Clinical Trials/NCT06328439

NCT06328439

Active, not recruiting

Phase 1

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ANS014004 Monotherapy in Subjects With Locally Advanced or Metastatic Solid Tumors

Avistone Biotechnology Co., Ltd.1 site in 1 country40 target enrollmentMay 19, 2024

ConditionsLocally Advanced or Metastatic Solid Tumors

InterventionsANS014004

DrugsANS014004

Overview

Phase: Phase 1
Intervention: ANS014004
Conditions: Locally Advanced or Metastatic Solid Tumors
Sponsor: Avistone Biotechnology Co., Ltd.
Enrollment: 40
Locations: 1
Primary Endpoint: Proportion of patients with radiological response (ORR)
Status: Active, not recruiting
Last Updated: last month

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief Summary

Brief Summary: This is a Phase I, first-in-human, open-label, multi-center study designed to explore the safety, tolerability, PK, and anti-tumor antitumor activity of ANS014004 monotherapy in subjects with locally advanced or metastatic solid tumors.

The study consists of two parts: a dose-escalation part (Part 1) and a dose-expansion part (Part 2). For each subject, the study will consist of a screening period (Day -28 to Day -1), a treatment period (until discontinuation of treatment) and a follow-up period (including safety follow-up and survival follow-up).
During the Treatment Period, subjects will receive ANS014004 single-agent oral administration until the subject meets any treatment termination criteria.
1. The dose escalation phase (Part 1) will consist of a single-dose period and a multiple-dose period (28 days as one cycle). Subjects in the dose escalation phase will receive a single dose of ANS014004 on Day 1 of the single-dose period to obtain the complete PK profile of a single dose. There will be a 7-day washout period between the single-dose period and the multiple-dose period at the same dose level. If no dose-limiting toxicity (DLT) occurs within the 7-day washout period, subjects will start multiple-dose treatment on Day 8 (28 days per cycle), receiving ANS014004 once daily (QD) or twice daily (BID). Dose escalation will first be conducted in the QD dosing cohort. When the dose escalates to Cohort 5, dose escalation in the BID dosing cohort with the same daily dose will be conducted in parallel. For each group with the same daily dose of QD or BID cohorts, subjects will be enrolled in the QD cohort first, followed by the BID cohort, and then dose escalation of the next daily dose of QD or BID cohorts will be conducted. Both the QD and BID dosing cohorts will include a single-dose period and a multiple-dose period. Based on the safety, PK and preliminary efficacy data of the QD and BID cohorts, the dosing frequency and dose of the backfill cohort will be selected. Subjects in the backfill cohort will directly enter the multiple-dose period. The RP2D will be determined based on the comprehensive assessment of safety, PK and preliminary efficacy data from the dose escalation phase.
2. In the dose expansion portion (Part 2), subjects will receive oral administration of ANS014004 at the RP2D dose QD or BID in each treatment cycle (28 days per cycle). The end-of-treatment (EOT) visit will be conducted within 7 days after the last dose or when the investigator decides to discontinue treatment. During the study period, the investigator and the sponsor may discuss and decide whether to stop exploring certain dose cohorts or to add exploration of other doses or dosing regimens based on the safety, PK and preliminary efficacy data obtained previously.

All subjects will undergo imaging evaluations of their tumors every 8 weeks until disease progression is confirmed by the investigator, the subject begins new antitumor therapy, dies, is lost to follow-up, or withdraws from the study, whichever occurs first.

Registry

clinicaltrials.gov

Start Date

May 19, 2024

End Date

January 31, 2028

Last Updated

last month

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Avistone Biotechnology Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female subjects, ≥18 years of age at the time of signing the informed consent form.
•Participants with a histologically confirmed diagnosis of unresectable locally advanced or metastatic solid tumors, relapsed or refractory to existing standard therapy, intolerant or unsuitable for existing standard therapy, or for whom no standard therapy is available (standard therapy is defined as therapy recommended by established guidelines and consensus \[including, but not limited to, chemotherapy, radiotherapy, targeted therapy based on mutation status, immunotherapy, and surgery\]). Locally advanced participants must be ineligible for radical surgery or radiotherapy. Participants who are intolerant of or unsuitable for existing standard therapy or for whom no standard therapy is available will be required to document these reasons.
•Documentary evidence of pathogenic MET alterations from a local laboratory accredited by the Clinical Laboratory Improvement Act Amendments (CLIA), the International Organization for Standardization/Independent Ethics Committee (ISO/IEC), the College of American Pathologists (CAP), or other equivalent accreditation. Part 1 Specific Inclusion Criteria: Subjects carrying pathogenic MET alterations (including MET mutations, MET amplification, MET overexpression, MET fusions) will be enrolled. Part 2 Specific Inclusion Criteria: Subjects will be enrolled into one of the following 5 cohorts based on tumor type, MET alteration status, and prior therapy. Cohort 1: Subjects must have pathologically confirmed, diagnosed NSCLC with a MET exon 14 jump mutation, with or without other MET alterations, and prior treatment with an approved MET-TKI (e.g., camatinib and topotecanib). Cohort 2: Subjects must have pathologically confirmed, diagnosed NSCLC with a MET exon 14 jump mutation, with or without other MET alterations, relapsed or refractory to platinum-based chemotherapy, or intolerant or unsuitable for platinum-based chemotherapy, and have not received a prior MET-TKI. Cohort 3: Subjects must have pathologically confirmed, diagnosed NSCLC with a MET amplification, no MET exon 14 jump mutation, relapsed or refractory to platinum-based agent chemotherapy, intolerant to platinum-based agent chemotherapy, or unsuitable for platinum-based agent chemotherapy. Cohort 4: Subjects must have pathologically confirmed, diagnosed solid tumors (other than NSCLC) with MET exon 14 jump mutations, with or without other MET alterations, relapsed or refractory to standard therapy, or intolerant or unsuitable for standard therapy, or no standard therapy available. Cohort 5: Subjects must have a pathologically confirmed, diagnosed solid tumor with MET amplification (except NSCLC) or overexpression or fusion, without MET exon 14 jump mutations, relapsed or refractory to standard therapy, or intolerant or unsuitable for standard therapy, or no standard therapy available.
•At least one measurable target lesion as defined by RECIST v1.1 (Appendix 3). (except for the low dose groups 7.5mg and 15mg).
•Part 1 ECOG PS ≤ 1; Part 2 ECOG PS ≤
•expected survival of ≥ 12 weeks in the judgment of the investigator.
•Good organ function as determined by medical evaluation (within 7 days prior to study treatment), including: Good hematologic status, defined as: absolute neutrophil count (ANC) ≥ 1.5 x 10 9/L, hemoglobin ≥ 90 g/L, and platelets ≥ 75 x 109/L. Receipt of platelet transfusions is not permitted within 3 days prior to testing, erythrocyte transfusions within 14 days prior to testing, and hematopoietic growth factors (polyethylene glycolized granulocyte colony-stimulating factor \[G-CSF\] or erythropoietin is within 14 days prior to testing) within 7 days prior to testing. Hematopoietic growth factors (polyethylene glycolated granulocyte colony-stimulating factor \[G-CSF\] or erythropoietin for up to 14 days prior to testing) are not allowed within days. Good hepatic function, defined as serum TBIL ≤ 1.5 x ULN (TBIL ≤ 3 x ULN with direct bilirubin ≤ 1.5 x ULN in subjects known to have Gilbert\'s syndrome), and serum ALT or AST ≤ 2.5 x ULN (or 5.0 x ULN in subjects with confirmed liver metastases). Good renal function, defined as creatinine clearance ≥ 50 mL/min (measured or calculated by the Cockcroft-Gault formula \[Appendix 4\]). Good coagulation function, defined as (including when receiving anticoagulation): prothrombin time (PT) \< 1.5 x ULN and activated partial thromboplastin time (APTT) \< 1.5 x ULN If subjects are receiving anticoagulation, they must have received a stable dose of anticoagulant for at least 1 month prior to study treatment.
•Female subjects should use adequate contraception until 90 days after EOT, should not be breastfeeding, and must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test within 7 days prior to initiation of dosing for female subjects of childbearing potential; female subjects of childless potential must meet one of the following criteria at screening: Postmenopausal defined as amenorrhea for at least 12 months after cessation of all exogenous hormone therapy (if applicable). applicable) followed by amenorrhea for at least 12 months. Irreversible surgical sterilization such as hysterectomy, bilateral salpingo-oophorectomy, or bilateral salpingo-oophorectomy (as opposed to tubal ligation) has been clearly documented.
•Male subjects whose female partners are of childbearing potential are required to use adequate contraception (i.e., barrier methods) during study participation and for 90 days after EOT. Male subjects must also refrain from sperm donation during study participation and for 90 days after the last dose of study treatment.
•Be able to provide signed informed consent and comply with the requirements and limitations outlined in the Informed Consent Form (ICF) and in this study.

Exclusion Criteria

•for dose extension only (Part 2): known major driver gene alterations other than MET. For example, NSCLC harboring targeted alterations such as EGFR, ALK, RET, ROS1, BRAF, KRAS, etc. Investigators should discuss enrollment with sponsors regarding co-mutations.
•Prior treatment with other type II MET-TKIs such as cabozantinib, glitinib, and melatinib (type II MET-TKIs are multi-targeted inhibitors that bind to the inactive conformation (DFG-out) of MET in the ATP pocket).
•Participation in another therapeutic clinical trial within 28 days prior to the first study dose.
•Received antineoplastic therapy (chemotherapy, immunotherapy, hormone therapy, targeted therapy, biologic therapy, or other antineoplastic therapy, except for hypothyroid hormone or estrogen replacement therapy, anti-estrogen analogs, or agonists required for suppression of serum testosterone levels) within 14 days or 5 half-lives (whichever is shorter) of the first dose of study treatment. The following exceptions apply: 1) Received nitrosourea or mitomycin C within 6 weeks prior to the first dose of study treatment. 2) Received a proprietary medicine with an antitumor indication within 7 days prior to the first dose of study treatment.
•has received wide-field radiotherapy within 28 days prior to the first dose of study treatment or has received palliative localized radiotherapy within 14 days prior to the first dose of study treatment. Subjects must have recovered from all radiotherapy-related toxicities and not require corticosteroids.
•Underwent major surgery (excluding diagnostic procedures) within 4 weeks prior to the initial study treatment, or is expected to require major surgery during the study period.
•Toxicity from prior therapy has not subsided to ≤ Grade 1 or baseline levels as evaluated by NCI-CTCAE v5.
•Note: For certain Grade 2 toxicities (e.g., alopecia, skin pigmentation, neuropathy), subjects may be enrolled if the toxicity is stable and does not compromise the safety of participation in this study.
•History of another primary solid tumor diagnosed or requiring treatment within the past 3 years (with the exception of localized basal cell or squamous cell carcinoma of the skin that has been adequately treated; or any other carcinoma in situ currently in complete remission).
•Presence of CNS metastases that are known to be symptomatic or clinically unstable or that require an increased steroid dose to manage central nervous system (CNS) symptoms within 4 weeks prior to the first study dose. Note: Subjects with symptomatic CNS metastases may be enrolled in the study after treatment and control of their symptoms provided they have been clinically stable for at least 2 weeks, have no evidence of new brain metastases or enlargement of brain metastases, and have not had an increase in steroid dose to manage CNS symptoms within 4 weeks prior to the first study dose. Persons with comorbid carcinomatous meningitis or meningeal spread or spinal cord compression were not eligible for enrollment, regardless of whether they were clinically stable.

Arms & Interventions

ANS014004

Dosage: 1. Dose-escalation participants receive ANS014004 single dose on Day 1, if DLT does not occur within the 7-day elution period, subjects will begin multiple doses on Day 8 and receive ANS014004 QD/BID for a 28-day cycle. 2, Backfill, Dose Extension Subjects, who go directly to multiple dosing, will receive ANS014004 QD/BID for 28 days as a cycle. Dosing Schedule: 1. Dose-escalation subjects, single dosing + multiple dosing, 35-day cycle. 2, Backfill, dose-expansion subjects, direct access to multiple dosing, 28 days to a cycle.

Intervention: ANS014004

Outcomes

Primary Outcomes

Proportion of patients with radiological response (ORR)

Time Frame: 2 years

Assessed by overall response rate (ORR) defined as the proportion of patients who have a confirmed complete or partial radiological response by the Investigator according to RECIST v1.1

Incidence of Serious Adverse Events (SAEs)

Time Frame: 2 years

Number of patients with serious adverse events by system organ class and preferred term

Incidence of baseline laboratory finding, ECG and vital signs changes

Time Frame: 2 years

measured by laboratory and vital sign variables over time including change from

Incidence of Adverse Events (AEs)

Time Frame: 2 years

Number of patients with adverse events by system organ class and preferred term

Incidence of dose-limiting toxicities (DLT) as defined in the protocol

Time Frame: 2 years

Number of patients with at least 1 dose-limiting toxicity (DLT), which is any toxicity defined as a DLT in the Clinical Study Protocol

Secondary Outcomes

Pharmacokinetics of ANS014004: Half-life(2 years)
Progression free Survival (PFS)(2 years)
Objective Response Rate (ORR)(2 years)
Duration of Response (DoR)(2 years)
Disease Control Rate (DCR)(2 years)
Overall Survival (OS)(2 years)
Pharmacokinetics of ANS014004: Area under the concentration time curve (AUC)(2 years)
Pharmacokinetics of ANS014004: Time to maximum plasma concentration of the study drug (T-max)(2 years)
Pharmacokinetics of ANS014004: Clearance(2 years)
Pharmacokinetics of ANS014004: Plasma PK concentrations(2 years)
Pharmacokinetics of ANS014004: Maximum plasma concentration of the study drug (C-max)(2 years)