Phase 1/2 Study of BBT-176 in Advanced NSCLC With Progression After EGFR TKI Treatment

Study Overview
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Brief Summary
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This clinical trial is the first-in-human study of BBT-176. The purpose of this trial is to investigate the safety and tolerability of BBT-176 (Part 1) and to evaluate the anti-tumor activity of BBT-176 (Part 2).

Official Title
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A Phase 1/2, Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of BBT-176 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Who Progressed Following Prior Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Agent

Conditions
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NSCLC

Intervention / Treatment
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* Drug: BBT-176


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Provision of signed and dated, written informed consent before any study specific procedures, sampling and analyses Histological or cytological confirmation of advanced and/or metastatic stage IIIB/IV NSCLC Radiological documentation of disease progression while on a previous continuous (at least 30 days) treatment with an EGFR TKI monotherapy (including, but not limited to, osimertinib, afatinib, gefitinib, or erlotinib) Patients must fulfill one of the following: Confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including, but not limited to, exon 19 deletion, L858R, or L861Q) Documented partial or complete response or a significant and durable stable disease (at least 6 months), based on the RECIST or WHO criteria, after treatment of an EGFR TKI Key Exclusion Criteria: Treatment with any of the following: An EGFR TKI, including but not limited to osimertinib, afatinib, gefitinib, or erlotinib within 8 days of the first dose of study treatment. Any cytotoxic chemotherapy, investigational agents, or anticancer drugs for the treatment of advanced NSCLC, between prior EGFR TKI treatment and BBT-176 treatment Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment Patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation within 6 weeks of the first dose of study treatment Any unresolved toxicities from prior therapy greater than NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) Grade 1 at the time of starting study treatment, with the exception of alopecia and Grade 2 neuropathy related to prior platinum-therapy Spinal cord compression or brain metastases, unless asymptomatic and stable

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: BBT-176<br> | Drug: BBT-176<br>* BBT-176 given orally alone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Part 1) Incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities (DLTs) | any toxicity not attributable to the disease or disease-related processes under investigation that occurs from the first dose of study treatment in dose-escalation cohorts as defined in the protocol. | 21 days from the first dosing | 
| (Part 2) Objective Response Rate (ORR) | ORR is estimated by the number of patients with a best overall response of CR or PR divided by the total number of patients who are evaluable for efficacy. | Every 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Part 1) PK parameters - peak concentration (Cmax) | Peak plasma concentration of BBT-176 | Up to Cycle 2 Day 1 (each cycle is 21 days) | 
| (Part 1) PK parameters - area under the concentration-time curve (AUC) | Area under the plasma concentration-time curve of BBT-176 | Up to Cycle 2 Day 1 (each cycle is 21 days) | 
| (Part 1) Objective Response Rate (ORR) | ORR is estimated by the number of patients with a best overall response of Complete Response (CR) or Partial Response (PR) divided by the total number of patients who are evaluable for efficacy. | Every 6 weeks, approximately 1 year | 
| (Part 2) Duration of Response (DoR) | DoR is calculated for every patient with a response to therapy (PR and CR) and is defined as the number of days from the date of initial response to the date of the first documented disease progression/relapse (including clinical progression) or death, whichever occurs first. | throughout study completion, approximately 1 year | 
| (Part 2) Incidence of Adverse Event (AE)s | Number of patients experiencing AEs | throughout study completion, approximately 1 year | 
| (Part 2) BBT-176 concentrations | Plasma BBT-176 concentrations at steady state | At Cycle 2 Day 1 (each cycle is 21 days) | 
| (Part 2) Progression Free Survival (PFS) | PFS will be calculated for each patient as the number of days from the first day of treatment to the date of the first documented disease progression or date of death, whichever occurs first. | throughout study completion, approximately 1 year |