dosing in ... First patient dosed two quarters ahead of original timelines in Acrivon Phase 1 study to assess safety and tolerability of ACR-2316.

8. ir.acrivon.com ir.acrivon.com/news-releases/news-release-details/acrivon-therapeutics-highlights-its-powerful-generative

Investors & Media Company to report initial clinical data for ACR-2316 in AP3-predicted tumor types later this year; clinical activity and confirmed partial ...