To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of ABN401 in Patients With Advanced Solid Tumors
- Conditions
- Neoplasms
- Registration Number
- KCT0004583
- Lead Sponsor
- Abion
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 84
1. Only patients who meet all of the inclusion criteria and none of the exclusion criteria, as confirmed by the medical monitor at screening/day 1 of first dosing, will be eligible to receive ABN401. Signed informed consent before any study-specific screening procedures.
2. Male or female = 18 years of age or designated age of majority according to the regulatory authorities, whichever is higher.
3. Body weight = 40 kg and = 110 kg.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS), 0 or 1.
5. Diagnosis:
a. For the Phase 1 dose escalation, must have:
1) Histological or cytological diagnosis of melanoma or any type of carcinoma or sarcoma,
2) Refractory metastatic disease, or refractory locally advanced disease not amenable to local therapy,
3) Metastatic breast or prostate cancer may have bone-only disease.
b. For the Phase 1 extension (pilot expansion), must have NSCLC with cMET overexpression, MET amplification, or MET exon 14 skipping by
local biomarker assessment as defined and categorized in Section
6.3.4.1. The number of patients with only c-MET overexpression is limited to 50% of enrolled patients in that dosing cohort including escalation and extension.
6. Progressive disease:
Progressive disease on established standard medical anti-cancer therapy for his/her tumor type or intolerant to such therapy, or in the opinion of the investigator considered ineligible for a particular form of standard therapy on medical grounds.
7. At least one measurable lesion per response evaluation criteria in solid tumors (RECIST) 1.1, with the exception of bone-only disease (i.e., nonmeasurable disease per RECIST 1.1) with at least 1 radiological non-target lesion.
8. If not menopausal or surgically sterile, willing to practice at least one of the following highly effective methods of birth control for at least a (partner’s) menstrual cycle before and for 3 months after study drug administration:
a. True abstinence, when this is in line with the preferred and usual lifestyle of the patient, from sexual intercourse with a member of the opposite sex,
b. Sexual intercourse with vasectomized male/sterilized female partner,
c. Hormonal female contraceptive (oral, parenteral, intravaginal, implantable, or transdermal) for at least 3 consecutive months prior to investigational product administration (when not clinically contraindicated as in breast, ovarian and endometrial cancers),
d. Use of an intrauterine contraceptive device.
9. Resolution of prior-therapy-related AEs (including immune-related AEs but excluding alopecia) to = Grade 1 per CTCAE, and no treatment for these AEs for at least 2 weeks prior to the time of enrollment. Alopecia, sensory neuropathy Grade = 2, or other Grade = 2 AEs not constituting a safety risk based on investigator’s judgment are acceptable.
10. Minimum of 2 weeks since last dose of hormone therapy.
11. Minimum of > 2 weeks or > 5 half-lives (whichever is longer) between the start of study treatment since last dose of radiotherapy, chemotherapy or molecularly targeted agents or tyrosine kinase inhibitors; minimum of > 3 weeks of the start of study treatment since last dose of immunotherapy /monoclonal antibodies; > 6 weeks of the start of study treatment since the last dose of nitrosoureas, antibody-drug conjugates or radioactive isotopes.
12. Adequate organ function as indicated by the following laboratory values:
System Laboratory Value
Hematological:
Neutrophils
Only patients who do not meet any of the following criteria, as confirmed by the medical monitor at screening/day 1 of first dosing, will be permitted to start
study treatment.
1. Previous severe hypersensitivity reaction to any component of ABN401. (The components are listed in Table 7).
2. Prior therapy
Treatment with more than 4 lines of prior systemic therapy for recurrent/metastatic disease. If the patient was treated with more than 4 lines but his/her condition is eligible to participate to the trial by the investigator’s judgement, the patient might be able to be enrolled to the trial under the medical monitor and the sponsor’s approval.
3. Genetic analysis:
Phase 1 Extension (pilot expansion) Cohort (s): existing data by genetic analysis of the patients tumor tissue that may result in an increased probability of being resistant to c-MET inhibitors, including 1) EGFR; 2) ALK; 3) ROS; 4) BRAF; 5) NTRK; 6) RET.
4. Chronic inflammatory liver condition. History or clinical evidence of any liver or biliary pathology including cirrhosis, infectious disease, inflammatory conditions, steatosis, or cholangitis (including ascending cholangitis, primary sclerosing cholangitis, obstruction, perforation, fistula of biliary tract, spasm of sphincter of Oddi, biliary cyst or biliary atresia).
5. Prior organ or stem cell transplant.
6. Known active infection with HIV, HTLV-1, hepatitis B virus (HBV), or hepatitis C virus (HCV):
a. Patients with a history of hepatitis B or C are allowed if HBV DNA or HCV RNA are undetectable,
b. Active infection with human immunodeficiency virus (HIV) and CD4+T-cell count <350/µL. Patients not on established ART for at least four weeks and having a detectable HIV viral load.
7. Symptomatic ascites or pleural effusion, unless clinically stable for at least two weeks following treatment for these conditions (including therapeutic thoraco- or paracentesis).
8. Known active central nervous system (CNS) primary tumor or metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to first dose of study drug, have no evidence of new or enlarging brain metastases and are off steroids for at least 15 days prior to first dose of study drug.
9. Known history of a hematologic malignancy, malignant primary brain tumor, or of a second malignant primary solid tumor (other than that under study), unless the patient has undergone potentially curative therapy with no evidence of that disease for 3 years.
Note: The time requirement for no evidence of disease for 3 years does not
apply to patients who underwent successful definitive resection of nonmelanoma skin cancer, superficial bladder cancer, in situ cervical cancer, or other in situ cancers.
10. Active infection requiring therapy. However, subject with minor infections where oral antibiotic required, (e.g., urinary tract infection, Upper respiratory tract infection, etc.) could be eligible based on investigator’sjudgement.
11. Use of systemic corticosteroids > 10 mg/day prednisone or equivalent within 30 days or other immunosuppressive drugs within 30 days prior to first drug administration.
12. Received an investigational product or treated with an investigational device within 30 days prior to first drug administration.
13. Has been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents or tyrosine kinase inhibitors within
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Tolerance and toxicity of ABN401 will be assessed through evaluation of physical examinations, vital signs, laboratory parameters, ECGs, solicited and unsolicited AEs including DLTs, and all causes of mortality.
- Secondary Outcome Measures
Name Time Method Response Criteria - Evaluation of Target Lesions/Evaluation of Non-target Lesions;Pharmacokinetic Endpoints -Standard Pharmacokinetic Analysis;Pharmacokinetic Endpoints- Exploratory biomarkers of archival or new biopsy tumor tissue