AN4005 for Advanced Cancer

Recruiting at 7 trial locations

Overseen By Kirsten Lee

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Adlai Nortye Biopharma Co., Ltd.

Must not be taking: Immunosuppressants, Steroids, Antibiotics, others

Disqualifiers: Autoimmune disease, Cardiovascular impairment, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 1 year

31 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AN4005 for individuals with advanced cancers, including certain challenging types of lymphoma. The main goal is to determine the safety of AN4005 and its behavior in the body, with various doses tested to find the safest and most effective amount. It is open to those with advanced solid tumors or lymphoma that have not responded to other treatments. This trial might suit those whose cancer has not improved with available therapies. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain drugs that affect liver enzymes (CYP3A4, UGT, P-gP) two weeks before and during the trial. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that AN4005 is likely to be safe for humans?

Research has shown that AN4005 is generally safe for patients with advanced tumors. In studies, patients tolerated AN4005 well, experiencing no severe side effects. The drug controlled tumor growth as effectively as other approved treatments, without causing major problems.

In early trials, AN4005 demonstrated safety and manageability for patients. Although these tests are ongoing, the evidence so far suggests the treatment is safe. This trial will continue to determine the optimal dose that remains safe for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

AN4005 is unique because it targets advanced cancer with a potentially novel approach. Unlike many existing treatments that focus on chemotherapy or immunotherapy, AN4005 is being investigated for its pharmacokinetics, particularly how a high-fat meal might affect its absorption and effectiveness. Researchers are excited about AN4005 because it has a dose-escalation strategy that aims to find the most effective and safe dose quickly, potentially allowing for more personalized cancer treatment. This flexibility in dosing could lead to better outcomes by minimizing side effects while maximizing efficacy.

What evidence suggests that AN4005 might be an effective treatment for advanced cancer?

Research has shown that AN4005, a pill that blocks a protein called PD-L1, is safe and well-tolerated in people with advanced cancer. Early studies suggest it might help the immune system fight cancer by inhibiting a protein that tumors use to hide. This trial will evaluate AN4005 across various treatment arms, including different dose levels and the effect of a high-fat meal on its pharmacokinetics. Although still in the early testing phase, initial evidence suggests it could be effective for certain types of tumors. AN4005 might help slow down or shrink tumors in some patients. However, more research is needed to confirm these findings and understand its effectiveness in different situations. ^{1 2 6 7 8}

Who Is on the Research Team?

Kevin Dryer

Principal Investigator

Adlai Nortye USA Inc

Are You a Good Fit for This Trial?

Adults with advanced solid tumors or relapsed/refractory lymphoma, who have no standard treatment options left. They must be expected to live at least 3 months, have a performance status of 0 or 1 (able to carry out daily activities), and meet certain organ function criteria. Pregnant or breastfeeding women are excluded, as well as those with recent infections, vaccinations, other treatments, or severe allergies.

Inclusion Criteria

Provided archival tumor tissue sample or newly obtained biopsy

I have provided a recent biopsy of my tumor, not previously treated with radiation.

Standard treatments are not suitable or tolerable for me.

Exclusion Criteria

Currently participating in another investigational study within 4 weeks or less than 5 half-lives

I have not had another cancer in the last 2 years, with some exceptions.

I have not taken any antibiotics by mouth or IV in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive increasing doses of AN4005 to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)

Up to 28 days per dose level

Multiple visits for dose escalation and safety monitoring

Treatment

Participants receive AN4005 at the determined MTD/RP2D

Up to 1 year

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 90 days

What Are the Treatments Tested in This Trial?

Interventions

• AN4005

Trial Overview AN4005 is being tested in various doses on patients with advanced tumors to assess its safety and tolerability. This first-in-human study uses a '3 + 3 design' for dose escalation to find the maximum tolerated dose (MTD) and/or recommended phase two dose (RP2D).

How Is the Trial Designed?

Group I: AN4005 food effect Active Control 1 Intervention

The effect of a high-fat meal on the PK of AN4005 will be evaluated in a separate cohort of approximately 6 patients after a safe and clinically relevant dose is identified during the dose finding part of the study.

Group II: AN4005 dose level 0 Active Control 1 Intervention

One sentinel patient will be orally dosed at 50 mg AN4005 BID. If this dose for one cycle is deemed to be tolerable upon review of safety data and PK data, the dose of AN4005 will be escalated to next level: dose level 1.

Group III: AN4005 dose level 1 Active Control 1 Intervention

Three patients will be orally dosed at 100 mg AN4005 BID. Based on the number of DLT events during the first cycle, dosing decisions will be made, including add 3 patients at the same dose level (1 DLT), escalation to dose level 3 (\<1/6 DLT), de-escalate to lower dose or stop (\>1/6 DLT).

Group IV: AN4005 dose level 2 Active Control 1 Intervention

Three patients will be orally dosed at 200 mg AN4005 BID. Based on the number of DLT events during the first cycle, dosing decisions will be made, including add 3 patients at the same dose level (1 DLT), escalation to dose level 3 (\<1/6 DLT), de-escalate to lower dose or stop (\>1/6 DLT).

Group V: AN4005 dose level 3 Active Control 1 Intervention

Three patients will be orally dosed at 400 mg AN4005 BID. Based on the number of DLT events during the first cycle, dosing decisions will be made, including add 3 patients at the same dose level (1 DLT), escalation to dose level 4 (\<1/6 DLT), de-escalate to lower dose or stop (\>1/6 DLT).

Group VI: AN4005 dose level 4 Active Control 1 Intervention

Three patients will be orally dosed at 600 mg AN4005 BID. Based on the number of DLT events during the first cycle, dosing decisions will be made, including add 3 patients at the same dose level (1 DLT), de-escalate to lower dose or stop (\>1/6 DLT).

Who Is Running the Clinical Trial?

Adlai Nortye Biopharma Co., Ltd.

Lead Sponsor

Trials

8

Recruited

740+

Citations

1. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A792

691 A phase I study of AN4005, an orally available PD-L1 ... Conclusions AN4005 demonstrated favorable safety and tolerability in patients with advanced tumors. The preliminary efficacy of AN4005 in a ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04999384

First in Human, Dose Escalation Study of AN4005 Open-label, multicenter, phase 1 study to investigate the safety, tolerability, and PK of AN4005 in patients with advanced tumors.

3. ir.adlainortye.com ir.adlainortye.com/static-files/d8f0861e-bc11-46b2-af40-df7f53b5e607

A Phase I study of AN4005, an orally available PD-L1 inhibitor ... AN4005 demonstrated favorable safety and tolerability in patients with advanced tumors. • The preliminary efficacy of AN4005 in a tumor type ...

4. jitc.bmj.com jitc.bmj.com/content/jitc/12/Suppl_2/A792.full.pdf

Abstracts - A PHASE I STUDY OF AN4005, AN ORALLY ... Conclusions AN4005 demonstrated favorable safety and toler- ability in patients with advanced tumors. The preliminary effi- cacy of AN4005 in a tumor type known ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT04999384

First in Human, Dose Escalation Study of AN4005 A phase I study of AN4005, an orally available PD-L1 inhibitor, in patients with advanced tumors: safety and preliminary efficacy

6. adlainortye.com adlainortye.com/index.php/product_info?id=4

AN4005 - Pipeline In preclinical studies, AN4005 was well tolerated and exhibited tumor growth inhibition (TGI) comparable to FDA-approved anti-PD-L1 antibody. In addition, the ...

7. withpower.com withpower.com/trial/phase-1-7-2021-e6971

AN4005 for Advanced Cancer This trial tests a new drug, AN4005, in patients with advanced tumors. It aims to find the highest safe dose by adjusting the amount given over time. Show more.

8. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT04999384?keyword=%22Advanced%22

First in Human, Dose Escalation Study of AN4005 If 50 mg BID for one cycle is deemed to be tolerable upon review of safety data, the dose of AN4005 will be escalated to 100 mg BID in a cohort of 3 patients, ...