What is the mechanism of action of this treatment?

The most common treatments for solid tumors include immunotherapies, targeted therapies, and chemotherapy. Immunotherapies, such as PD-L1 inhibitors like Atezolizumab, work by blocking the interaction between PD-L1 on tumor cells and PD-1 on T-cells, thereby enhancing the immune system's ability to attack cancer cells. Targeted therapies aim at specific genetic mutations or proteins that drive cancer growth, while chemotherapy uses cytotoxic drugs to kill rapidly dividing cells. For patients with solid tumors, these treatments are crucial as they offer different mechanisms to control or eliminate cancer, potentially improving survival rates and quality of life.

What side effects are associated with this type of intervention?

Common side effects of treatments for solid tumors, particularly those involving PD-L1 inhibitors like Atezolizumab, include fatigue, nausea, decreased appetite, and anemia. Serious adverse events can include grade 3 or higher toxicities such as dermatitis, pneumonitis, and hepatic dysfunction. Combination therapies with chemotherapy can further introduce side effects like neutropenia, peripheral neuropathy, and gastrointestinal disturbances. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

Atezolizumab, a PD-L1 inhibitor, has received FDA approval for various solid tumors, including non-small cell lung cancer (NSCLC) and triple-negative breast cancer (TNBC). In NSCLC, Atezolizumab has been approved in combination with chemotherapy agents like carboplatin and nab-paclitaxel. Similarly, Pembrolizumab, another PD-1 inhibitor, has been approved for NSCLC and other solid tumors, often in combination with chemotherapy. These approvals highlight the efficacy of immune checkpoint inhibitors in combination with other treatments for solid tumors.

What other types of research exist?

Promising alternatives to AN2025 and AN0025 in combination with Atezolizumab for solid tumors include: 1) Pembrolizumab (another PD-1 inhibitor) in combination with chemotherapy, which has shown efficacy in various solid tumors including NSCLC and colorectal cancer. 2) Nivolumab (a PD-1 inhibitor) combined with Ipilimumab (a CTLA-4 inhibitor), which has demonstrated activity in NSCLC and renal cell carcinoma. 3) Atezolizumab combined with Bevacizumab and chemotherapy, which has shown positive results in NSCLC and renal cell carcinoma. These combinations have been evaluated in multiple phase 2 and phase 3 trials, showing promising efficacy and safety profiles.

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Other

Combination Therapy for Solid Tumors

Phase 1

Waitlist Available

Research Sponsored by Adlai Nortye Biopharma Co., Ltd.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

Have received no more than 4 prior lines of systemic therapy for advanced disease. Prior therapy in an adjuvant or neoadjuvant setting is not considered as a prior line of systemic therapy

Must not have

Have been discontinued treatment due to a Grade 3 or higher immune-related AE (irAE) from prior anti-PD-1or anti-PD-L1, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137)

Patient that is currently receiving angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs): Patients on these hypertensives at study entry should be switched to other hypertensives prior to study drug dosing

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two new drugs, AN2025 and AN0025, alone and with an existing cancer drug, Atezolizumab, in patients with advanced or spreading tumors. The goal is to see if these new drugs can help fight cancer better, either by themselves or by enhancing the effects of Atezolizumab.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include reactions related to immune system activation such as inflammation in various organs which could lead to symptoms like fatigue, digestive issues or skin problems; allergic reactions specific to drug components; increased risk of infections due to lowered immunity; possible liver enzyme elevations.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or restricted in physically strenuous activity but can do light work.

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I have had 4 or fewer treatments for my advanced disease, not counting early-stage treatments.

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I am 18 or older and have signed the consent form for this trial.

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My cancer is advanced and cannot be removed by surgery.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I stopped treatment due to a severe side effect from prior immunotherapy.

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I am willing to switch my blood pressure medication before starting the study drug.

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I am on high-dose steroids or other drugs that weaken my immune system.

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I have received an organ or tissue transplant from another person.

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I have severe pain from my cancer that isn't controlled by medication.

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I have active tuberculosis.

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I am currently taking NSAIDs.

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I have not had major surgery in the last 4 weeks or have fully recovered if I did.

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I do not have serious heart problems like recent heart attacks or uncontrolled high blood pressure.

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I cannot take pills due to a stomach condition or have issues like severe nausea.

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I need frequent procedures to remove fluid buildup in my body at least once a month.

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My cancer has spread to the lining of my brain and spinal cord.

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I am allergic to some ingredients in atezolizumab or similar drugs.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Measure - Dose Limiting Toxicities (DLTs)

Measure - Number of participants with adverse events and serious adverse events

Secondary study objectives

Duration of Response (DOR)

Efficacy by Phosphatidylinositol-4,5-bisphosphate 3 Kinase Catalytic Subunit Alpha (PIK3CA) mutation in DLT Observations I and III

Overall Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: DLT Observation Period III - AN2025, AN0025 and AtezolizumabExperimental Treatment3 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 AtezolizumabExperimental Treatment2 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 AtezolizumabExperimental Treatment2 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.

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for solid tumors include immunotherapies, targeted therapies, and chemotherapy. Immunotherapies, such as PD-L1 inhibitors like Atezolizumab, work by blocking the interaction between PD-L1 on tumor cells and PD-1 on T-cells, thereby enhancing the immune system's ability to attack cancer cells. Targeted therapies aim at specific genetic mutations or proteins that drive cancer growth, while chemotherapy uses cytotoxic drugs to kill rapidly dividing cells. For patients with solid tumors, these treatments are crucial as they offer different mechanisms to control or eliminate cancer, potentially improving survival rates and quality of life.

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