Trial Title:
A Study to Evaluate ANS014004 in Subjects With Locally Advanced or Metastatic Solid Tumors
NCT ID:
NCT06328439
Condition:
Locally Advanced or Metastatic Solid Tumors
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
Cohort1: 7.5mg Cohort2: 15mg Cohort3: 30mg Cohort4: 45mg Cohort5: 60mg
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
ANS014004
Description:
Specification: 7.5mg; 30mg QD Oral
Arm group label:
ANS014004
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 part (Part 1) will consist of a single-dose period and a
multiple-dose period (28 days per cycle), participants during dose escalation will
receive a single dose of ANS014004 on Day 1 of the single-dose period in order to
obtain complete PK parameters for the single dose. There will be a 7-day washout
period between the single dosing period and the multiple dosing period at the same
dose level. If no dose-limiting toxicity (DLT) occurs during the 7-day washout
period, participants will begin Cycle 1 (28 days per cycle) multiple dosing
treatment on Day 8, receiving ANS014004 once daily (QD). participants in the
backfill cohort will enter the multiple dosing period directly. The specific dose
which participant receives will depend on the different cohort assignments. The
dose-escalation part (Part 1) will use the initial accelerated titration design
(ATD) and the traditional "3 + 3" design to determine the MTD of ANS014004 in
subjects with locally advanced or metastatic solid tumors.
2. In the Dose Expansion (Part 2), participants, will receive oral administration
of ANS014004 QD at each treatment cycle (28 days per cycle). An
end-of-treatment (EOT) visit will be conducted within 7 days of the final dose
or investigator decision to discontinue.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female subjects, ≥18 years of age at the time of signing the informed
consent form.
2. 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.
3. 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.
4. At least one measurable target lesion as defined by RECIST v1.1 (Appendix 3).
(except for the low dose groups 7.5mg and 15mg).
5. Part 1 ECOG PS ≤ 1; Part 2 ECOG PS ≤ 2.
6. expected survival of ≥ 12 weeks in the judgment of the investigator.
7. 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.
8. 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.
9. 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.
10. 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:
1. 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.
2. 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).
3. Participation in another therapeutic clinical trial within 28 days prior to the
first study dose.
4. 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.
5. 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.
6. major surgery (other than diagnostic surgery) within 4 weeks prior to the first
study treatment or expected to require major surgery during the study period.
7. Toxicity from prior therapy has not subsided to ≤ Grade 1 or baseline levels as
evaluated by NCI-CTCAE v5.0. 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.
8. 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).
9. 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.
10. The subject is receiving an unstable or escalating dose of corticosteroids. For
subjects receiving corticosteroids for endocrine defects or disease-related symptoms
(excluding CNS disease), the dose must have been stabilized (or lowered) for at
least 14 days prior to the first dose of study treatment.
11. the presence of any evidence of severe or uncontrolled systemic disease, as judged
by the investigator, including, but not limited to: uncontrolled hypertension,
defined as a systolic blood pressure (BP) ≥160 mmHg or diastolic BP ≥100 mmHg
despite medication. for subjects with a history of hypertension, enrollment is
permitted if the BP is stable and is controlled within these limits with
antihypertensive therapy. Prior history of, or current clinical symptoms of,
interstitial lung disease or interstitial pneumonia, or high risk of interstitial
lung disease or interstitial pneumonia, including radiation pneumonitis (i.e.,
interfering with activities of daily living or requiring therapeutic intervention).
Unstable or decompensated respiratory and renal disease, active bleeding disorders.
12. Serious cardiovascular or cerebrovascular disease including, but not limited to:
Mean Fridericia formula-corrected QT intervals (QTcF) > 470 ms obtained on three
repetitions of 12-lead electrocardiograms (ECGs) at rest Symptomatic heart failure
with a New York Heart Association (NYHA) cardiac function classification of class II
or higher. Echocardiographic (ECHO) assessment showing a baseline left ventricular
ejection fraction (LVEF) below the lower limit of institutional normal (LLN) or <
50%. Any clinically significant rhythmic, conduction, or morphologic abnormality as
demonstrated by resting ECG results, e.g., complete left bundle branch block,
third-degree heart block, ventricular arrhythmia requiring antiarrhythmic therapy.
Any of the following within 6 months prior to the first dose of study treatment:
myocardial infarction, severe/unstable angina, coronary artery bypass grafting,
congestive heart failure, cardiomyopathy, pulmonary embolism, cerebral vascular
accident, or transient ischemic attack.
13. Presence of uncontrolled co-infections including, but not limited to: active
hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. If hepatitis B surface
antigen (HBsAg) positive, HBV DNA testing should be performed. Subjects may be
eligible to participate in the study if HBV DNA is <500 IU/ml or if the test
value is below the lower limit of detection at the study center. (Subjects with
primary liver cancer may be eligible for enrollment if HBV DNA <2000IU/ml) If HCV
antibody is positive, HCV ribonucleic acid (RNA) testing should be performed. If HCV
RNA is negative, the subject may be eligible for the study. Known human
immunodeficiency virus (HIV) infection or known history of acquired immunodeficiency
syndrome (AIDS), HIV positive. Active tuberculosis infection. Active infection
requiring systemic therapy that occurred within 14 days prior to the first dose of
study treatment.
14. Unwillingness or inability to comply with oral drug administration requirements or
the presence of gastrointestinal disorders such as refractory nausea and vomiting,
any acute or chronic gastrointestinal disorder, inability to swallow preparations,
or previous major colectomy may prevent adequate absorption of ANS014004.
15. Combined use of a potent P-glycoprotein (P-gp)/breast cancer resistance protein
(BCRP) inhibitor or a sensitive substrate of P-gp/BCRP or a drug metabolized by
CYP2B6/CYP2C9/CYP2C19/OCT2/OATP1B1/MATE1 within 5 half-lives prior to the use of
study treatment. For dose-escalation component only: Treatment with intermediate or
potent CYP2C8/CYP2D6/CYP3A4 inducers or inhibitors that cannot be replaced or
discontinued.
16. Combined use of acid-regulating drugs (e.g., proton pump inhibitors [PPIs] and H2
blockers) within 5 half-lives prior to use of study treatment.
17. Presence of pleural effusion, pericardial effusion or ascites requiring drainage
and/or causing severe clinical symptoms (e.g., causing shortness of breath,
tachycardia, etc.).
18. Previous or ongoing severe retinopathy.
19. History of allergic reaction to ANS014004 or its excipients, or to drugs with a
similar chemical or biological structure or class to ANS014004.
20. received any live attenuated vaccination within 30 days prior to the first dose of
study treatment.
21. known to have a psychiatric or substance abuse disorder that may affect the
subject's compliance with the study.
22. The subject has a pre-existing or persistent clinically significant disease, medical
condition, surgical history, abnormal physical examination findings, or laboratory
tests that, in the opinion of the investigator, are not in the best interest of the
subject; or may alter the absorption, distribution, metabolism, or excretion of the
study treatment; or impair the assessment of the study results.
23. unwillingness or inability to comply with the study procedures and study limitations
or which, in the investigator's judgment, would make the subject unsuitable for
participation in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Shanghai Chest Hospital
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Shun Lu, Ph.D
Phone:
+8618017321551
Email:
shunlu_shchest@sina.com
Start date:
March 19, 2024
Completion date:
January 31, 2028
Lead sponsor:
Agency:
Avistone Biotechnology Co., Ltd.
Agency class:
Industry
Collaborator:
Agency:
Shanghai Chest Hospital
Agency class:
Other
Collaborator:
Agency:
Hunan Cancer Hospital
Agency class:
Other
Collaborator:
Agency:
Henan Cancer Hospital
Agency class:
Other
Collaborator:
Agency:
Zhejiang Cancer Hospital
Agency class:
Other
Collaborator:
Agency:
Peking University Cancer Hospital & Institute
Agency class:
Other
Source:
Avistone Biotechnology Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06328439
