ARV-393 for Non-Hodgkin's Lymphoma

Recruiting at 16 trial locations

Overseen By Arvinas Corporation, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Arvinas Inc.

Disqualifiers: Transplant, Infection, Lung disease, others

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

Compensation: Varies

Number of Visits: Unknown

112 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ARV-393, to determine its safety and effectiveness in treating non-Hodgkin's lymphoma, a cancer affecting the lymphatic system. ARV-393 may work by breaking down a protein in cancer cells, potentially stopping tumor growth. The trial will begin by testing various doses to identify the safest and most effective amount. Individuals who have tried at least two previous treatments for their lymphoma without success and have a measurable tumor may be suitable candidates for this trial. As a Phase 1 trial, this research aims to understand how ARV-393 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that you cannot have had certain treatments like radiotherapy or systemic anticancer treatment shortly before starting the trial. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that ARV-393 is likely to be safe for humans?

Research shows that ARV-393 is a new treatment being tested for non-Hodgkin's lymphoma, a type of blood cancer. This trial marks the first use of ARV-393 in humans, so no safety data from human use exists yet. The main goal of this early-stage trial is to assess the safety of ARV-393 for humans. Researchers will closely monitor how participants handle the treatment and any side effects they might experience.

As this is an early-stage trial, no previous safety data from human use is available. However, the trial will carefully monitor participants for any signs of negative effects to ensure safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for non-Hodgkin's lymphoma, like chemotherapy and monoclonal antibodies, work by broadly attacking cancer cells or marking them for the immune system to destroy. But ARV-393 is different. It utilizes a novel mechanism called targeted protein degradation, which means it can specifically target and degrade proteins essential for cancer cell survival. This approach may lead to more effective cancer cell elimination with potentially fewer side effects, which is why researchers are excited about its potential.

What evidence suggests that ARV-393 might be an effective treatment for non-Hodgkin's lymphoma?

Research has shown that ARV-393 could help treat non-Hodgkin's lymphoma. In lab studies, ARV-393 successfully broke down a protein essential for the growth of many of these cancers. This resulted in a significant reduction in tumor size across various tests. In some cases, it halted up to 99% of tumor growth. These early findings suggest that ARV-393 might slow or stop tumor growth in people with this type of cancer. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with advanced non-Hodgkin's lymphoma that has come back or hasn't responded to treatment. Participants should have specific types of this cancer, like AITL, B-Cell Lymphoma, or T-Cell Lymphoma. Details on who can join are not fully listed here.

Inclusion Criteria

Participants must also have ≥1 measurable lesion at study entry

My B-cell non-Hodgkin lymphoma has not responded to 2 or more treatments, or my AITL has worsened after standard treatment.

My organs are functioning well.

Exclusion Criteria

Participants with an inability to comply with listed prohibited treatments

I haven't had certain cancer treatments recently before starting ARV-393.

I do not have any severe illnesses or infections that would make joining this study unsafe for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ARV-393 in a dose escalation format to evaluate safety and tolerability

4 months

Regular visits for dose adjustments and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

At least 30 days

Long-term Follow-up

Participants are assessed for overall response rate and duration of response

Approximately 2 years

What Are the Treatments Tested in This Trial?

Interventions

• ARV-393

Trial Overview The study is testing ARV-393, a new drug given as an oral tablet. It aims to see if it's safe and effective against certain non-Hodgkin's lymphomas by targeting a protein linked to tumor growth.

How Is the Trial Designed?

Group I: Dose escalation Experimental Treatment 1 Intervention

Dose escalation will begin at Dose Level 1. Dose escalation or de-escalation decision will be recommended by the cohort review committee.

Who Is Running the Clinical Trial?

Arvinas Inc.

Lead Sponsor

Trials

4

Recruited

730+

Published Research Related to This Trial

A pharmacovigilance analysis of 362 reports revealed that ALK-TKIs, particularly crizotinib and alectinib, are associated with cardiac arrhythmias, affecting more men than women with a median age of 68.

The onset of cardiac arrhythmias varies significantly among different ALK-TKIs, indicating that the timing of these adverse effects cannot be easily predicted after starting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac arrhythmias associated with anaplastic lymphoma kinase (ALK) inhibitors: an analysis of the FDA Adverse Event Reporting System (FAERS). Wang, F., Xu, G., Wu, X.[2023]

Antiretroviral (ARV) medications have been safely used for 20 years in HIV treatment, with an evolving understanding of their potential short-term and long-term side effects.

The safety profile of ARVs is improving with newer combinations and medications, but ongoing monitoring for side effects remains essential, especially in resource-limited settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of antiretroviral drugs. Tymchuk, CN., Currier, JS.[2019]

A total of 921 adverse drug reactions (ADRs) were reported to NAFDAC from January to June 2015, with a higher incidence in females (65.5%) and the age group of 21-40 years (45.6%).

The most common suspected drug associated with ADRs was the Zidovudine/Lamivudine/Nevirapine combination, particularly in patients with HIV, highlighting the need for careful monitoring of patients on antiretroviral therapy due to their increased risk of ADRs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of adverse drug reaction signals in NAFDAC pharmacovigilance activities from January to June 2015: safety of drug use in Nigeria. Awodele, O., Aliu, R., Ali, I., et al.[2021]

Adverse drug reactions (ADRs) are common in pediatric patients with oncohematological diseases, with incidence rates ranging from 14.4% to 67% in inpatients and 19.6% to 68.1% during admissions, highlighting the need for careful monitoring in this vulnerable population.

The severity of ADRs can be significant, with 11% to 16.4% classified as severe, yet most studies lacked a thorough assessment of preventability, indicating a gap in safety protocols that could be improved for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Drug Reactions in Pediatric Oncohematology: A Systematic Review. Amaro-Hosey, K., Danés, I., Agustí, A.[2022]

Between 1999 and 2003, a study at Toulouse University Hospital reported 613 adverse drug reactions (ADRs) from antiretroviral drugs affecting 428 patients, highlighting the importance of monitoring these effects.

Most reported ADRs (88.6%) were classified as 'non-serious', but 57% of cases required stopping the suspected medication, indicating that while many reactions were mild, a significant portion still necessitated intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Not Available]. Bandrant, M., Bagheri, H., Cuzin, L., et al.[2016]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06393738?term=NCT06393738

A Study of ARV-393 in Relapsed/Refractory Non-Hodgkin ... ARV-393 is thought to work by breaking down a protein present in many types of non-Hodgkins lymphomas, which may prevent, slow or stop tumor growth. This is ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124093327

Phase 1 Study of ARV-393, a PROTAC BCL6 Degrader ... Additionally, ARV-393 demonstrated dose-responsive tumor growth inhibition that correlated with BCL6 degradation in several cell line-derived ...

3. ir.arvinas.com ir.arvinas.com/news-releases/news-release-details/arvinas-presents-preclinical-data-protac-bcl6-degrader-arv-393

Arvinas Presents Preclinical Data for PROTAC BCL6 ... Single-agent ARV-393 significantly reduced tumor burden in peripheral blood, bone marrow and spleen in a systemic PDX model of nTFHL-AI derived ...

4. nasdaq.com nasdaq.com/articles/arvinas-inc-reports-positive-preclinical-results-arv-393-models-non-hodgkin-lymphoma-eha

Arvinas, Inc. Reports Positive Preclinical Results for ARV ... ARV-393 effectively reduced tumor burden across various models and suggested potential broad utility across different non-Hodgkin lymphoma ...

5. library.ehaweb.org library.ehaweb.org/eha/2025/eha2025-congress/4159412/anna.van.acker.arv-393.a.protac.bcl6.degrader.is.efficacious.in.preclinical.html?f=

ARV-393, A PROTAC BCL6 DEGRADER, IS ... In the two tFL PDX models, ARV-393 resulted in 99% and 95% tumor growth inhibition (TGI). Lastly, ARV-393 demonstrated complete tumor regressions with ...

6. medchemexpress.com medchemexpress.com/arv-393.html?srsltid=AfmBOopPGrv0Q0CoA5GzkLVV6SSReAwjPgwHTd8Y06gy71rpyZ97nkS0

ARV-393 | BLC6 PROTAC Degrader ARV-393 has the potential for the research of advanced non-hodgkin lymphoma. ... SAFETY DATA SHEET (SDS). English - EN (252 KB) Français - FR (252 KB) ...

7. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/ND05/742760/Abstract-ND05-The-discovery-of-ARV-393-a-potent

Abstract ND05: The discovery of ARV-393, a potent, orally ... This effort identified ARV-393, an orally bioavailable PROTAC® that recruits BCL6 and the E3 ligase cereblon to rapidly degrade BCL6 via the cell's natural ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025022955

Phase 1 Study of ARV-393, a PROTAC BCL6 Degrader, in ... To evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of ARV-393 in patients with advanced B-cell NHL or ...