A Study of NB004 as Monotherapy or Combination Therapy in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a Phase 1, Open-label, Multicenter Study to Assess the Safety, Tolerability, and Pharmacokinetics of NB004 Administered as Monotherapy or Combination Therapy in Subjects with Advanced Solid Tumors

Detailed Description
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This study is a Phase 1, open-label, multicenter study of NB004 administered orally in patients with histologically and/or cytologically confirmed diagnosis of advanced solid tumors that are metastatic for which all standard treatment options have been given and are ineffective, or is no longer eligible for additional standard treatment options. The study is comprised of a dose escalation phase to determine the maximum tolerated dose and the RP2D and an expansion phase to further explore the safety and preliminary antitumor activity of NB004.

Official Title
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A Phase 1, Open-label, Multicenter Study to Assess the Safety, Tolerability, and Pharmacokinetics of NB004 Administered as Monotherapy or Combination Therapy in Subjects With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: NB004 tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: males or females of any race>(=)18 years age. Histologically and/or cytologically confirmed diagnosis of advanced solid tumors that are without standard treatment options (part 1). Pathologically confirmed locally advanced or metastatic solid tumors with KRAS G12C mutation as determined by a test that has been approved by FDA or local health authority (part 2&3). Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Life expectancy>(=)12 weeks. Adequate organ and marrow function. Measurable or evaluable disease. Exclusion Criteria: Prior anti-cancer therapy within 2 weeks or at least 5 half-lives, whichever is longer, up to a maximum of 3 weeks, before the first dose. Toxicities from previous anti-cancer therapy that have not recovered as required. Brain metastatic disease, spinal cord compression, or leptomeningeal carcinomatosis. Active infection including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV): Female subjects who are pregnant, or breastfeeding, or planning to become pregnant while in this study or within 3 months after the last dose. Male subjects who plan to father a child while enrolled in the study or within 3 months after the last dose. Received prior treatment with a PIM kinase inhibitor.

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: NB004<br>Part1: Dose escalation phase of study drug NB004 monotherapy: Part 2: Dose Escalation Phase for the NB004 in combination with Sotorasib: Part 3: COMBO Dose Expansion Phase for the NB004 in combination with Sotorasib: | Drug: NB004 tablets<br>* Part1: Dose escalation phase of study drug NB004 monotherapy: Drug: NB004 tablets NB004 tablets will be administered orally once daily for repeated 28-day cycles until discontinuation criteria are met. Part 2: Dose Escalation Phase/ COMBO Dose Expansion Phase for the NB004 in combination with Sotorasib: Drug: NB004 tablets & Sotorasib NB004 tablets will be administered orally once a daily for repeated 21-day cycles until discontinuation criteria are met. Sotorasib will be administered with the recommended dosage per prescribing information approved by the FDA Part 3: Dose Escalation Phase/ COMBO Dose Expansion Phase for the NB004 in combination with Sotorasib: Drug: NB004 tablets & Sotorasib NB004 tablets will be administered orally once daily for repeated 21-day cycles until discontinuation criteria are met. Sotorasib will be administered with the recommended dosage per prescribing information approved by the FDA .<br>* Other names: Sotorasib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicities----Part 1/2 | Dose-limiting toxicities will be reviewed as a subset of adverse events that occurs within the first 28 days of dosing and meet protocol-specified criteria. | When subject complete 1 cycle (28 days) treatment with safety and tolerability assessment by investigators. | 
| Incidence of adverse events----Part 1/2 | An adverse event is any untoward medical occurrence in a participant who received study drug without regard to causal relationship. | Approximately 24 months since the first subject enrolled | 
| Objective Response Rate (ORR) ----Part 3 | Objective Response Rate (ORR) is defined as the percentage of patients whose efficacy is confirmed as complete response (CR) or partial response (PR) | [Time Frame: Approximately 24 months since the first subject enrolled] | 
| Duration of Response (DOR) ----Part 3 | DOR is defined as the time from the date of first documented response until date of documented progression, for subjects who achieve CR or PR. | [Time Frame: Approximately 24 months since the first subject enrolled] | 
| Time to Response (TTR) ----Part 3 | TTR is defined as the time interval between the date of first administration and the date of the first recording of response. At the same time, the initial response time and the time to best response will be calculated. | [Time Frame: Approximately 24 months since the first subject enrolled] | 
| Progression-free Survival (PFS) ----Part 3 | PFS is defined as the time from the date of the first dose until the date of disease progression, as defined by RECIST v1.1, or death. | [Time Frame: Approximately 24 months since the first subject enrolled] | 
| Clinical Benefit Rate (CBR) ----Part 3 | CBR is defined as the number of subjects with CR or PR or with SD maintained ≥24 weeks (as assessed by the Investigator, using RECIST v1.1) divided by the number of subjects in the analysis. Subjects without a postbaseline tumor assessment will be considered as having no clinical benefit. | [Time Frame: Approximately 24 months since the first subject enrolled] | 
| Overall survival (OS) ----Part 3 | OS is defined as the time from treatment start with study drug until event of death due to any cause. | [Time Frame: Approximately 24 months since the first subject enrolled] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax)----Part 1 | Maximum observed plasma concentration (Cmax) | Approximately 24 months since the first subject enrolled | 
| Time to Cmax (Tmax)----Part 1 | Time to Cmax (Tmax) | Approximately 24 months since the first subject enrolled | 
| Area under the curve (AUC) from time zero to the last measurable concentration AUC (0-t) ----Part 1 | AUC (0-t) = Area under the serum concentration versus time curve from time zero (pre-dose) to the time of the last | Approximately 24 months since the first subject enrolled | 
| Terminal elimination half life----Part 1 | Terminal elimination half life | Approximately 24 months since the first subject enrolled | 
| Objective Response Rate (ORR)----Part 2 | Objective Response Rate (ORR) is defined as the percentage of patients whose efficacy is confirmed as complete response(CR) or partial responses(PR) | Approximately 24 months since the first subject enrolled | 
| Duration of Response(DOR)----Part 2 | DOR is defined as the time from the date of first documented response until date of documented progression, for subjects who achieve CR or PR. | Approximately 24 months since the first subject enrolled | 
| Clinical Benefit Rate (CBR) ----Part 2 | CBR is defined as the number of subjects with CR or PR or with SD maintained ≥24 weeks (as assessed by the Investigator, using RECIST v1.1) divided by the number of subjects in the analysis. Subjects without a postbaseline tumor assessment will be considered as having no clinical benefit. | [Time Frame: Approximately 24 months since the first subject enrolled] | 
| Time to Response (TTR) ----Part 2 | TTR is defined as the time interval between the date of first administration and the date of the first recording of response. At the same time, the initial response time and the time to best response will be calculated. | [Time Frame: Approximately 24 months since the first subject enrolled] | 
| Progression-free Survival (PFS) ----Part 2 | PFS is defined as the time from the date of the first dose until the date of disease progression, as defined by RECIST | [Time Frame: Approximately 24 months since the first subject enrolled] | 
| Overall survival (OS) ----Part 2 | OS is defined as the time from treatment start with study drug until event of death due to any cause | [Time Frame: Approximately 24 months since the first subject enrolled] |