ANS014004 + EGFR-TKI for Non-Small Cell Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Beijing Pearl Biotechnology Limited Liability Company

Must be taking: EGFR-TKIs

Must not be taking: MET-TKIs

Disqualifiers: Other driver gene alterations, CNS metastases, others

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with EGFR mutation-positive non-small cell lung cancer that has metastasized. Researchers aim to determine a safe dose of two experimental drugs, ANS014004 and PLB1004, and assess their combined effectiveness in shrinking tumors or halting their growth. The trial seeks participants whose cancer has an EGFR mutation and has progressed after standard treatments. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new treatment.

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

Research shows that the drug PLB1004, when used alone, effectively combats cancer and is generally well-tolerated by patients. For those with a specific type of lung cancer, PLB1004 has long-lasting effects, maintaining its efficacy over time.

Studies on the combination of ANS014004 and Osimertinib have found Osimertinib to be safe, with no unexpected safety issues in similar treatments.

As this trial is in its early stages, the main goal is to determine a safe and tolerable dose for combining ANS014004 with either PLB1004 or Osimertinib. Detailed safety information is still being gathered. However, testing these treatments suggests some confidence in their potential safety for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ANS014004 and its combinations because these treatments offer a fresh approach for tackling non-small cell lung cancer (NSCLC) with EGFR mutations. Unlike current standard treatments like Osimertinib, which solely targets the EGFR pathway, ANS014004 in combination with PLB1004 or Osimertinib targets multiple pathways that could enhance treatment effectiveness. ANS014004 potentially works by overcoming resistance mechanisms often seen in standard EGFR-targeted therapies, which could lead to better outcomes for patients, particularly those with advanced stages of the disease. By targeting multiple pathways, these combinations could provide more comprehensive cancer control and reduce the likelihood of tumor resistance.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that treatments like PLB1004 and osimertinib are effective for non-small cell lung cancer (NSCLC) with specific EGFR gene changes. However, these treatments may lose effectiveness over time. ANS014004 is a new drug designed to block a protein called MET, which might cause this resistance. Early research suggests that using ANS014004 with either PLB1004 or osimertinib, as studied in this trial, could help prevent resistance. One study found that combining a similar MET blocker with osimertinib improved patient outcomes, indicating that these new combinations might also be effective. Both combinations in this trial aim to shrink tumors or slow their growth in people with advanced NSCLC. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for patients with advanced non-small cell lung cancer that has spread and have a specific gene change called an 'EGFR mutation.' They should not have had previous treatments that failed. The study seeks to determine the safety and effectiveness of combining two investigational drugs, ANS014004 and PLB1004 (or Osimertinib), in these individuals.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

Life expectancy of ≥12 weeks

I may or may not have had treatment for my advanced disease.

Exclusion Criteria

Side effects from my previous treatments have mostly gone away or returned to normal.

I have recently undergone radiotherapy.

Known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation and Optimization

Participants receive different dose levels of ANS014004 combined with a fixed dose of PLB1004 to find the safest and most tolerable dose combination.

28 days for DLT observation period

Regular visits for monitoring and dose adjustments

Phase II Study

Participants receive the recommended dose to evaluate the efficacy of the drug combination against cancer.

2 years

Tumor assessments every 6 weeks for the first year, every 12 weeks thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ANS014004
• PLB1004

Trial Overview

The trial tests ANS014004 combined with EGFR-TKI therapies (PLB1004 or Osimertinib) to find a safe dose and assess how well this combination can treat lung cancer by potentially preventing drug resistance. It's conducted in two parts: first finding the best dose, then expanding to more participants to evaluate effectiveness.

How Is the Trial Designed?

Group I: ANS014004+PLB1004 Experimental Treatment 1 Intervention

The Phase Ib study consists of two parts: dose escalation and dose optimization. The dose escalation part will enroll participants with EGFR mutation-positive locally advanced or metastatic NSCLC who have received prior standard therapy in order to evaluate the safety and tolerability of the combination therapy and determine the maximum tolerated dose (MTD) (if any); The dose optimization part will further expand the population to include participants with EGFR mutation-positive locally advanced or metastatic NSCLC who have not received prior systemic therapy for advanced disease or have received standard therapy to determine the recommended Phase 2 dose (RP2D).

Group II: ANS014004 + Osimertinib Active Control 1 Intervention

participants will be enrolled in into two cohorts according to the prior anti-tumor treatment received. * Cohort A: participants with EGFR mutation-positive (excluding exon 20 insertions) locally advanced or metastatic NSCLC who have not received prior standard systemic therapy for advanced disease. Participants who meet the inclusion criteria will be stratified according to baseline brain metastasis status (present vs. absent) and be randomized at a ratio of 2:1 to receive the combination treatment of ANS014004 and PLB1004 or the combination treatment of ANS014004 and Osimertinib. * Cohort B: participants with EGFR mutation-positive (excluding exon 20 insertions) locally advanced or metastatic NSCLC who previously received standard systemic therapy. Participants who meet the inclusion criteria will be stratified according to baseline MET amplification and/or overexpression status (present vs. absent) and be randomized at a ratio of 2:1 to receive the combination treatment of ANS0140

Who Is Running the Clinical Trial?

Beijing Pearl Biotechnology Limited Liability Company

Lead Sponsor

Trials

6

Recruited

480+

Avistone Biotechnology Co., Ltd.

Industry Sponsor

Trials

10

Recruited

1,400+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07285148

A Study to Evaluate ANS014004 in Combination With ...

Learn how effective this drug combination is at treating a type of lung cancer called "EGFR mutation-positive non-small cell lung cancer (NSCLC) ...

2.

clin.larvol.com

clin.larvol.com/trial-detail/NCT07285148

A Study to Evaluate ANS014004 in Combination With ...

The outcome will be reported as median OS with 95% CIs, using the Kaplan-Meier method. 2 years. Non-Small Cell Lung Cancer Symptom Assessment Questionnaire ( ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39462746/

Treatment Patterns and Clinical Outcomes in Patients With ...

The continuation of osimertinib with chemotherapy was associated with superior progression-free survival (PFS; median: 10.1 versus 5.9 months, Hazard Ratio [HR ...

4.

cancerbiomed.org

cancerbiomed.org/content/22/3/237

Expert consensus on the diagnosis and treatment of non ...

The INSIGHT 2 study, which was led by Wu, demonstrated that combining a highly selective MET inhibitor (tepotinib) with osimertinib is effective ...

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39576954/

A Systematic Review and Single-Arm Meta-Analysis

Osimertinib demonstrated robust response in NSCLC harboring uncommon EGFR mutations, without unanticipated safety concerns.

6.

trial.medpath.com

trial.medpath.com/clinical-trial/5c463889f0e57c59/nct07285148-ans014004-egfr-tki-non-small-cell-lung-cancer

A Study to Evaluate ANS014004 in Combination With EGFR ...

Learn how effective this drug combination is at treating a type of lung cancer called "EGFR mutation-positive non-small cell lung cancer (NSCLC) ...

7.

asco.org

asco.org/abstracts-presentations/ABSTRACT495544

Clinical outcomes of first-line osimertinib in NSCLC ...

This study aimed to retrospectively analyze the efficacy and safety profiles of first-line osimertinib in EGFR-mutated NSCLC and explore the factors that could ...