ACR-2316 for Cancer

Recruiting at 7 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

Trial Summary

What is the purpose of this trial?

This is a first in-human, Open-label Phase 1 study to assess the safety of ACR-2316 for the treatment of subjects with specific, histologically confirmed, locally advanced, recurrent or metastatic solid tumors.

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.

What makes the drug ACR-2316 unique for cancer treatment?

ACR-2316 is unique because it is an anthracycline anti-tumor agent that impedes cancer cell survival and promotes DNA damage through the SIRT1/PI3K/AKT signaling pathway, which is different from other treatments that may not target this specific pathway. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

Interventions

• ACR-2316

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

Ack1-mediated androgen receptor phosphorylation modulates radiation resistance in castration-resistant prostate cancer. [2022]

2. United States 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. [2022]

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

AXL is an oncotarget in human colorectal cancer. [2022]

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

Retracted Article: Aclarubicin regulates glioma cell growth and DNA damage through the SIRT1/PI3K/AKT signaling pathway.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

5. New Zealand pubmed.ncbi.nlm.nih.gov

High expression of AKR1C1 is associated with proliferation and migration of small-cell lung cancer cells. [2022]