Phase 1b/2 Study to Evaluate ABT-101 in Solid Tumor and NSCLC Patients

Study Overview
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Brief Summary
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A Phase 1b/2, open-label, multicenter study to determine the recommended phase 2 (RP2D) of ABT-101in solid tumor and to explore the preliminary antitumor activities of ABT101 in patients with HER 2 mutated non-small cell lung cancer (NSCLC)

Detailed Description
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This study will be conducted in two parts: Part 1: Dose- Escalation, Phase 1b, is designed to determine the RP2D. Patients with solid tumor will be enrolled into a dose finding study scheme with the assessment of dose-limiting toxicities (DLTs). DLT assessment will be conducted during treatment cycle Part 2: Dose- Expansion, Phase 2, will evaluate the safety and efficacy of ABT-101 at the dosage and dosing regime determined in Phase 1b. Phase 2 will enroll NSCLC patients with HER2 mutations Study participation for all patients includes screening period, treatment period and safety/ follow-up period. Patient will received study treatment until progressive disease or any other discontinuation or withdrawal criterion is met

Official Title
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A Phase Ib/II, Open-Label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ABT-101 in Patients With Advanced Solid Tumors and HER2 Exon 20 Insertions Mutated Non- Small Cell Lung Cancer

Conditions
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Advanced Solid Tumor, Non Small Cell Lung Cancer, HER2 Mutations

Intervention / Treatment
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* Drug: ABT-101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged ≥ 20 years or adult age as per local regulations, at time of informed consent Histologically or cytologically confirmed advanced solid tumor (Part 1) or NSCLC with HER2 mutations as determined by the central result (Part 2) For patient in Part 2 only: Patients has measurable disease per RECIST 1.1 criteria Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Part 1), 0 to 2 (Part 2) Appropriate candidate for experimental therapy Adequate organ function Exclusion Criteria: Known active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis Serious acute or chronic infections Received a live-virus vaccination Received prior anticancer or other investigational therapy within 28 days or 5× the half-life prior to the first dose. Not recovered from prior- treatment toxicities to Grade ≤1 Major surgery within 28 days prior to the study treatment Concurrent malignancy within 2 years prior to first dose History or presence of clinically relevant cardiovascular abnormalities. QTcF) ≥ 470 ms Significant gastrointestinal disorder(s) that could interfere with absorption of ABT101 Known to have a history of alcoholism or drug abuse

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABT-101<br>Part 1- dose-escalation: ABT101 in patient with advanced cancer disease Part 2- dose expansion: ABT101 in patients with NSCLC with confirmed HER2 mutations | Drug: ABT-101<br>* Patients will receive ABT-101 by oral administration on a 28 days cycle<br>* Other names: DBPR112;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the recommended Phase 2 Dose (RP2D) of ABT101 in Part 1 | Determine the maximum tolerated dose (MTD) and RP2D of ABT101 based on Dose Limiting Toxicities | 12 months | 
| Determine antitumor activity based on Objective Response Rate (ORR) in Part 2 in patients with NSCLC with targeted mutation | Patients response according to RECIST 1.1 | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) ABT-101 | Plasma concentration of ABT101 | 48 months | 
| Area under the plasma concentration time curve (AUC) of ABT101 | Measure of AUC | 48 months | 
| Duration of response (DOR) | DOR is defined as the length of time between first response and the date of objectively documented progression of disease or death | 48 months | 
| Progression- free survival (PFS) | Measure of the time from study entry to disease progression or death due to any cause | 36 months | 
| Overall survival (OS) | Measure of overall survival | 36 months | 
| Objective response rate (ORR) in Part 1 | Objective response rate as determined by RECIST 1.1 | 12 months | 
| Number of patients with treatment-emergent adverse events as assessed by CTCAE v5.0 | Evaluate safety and tolerability of futibatinib in combination with binimetinib based on treatment-emergent adverse events per CTCAE v5.0(including serious adverse events),clinical laboratory parameters, ECGs, and vital signs | 48 months | 
| Disease control rate (DCR) | DCR is defined as the percentage of patients who have achieved a CR, PR, or SD. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ABT-101, NSCLC, HER2 Mutations