To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of ABN401 in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer Harboring c-MET Dysregulation

NCT04052971 | Completed Phase 1 DMC

• 1 other identifier: ABN401-001
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 7

Brief Summary

This is a dose escalation, Phase 1 study of ABN401 in patients with advanced solid tumors, refractory metastatic disease, or refractory locally advanced disease not amenable to local therapy.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• To evaluate the safety and tolerability of ABN401.

  Safety and tolerability determined by abnormal clinical laboratory tests, vitals signs, physical exam, ECG parameters, Liver function tests

  Measurements at Baseline till the last day of Visit

• To determine the objective response rate (ORR) to ABN401 according to RECIST 1.1

  Objective response rate (ORR) is defined as the proportion of patients who experience a complete response (CR) or partial response (PR) as measured by RECIST 1.1.

  Up to 30 days

Secondary Outcomes (5)

• To determine the systemic PK of ABN401.

  Dose Escalation Phase: Cycle 1- Day 1, Day 2, Day 5, Day 8, Day 15; Dose Expansion Phase: Cycle 1, Day -2, Day 1, Day 2, Day 8, Day 15

• To determine preliminary estimate of ABN401 efficacy in patients with selected malignancies

  Screening and at every 6 weeks from C1D1 independent of cycle length

• Evaluate the duration of response (DoR) to ABN401 according to RECIST 1.1

  Up to 30 days

• Assess the objective disease control rate (DCR) of ABN401 according to RECIST 1.1

  Up to 30 days

• Determine progression free survival (PFS) according to RECIST 1.1

  Up to 30 days

Study Arms (2)

Escalation phase

EXPERIMENTAL

Drug: ABN401 Route of Administration: Oral The study will follow a single patient cohort approach for the first 3 regular dose levels followed by classic 3+3 design. The starting dose is 50mg QD.

Drug: ABN401- Escalation Phase

Expansion phase

EXPERIMENTAL

Drug: ABN401 Route of Administration: Oral Once the maximum tolerated dose (MTD) or highest escalation cohort has been reached, or notable efficacy has been observed at a given dose level, a decision as to Recommended Phase 2 dose (RP2D) will be determined. Up to 40 patients with Non-Small Cell Lung Cancer Harboring c-MET Dysregulation will be recruited.

Drug: ABN401- Expansion Phase

Interventions

ABN401- Escalation Phase DRUG

Dose administration: Escalation Phase The regular dose levels of ABN401 will range from 50 mg to 1800 mg QD daily for 21 days.

Escalation phase

ABN401- Expansion Phase DRUG

Dose administration: Expansion Phase The expansion phase of the study will use the dose and schedule determined to be most appropriate in the dose escalation portion of the study. This may be the MTD and/or the RP2D and will consist of cohorts of NSCLC patients with c-MET dysregulation. Patients will receive ABN401 800 mg, administered orally once daily for 21 days until disease progression, unacceptable toxicity, or patient withdrawal.

Expansion phase

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent before any study-specific screening procedures.
• Male or female ≥ 18 years of age or designated age of majority according to regulatory authorities, whichever is higher.
• Body weight ≥ 40 kg and ≤ 110 kg.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS), 0 or 1.
• Diagnosis:
• For the Phase 1 dose escalation, must have:
• Histological or cytological diagnosis of melanoma or any type of carcinoma or sarcoma,
• Refractory metastatic disease, or refractory locally advanced disease not amenable to local therapy,
• Metastatic breast or prostate cancer may have bone-only disease.
• For the Phase 1 extension (pilot expansion), patients must have NSCLC with c-MET overexpression, MET amplification, or MET exon 14 skipping by local biomarker assessment as defined in study protocol. The number of patients with only c-MET overexpression is limited to 50% of enrolled patients in that dosing cohort including escalation and extension.
• Progressive disease:
• a. Phase 1: 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.
• At least one measurable lesion per response evaluation criteria in solid tumors (RECIST) 1.1, with the exception of bone-only disease (i.e., non-measurable disease per RECIST 1.1) with at least 1 radiological non-target lesion.
• 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:
• 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,

You may not qualify if:

• Previous severe hypersensitivity reaction to any component of ABN401.
• Prior therapy:
• a. Phase 1: 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,
• Genetic analysis:
• a. Phase 1 Extension Cohort, existing data by genetic analysis of the patient's tumor tissue that may result in an increased probability of being resistant to c-MET inhibitors, including 1) EGFRi; 2) ALKi; 3) ROSi; 4) BRAFi; 5) NTRKi; 6) RETi,
• 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).
• Prior organ or stem cell transplant.
• Known active infection with HIV, HTLV-1, hepatitis B virus (HBV), or hepatitis C virus (HCV):
• Patients with a history of hepatitis B or C are allowed if HBV DNA or HCV RNA are undetectable,
• 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.
• Symptomatic ascites or pleural effusion, unless clinically stable for at least two weeks following treatment for these conditions (including therapeutic thoraco- or paracentesis).
• Known active 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.
• 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 non-melanoma skin cancer, superficial bladder cancer, in situ cervical cancer, or other in situ cancers.
• 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's judgement.
• 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.

Sponsors & Collaborators

• Abion Inc: lead
• Novotech (Australia) Pty Limited: collaborator

Study Sites (7)

ST George Private Hospital

Kogarah, New South Wales, 2217, Australia

Location

Sydney Southwest Private Hospital

Liverpool, New South Wales, 2170, Australia

Location

Scientia Clinical Research

Randwick, New South Wales, 2031, Australia

Location

Linear Clinical Research

Perth, Western Australia, 6009, Australia

Location

National Cancer Centre

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

Yonsei University Health System, Severance

Seoul, 03722, South Korea

Location

Asan Medical Centre

Seoul, 05505, South Korea

Location

Related Links

• Related Info

Study Design

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

Study Record Dates

• First Submitted: July 26, 2019
• First Posted: August 12, 2019
• Study Start: August 1, 2019
• Primary Completion: November 30, 2023
• Study Completion: January 3, 2024
• Last Updated: January 6, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3); AU (4)