Combination Therapy for Solid Tumors

No longer recruiting at 4 trial locations

Overseen By Robert Atkinson, PhD, MSCR

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Adlai Nortye Biopharma Co., Ltd.

Must not be taking: NSAIDs, ACE inhibitors, ARBs, others

Disqualifiers: Active infection, CNS metastases, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments to determine their safety and effectiveness for patients with advanced solid tumors that cannot be surgically removed or have metastasized. It tests two experimental drugs, AN2025 and AN0025, alongside a known cancer drug, Atezolizumab (Tecentriq). The trial includes different groups to evaluate these combinations in varying doses, aiming to find the best balance of effectiveness and tolerability. Individuals previously treated for advanced cancer, who still have measurable disease and lack other treatment options likely to extend their life, might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new combination therapy.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking certain drugs like NSAIDs, ACE inhibitors, ARBs, or drugs that affect the CYP3A4 enzyme, you may need to switch to different medications before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that treatments like AN2025 and AN0025, when combined with Atezolizumab, remain in the early testing stages. Researchers closely monitor these combinations to assess their safety for people. So far, no major safety issues have emerged, but researchers continue to watch for any side effects.

Atezolizumab, one of the drugs in this trial, already treats some other cancers, indicating its general safety when used alone. However, when combined with new drugs like AN2025 and AN0025, researchers continue to gather detailed safety information. As this research is in the early stages, scientists work to find the best doses and remain vigilant for any serious side effects.

In summary, while no major safety problems have been identified yet, the safety of these drug combinations continues to be studied. This process is essential to ensure treatments are safe before becoming widely available. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination therapy of AN0025, AN2025, and Atezolizumab for solid tumors because it targets the condition in a unique way. Unlike traditional treatments that often focus on a single pathway, this combination leverages multiple mechanisms to potentially enhance the immune system's ability to fight cancer. AN2025 and AN0025 are investigational agents that may work synergistically with Atezolizumab, an immune checkpoint inhibitor, to boost its effectiveness. This multi-pronged approach aims to improve outcomes for patients who might not respond well to standard therapies like chemotherapy or radiation. By combining these drugs, researchers hope to reduce tumor progression more effectively than existing options.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research shows that Atezolizumab, when combined with chemotherapy, can reduce the risk of cancer recurrence or death by 50% compared to chemotherapy alone. Another study found that the average survival time for individuals taking Atezolizumab combinations was 16.5 months. In this trial, participants will receive different treatment combinations. One group will receive AN2025 and Atezolizumab, another will receive AN0025 and Atezolizumab, and a third will receive all three: AN0025, AN2025, and Atezolizumab. AN0025 and AN2025 are newer treatments being tested for their potential to improve these outcomes. These drugs aim to block specific pathways in cancer cells to prevent growth and spread. Early signs are promising, but more information is needed to fully understand their effectiveness. ^{1 6 7 8 9}

Who Is on the Research Team?

Robert Atkinson, PhD, MSCR

Principal Investigator

Adlai Nortye US Inc

Are You a Good Fit for This Trial?

Adults (18+) with advanced solid tumors who have signed consent, can follow the trial protocol, and have a life expectancy of at least 3 months. They must have measurable disease, adequate heart function, and acceptable organ function levels. Women must not be pregnant or breastfeeding and agree to contraception; men also need to use contraception. Participants should have had prior systemic therapy unless no other survival-prolonging options exist but no more than four lines of treatment for advanced disease.

Inclusion Criteria

Life expectancy ≥3 months

My organs are functioning well.

Left ventricular ejection fraction (LVEF) greater than 50% on echocardiography or multiple gated acquisition (MUGA) scan

Exclusion Criteria

Are currently participating in a study of an investigational agent or have used an investigational device within 4 weeks prior to the first dose of study treatment

I have severe nerve pain, lung or colon inflammation, high blood sugar, or uncontrolled thyroid issues from past treatments.

I have not had an infection needing treatment in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

DLT Observation Period I

Patients are treated with AN2025 and Atezolizumab until disease progression, unacceptable toxicity, or withdrawal of consent

3 weeks

1 visit every 3 weeks

DLT Observation Period II

Patients are treated with AN0025 and Atezolizumab until disease progression, unacceptable toxicity, or withdrawal of consent

3 weeks

1 visit every 3 weeks

DLT Observation Period III

Patients are treated with AN2025, AN0025, and Atezolizumab until disease progression, unacceptable toxicity, or withdrawal of consent

3 weeks

1 visit every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• AN0025
• AN2025
• Atezolizumab

Trial Overview The study is testing AN2025 and AN0025 in combination with Atezolizumab against advanced/metastatic tumors. It's an early-phase trial assessing safety, how well the body handles these drugs (pharmacokinetics), tolerability, and initial effectiveness. Patients will receive either double or triple combinations of these treatments.

How Is the Trial Designed?

Group I: DLT Observation Period III - AN2025, AN0025 and Atezolizumab Experimental Treatment 3 Interventions

The DLT Observation III will be started after safety data review by the investigators and the sponsor of the double combination treatments in Observations I and II. Patients enrolled in Observation III will start with the recommended dose of AN0025 from Observation II, 1200 mg Atezolizumab, and AN2025 will start from 50 mg QD. Patients will be treated with all three study drugs until the patient experiences disease progression, unacceptable toxicity or withdraws consent. The dose of Atezolizumab will be the same (i.e., 1200 mg Q3W) regardless of dose levels of AN2025 and cohorts. Atezolizumab is administered intravenously over 60 minutes every three weeks. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes. The dose of AN0025 as determined in Observation II will remain constant for each dose level of AN2025 and each cohort, unless the investigators and the sponsor determine that the toxicity comes from the AN0025 + Atezolizumab combination.

Group II: DLT Observation Period II - AN0025 and Atezolizumab Experimental Treatment 2 Interventions

During the DLT Observation II, patients will be treated with AN0025 and Atezolizumab until the patient experiences disease progression, unacceptable toxicity or withdraws consent. The starting dose of AN0025 is 250 mg. If tolerated, then a subsequent cohort will escalate to 500 mg. If 250 mg AN0025 is not tolerated, de-escalate to 125 mg. The dose of Atezolizumab will remain constant at 1200 mg Q3W for each dose level of AN0025 and in each cohort. Atezolizumab is administered intravenously over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.

Group III: DLT Observation Period I - AN2025 and Atezolizumab Experimental Treatment 2 Interventions

During the DLT Observation I, patients will be treated with AN2025 and Atezolizumab until the patient experiences disease progression, unacceptable toxicity or withdraws consent. The starting dose of AN2025 is 50 mg. If tolerated, then a subsequent cohort will escalate to 100 mg. A dose de-escalation cohort to 80 mg may occur if the 100 mg is not well tolerated. The dose of Atezolizumab will remain constant at 1200 mg every 3 weeks (Q3W) for each dose level of AN2025 and in each cohort. Atezolizumab is administered intravenously over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.

Who Is Running the Clinical Trial?

Adlai Nortye Biopharma Co., Ltd.

Lead Sponsor

Trials

8

Recruited

740+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04975958

NCT04975958 | Double/Triple Combinations of AN2025, ... This is an open-label, multicenter, Phase 1a study to evaluate the safety, tolerability, PK and preliminary efficacy of AN2025 and AN0025 in double or triple ...

2. data.intrinio.com data.intrinio.com/security/ANL:UW

Adlai Nortye Ltd. (ANL) Data ... AN0025, and Tecentriq or atezolizumab targeting a variety of PIK3CA mutant solid tumors. The atezolizumab used in this clinical trial is supplied by F.

3. asco.org asco.org/practice-patients/patient-resources/breaking-cancer-news-patients/asco-annual-meeting/atomic

Atezolizumab plus chemotherapy leads to 50% lower risk ... Treatment with atezolizumab and mFOLFOX6 chemotherapy leads to a 50% lower risk of cancer recurrence and death compared to patients treated with mFOLFOX6 alone.

4. oncologynewscentral.com oncologynewscentral.com/colorectal-cancer/immunotherapy-combo-first-to-show-overall-survival-benefit-in-certain-colorectal-cancers

Combo First to Show Overall Survival Benefit in Certain ... “The combination significantly prolonged overall survival compared to regorafenib in patients with previously treated metastatic colorectal ...

5. targetedonc.com targetedonc.com/view/atezolizumab-chemo-reduces-risk-of-recurrence-or-death-by-50-in-dmmr-colon-cancer

Atezolizumab/Chemo Reduces Risk of Recurrence or ... The combination of atezolizumab (Tecentriq) and standard chemotherapy reduced the risk of recurrence or death by 50% vs chemotherapy alone ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11891644/

Safety and Antitumor Activity of a Novel aCD25 Treg Depleter ... Two open-label, multicenter phase Ia/b studies were initiated to evaluate the safety, pharmacokinetic (PK) and pharmacodynamic (PD) properties, ...

7. adlainortye.com adlainortye.com/index.php/newsInfo?id=90

Media This is an open-label, multicenter, Phase Ia study to evaluate the safety, tolerability, PK and preliminary efficacy of AN2025 and AN0025 in ...

8. aacrjournals.org aacrjournals.org/cancerrescommun/article/doi/10.1158/2767-9764.CRC-24-0638/752047

Safety and anti-tumor activity of a novel aCD25 Treg depleter ... Safety and anti-tumor activity of a novel aCD25 Treg depleter RG6292 as a single agent and in combination with atezolizumab in patients with solid tumors.

9. prnewswire.com prnewswire.com/news-releases/adlai-nortye-announces-first-patient-dosed-in-phase-ia-clinical-trial-of-an2025-and-an0025-in-combination-with-atezolizumab-for-advanced-solid-tumors-301370899.html

Adlai Nortye Announces First Patient Dosed in Phase Ia ... This is an open-label, multicenter, Phase Ia study to evaluate the safety, tolerability, PK and preliminary efficacy of AN2025 and AN0025 in ...