A Study to Evaluate ANS014004 in Combination With EGFR-TKI in Non-Small Cell Lung Cancer

NCT07285148 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: ANS014004/PLB1004NSCLC-IbII-01
• Study Type: interventional
• Target: 253
• Locations: 1 country
• Sites: 1

Brief Summary

Protocol Title A Study to Evaluate ANS014004 in Combination with EGFR-TKI in Patients with EGFR Mutation-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer The main purpose of this research study is to Find a safe and tolerable dose of two investigational drugs, ANS014004 and PLB1004, when used together. Learn how effective this drug combination is at treating a type of lung cancer called "EGFR mutation-positive non-small cell lung cancer (NSCLC)" that has spread to other parts of the body (locally advanced or metastatic). This study is trying to answer the following questions: Safety \& Dosing: What are the side effects of combining ANS014004 and PLB1004? What is the best dose to use that patients can tolerate well? Effectiveness: Can this combination of drugs help shrink patients' tumors or stop them from growing? Background Information For patients with advanced lung cancer that has a specific gene change called an "EGFR mutation," targeted therapies known as EGFR-TKIs are a standard treatment. While these treatments often work well at first, most tumors eventually stop responding to the drug (this is called "acquired resistance"). The investigational drug ANS014004 is designed to block a protein called MET, which is one of the ways that tumors become resistant to EGFR-TKIs. The researchers believe that by combining ANS014004 with the EGFR-TKI PLB1004, they may be able to prevent or delay resistance, offering patients a more effective and longer-lasting treatment option. How will the study be conducted? This study is divided into two parts: Part 1 (Dose Escalation and Optimization): A small number of participants will receive different dose levels of ANS014004 combined with a fixed dose of PLB1004. The goal is to find the safest and most tolerable dose combination. Part 2 (Phase II Study): Once a recommended dose is identified, more participants will be enrolled to further evaluate how well the drug combination works against the cancer. Throughout the study, participants' health will be closely monitored, and their tumors will be measured regularly using imaging scans (like CT scans) to see how they respond to the treatment.

Conditions

Non-Small Cell Lung Cancer; EGFR Mutation; Metastatic Lung Cancer; MET Alteration

Outcome Measures

Primary Outcomes (4)

• Number of participants with dose-limiting toxicity (DLT) during the DLT observation period (Phase Ib Dose Escalation)

  To evaluate the tolerability of ANS014004 in combination with PLB1004. DLT is defined per NCI-CTCAE v5.0 (e.g., Grade 4 neutropenia lasting ≥7 days, febrile neutropenia, Grade 4 thrombocytopenia, Hy's Law-meeting hepatotoxicity, Grade ≥3 non-hematologic/non-hepatic toxicity excluding specified exceptions, etc.). The DLT observation period is the first 28 days after treatment initiation (including single-dose period and Cycle 1 of multiple-dose period). The outcome will be reported as the count and proportion of participants experiencing DLT in each dose group.

  2 years.

• Maximum tolerated dose (MTD) of ANS014004 in combination with PLB1004 (Phase Ib Dose Escalation)

  To determine the MTD of the combination therapy. MTD is defined as the highest dose level where ≤1 of 3-6 evaluable participants experience DLT during the DLT observation period. The outcome will be reported as the specific dose of ANS014004 (e.g., 45 mg QD, 60 mg QD) combined with fixed 80 mg QD PLB1004 that meets the MTD definition.

  2 years

• Objective Response Rate (ORR) assessed by investigator per RECIST v1.1 (Phase Ib Dose Optimization, Phase II)

  To evaluate the anti-tumor activity of ANS014004 in combination with PLB1004 (Phase Ib Dose Optimization) or ANS014004 combined with PLB1004/Osimertinib (Phase II) in EGFR mutation-positive locally advanced or metastatic NSCLC. ORR is defined as the proportion of participants with confirmed Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Tumor assessments are performed every 6 weeks (±7 days) for the first year and every 12 weeks (±7 days) thereafter. The outcome will be reported as the proportion of participants achieving ORR, with 95% confidence intervals (CIs) calculated using the Clopper-Pearson method.

  2 years

• Recommended Phase 2 Dose (RP2D) of ANS014004 in combination with PLB1004 (Phase Ib Dose Optimization)

  To identify the RP2D of the combination therapy. RP2D is determined based on comprehensive analysis of safety (incidence of AEs/DLTs), pharmacokinetic (PK) data, and preliminary efficacy (ORR, DCR) from the Phase Ib Dose Optimization period. The outcome will be reported as the specific dose of ANS014004 (e.g., 60 mg QD) combined with fixed 80 mg QD PLB1004 selected for Phase II.

  2 years.

Secondary Outcomes (11)

• Incidence and severity of adverse events (AEs) assessed by NCI-CTCAE v5.0 (All Phases)

  2 years

• Plasma maximum observed concentration (Cmax) of ANS014004 (All Phases)

  2 years

• Plasma area under the concentration-time curve from time 0 to last quantifiable time point (AUC0-t) of ANS014004 (All Phases)

  2 years

• Disease Control Rate (DCR) assessed by investigator per RECIST v1.1 (Phase Ib Dose Optimization, Phase II)

  2 years

• Duration of Response (DoR) assessed by investigator per RECIST v1.1 (Phase Ib Dose Optimization, Phase II)

  2 years

Study Arms (2)

ANS014004+PLB1004

EXPERIMENTAL

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).

Drug: ANS014004 + PLB1004

ANS014004 + Osimertinib

ACTIVE COMPARATOR

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

Drug: ANS014004 + Osimertinib

Interventions

ANS014004 + PLB1004 DRUG

1. Drug: ANS014004 Investigational Type II MET tyrosine kinase inhibitor (oral tablets). Dosing: Phase Ib escalation (30 mg, 45 mg, 60 mg, 75 mg QD); optimization uses selected doses; Phase II uses RP2D. Administered QD (≥1h before/2h after meals) in 21-day cycles. Targets MET exon 14 skipping, amplification, overexpression, and fusions. 2. Drug: PLB1004 Investigational irreversible EGFR tyrosine kinase inhibitor (oral capsules). Fixed dose: 80 mg QD. Administered QD (≥1h before/2h after meals) in 21-day cycles. Targets EGFR classical mutations (Ex19del, L858R), rare mutations, Ex20ins, and T790M.

ANS014004+PLB1004

ANS014004 + Osimertinib DRUG

1. Drug: ANS014004 (Same description as above, as the drug is identical across arms). 2. Drug: Osimertinib Market-approved third-generation EGFR tyrosine kinase inhibitor (oral tablets). Dosing: Per reference label (QD, with/without meals). Administered in 21-day cycles. Targets EGFR classical mutations (Ex19del, L858R) and T790M. Used as an active comparator.

ANS014004 + Osimertinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Male or female participants ≥18years of age at the time of signing the informed consent form.
• Patients with histologically or cytologically confirmed diagnosis of unresectable locally advanced (Stage IIIB and IIIC) or metastatic (Stage IV) NSCLC (according to the lung cancer staging criteria, refer to the eighth edition of the American Joint Committee on Cancer \[AJCC\] Lung Cancer Staging).
• Have a documented EGFR positive mutation (EGFR classic mutations including ex19del and ex21 L858R, uncommon mutations and ex20 insertion mutations) in tumor tissue samples or pleural fluid or blood samples.
• For Phase Ib dose escalation: have disease progression after the existing standard of care or intolerance to the existing standard of care or inappropriate or no effective standard of care is available (standard of care is defined as treatment recommended by the National Comprehensive Cancer Network \[NCCN\] guidelines \[including but not limited to chemotherapy, radiotherapy, targeted therapy based on mutation status, immunotherapy, and surgery\]). For participants who are considered intolerant to or ineligible for available standard therapy, or for whom effective standard therapy does not exist, the documentation of these reasons is required.
• For Phase Ib dose optimization and Phase II study: have or haven't received prior standard systemic therapy for advanced disease.
• Standard systemic therapy is referred to as (country-specific approved treatment will also be applied):
• EGFR classic mutations: EGFR-TKIs alone or in combination (examples, gefitinib and osimertinib with or without chemotherapy) for ex19del and ex21 L858R. Osimertinib or other third-generation EGFR TKI for T790M mutation.
• EGFR uncommon mutations: EGFR-TKIs or chemotherapy for uncommon mutations including but not limited to G719X, S768I, L861Q mutations.
• EGFR exon 20 activating insertions: chemotherapy with or without amivantamab or country-specific approved EGFR TKIs.
• For China only: the presence of MET amplification and/or overexpression in tumor tissue samples or pleural fluid or blood samples collected after progression on prior EGFR-TKI treatment, confirmed by a central /local laboratory.
• MET amplification is defined as the presence of MET amplification confirmed by nextgeneration sequencing (NGS) technology or mean MET gene copy number (GCN) ≥ 4 per cell or the ratio of MET to chromosome enumerating probe against chromosome 7 (MET/CEP7) ≥2.0 confirmed by fluorescence in situ hybridization (FISH) testing.
• MET overexpression is defined as immunohistochemistry (IHC) ≥ 2+ (local or central lab test results are accepted).
• Have at least one measurable target lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• ECOG PS ≤ 1.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Have other known primary driver gene alterations. For example, NSCLC with a targetable alteration in ALK, RET, ROS1, BRAF, KRAS, etc. The investigators should discuss enrollment with the sponsor regarding co-mutations.
• Prior treated with hepatocyte growth factor (HGF) targeted therapy or other MET-TKIs (including Type I and Type II), e.g., gulmonertinib, savolitinib, capmatinib, tepotinib, bozitinib, cabozantinib, glenitinib and almonertinib.
• Participation in other therapeutic clinical trials within 28 days prior to the first dose of study treatment.
• Received anti-tumor therapy (chemotherapy, immunotherapy, hormone therapy, targeted therapy, biological therapy or other anti-tumor therapy, except for hormones for hypothyroidism or estrogen replacement therapy, anti-estrogen analogs, and agonists required to inhibit serum testosterone levels) within 14 days or 5 half-lives (whichever is shorter) of the first dose of study treatment. The following exceptions are:
• Nitrosourea or mitomycin-C within 6 weeks prior to the first dose of study treatment.
• Chinese medicines with anti-tumor indications within 7 days prior to the first dose of study treatment.
• Radiotherapy with a wide field of radiation within 28 days, or radiotherapy with a limited field of radiation for palliation within 14 days of the first dose of study treatment.
• Participants must have recovered from all radiation related toxicity, not requiring corticosteroids.
• Major surgery, other than diagnostic surgery, within 4 weeks of the first study treatment or is expected during the study.
• Toxicities of prior therapy have not been resolved to Grade ≤1 or to baseline, as evaluated by NCI-CTCAE v5.0. NOTE: Participants with Grade 2 toxicities can be enrolled if the toxicities as stable and do not affect the safety of participating in this study (e.g., alopecia, skin hyperpigmentation, neuropathy).
• History of another primary malignancy that has been diagnosed or required therapy within the past 3 years (other than adequately treated local basal cell or squamous cell carcinoma of the skin; or any other cancer in situ currently in complete remission).
• Have central nervous system (CNS) metastases that are symptomatic or clinically unstable or require increased steroid dose to manage CNS symptoms within 4 weeks prior to the first dose of study treatment.
• Participants with symptomatic CNS metastases may participate in the study providing that symptoms are controlled after treatment, clinically stable for at least 4 weeks and have no evidence of new or enlarged brain metastases.
• Participants with carcinomatous meningitis or meningeal metastases, or spinal cord compression are excluded regardless of clinical stability.

Sponsors & Collaborators

• Avistone Biotechnology Co., Ltd.: collaborator
• Beijing Pearl Biotechnology Limited Liability Company: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center David H, Koch Center lor Cancer Care

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2025
• First Posted: December 16, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: December 16, 2025

Record last verified: 2025-12

Locations

US (1)