Study of NGM831 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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Study of NGM831 as Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumors

Official Title
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A Phase 1/1b Dose Escalation/Expansion Study of NGM831 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumors

Conditions
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Pancreatic Cancer, Breast Cancer, Gastric Cancer, Non-small Cell Lung Cancer, Cervical Cancer, Endocervical Cancer, Squamous Cell Carcinoma of Head and Neck, Bladder Urothelial Cancer, Colorectal Carcinoma, Esophageal Cancer, Ovarian Cancer, Renal Cell Carcinoma, Prostate Cancer, Melanoma, Mesothelioma, Cholangiocarcinoma

Intervention / Treatment
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* Drug: NGM831
* Drug: NGM831 plus pembrolizumab
* Drug: NGM831


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically documented locally advanced or metastatic solid tumor malignancy. Adequate bone marrow, kidney and liver function Performance status of 0 or 1. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1 except for AEs not constituting a safety risk by Investigator judgement. Exclusion Criteria: •Prior treatment targeting ILT3.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NGM831 Monotherapy Dose Escalation<br>Part 1a Single Agent Dose Escalation | Drug: NGM831<br>* Drug: NGM831 NGM831 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.<br>|
| Experimental: NGM831 Combination Dose Finding with Pembrolizumab<br>Part 1b NGM831 plus pembrolizumab | Drug: NGM831 plus pembrolizumab<br>* Drug: NGM831 NGM831 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated. Drug: pembrolizumab Pembrolizumab will be administered intravenously (IV) every 3 weeks in a 21 day cycle.<br>|
| Experimental: NGM831 Monotherapy Dose Expansion<br>Part 2a Single Agent Dose Expansion | Drug: NGM831<br>* Drug: NGM831 Preliminary recommended phase 2 dose (RP2D) of NGM831 is given intravenously (IV) every 3 weeks in a 21 day cycle.<br>|
| Experimental: NGM831 Combination Dose Expansion Arm A<br>NGM831 plus pembrolizumab | Drug: NGM831 plus pembrolizumab<br>* Drug: NGM831 NGM831 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated. Drug: pembrolizumab Pembrolizumab will be administered intravenously (IV) every 3 weeks in a 21 day cycle.<br>|
| Experimental: NGM831 Combination Dose Expansion Arm B<br>NGM831 plus pembrolizumab | Drug: NGM831 plus pembrolizumab<br>* Drug: NGM831 NGM831 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated. Drug: pembrolizumab Pembrolizumab will be administered intravenously (IV) every 3 weeks in a 21 day cycle.<br>|
| Experimental: NGM831 Combination Dose Expansion Arm C<br>NGM831 plus pembrolizumab | Drug: NGM831 plus pembrolizumab<br>* Drug: NGM831 NGM831 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated. Drug: pembrolizumab Pembrolizumab will be administered intravenously (IV) every 3 weeks in a 21 day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients with Dose-limiting Toxicities (Part 1) | A DLT is defined as an AE that meets at least one of the criteria listed in protocol, according to National Cancer Institute (NCI) common terminology criteria for AE (CTCAE) version 5.0, and is considered by the Investigator to be clinically relevant and attributed to the study treatment during the first 21 days after the first dose of study treatment. | Baseline up to 21 Days | 
| Incidence of Adverse Events (Part 1 and Part 2) | Number of patients with treatment-emergent adverse events (AEs) An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of patients who experience at least one AE will be presented. | Baseline up to Approximately 24 months | 
| Number of Patients in Expansion Cohort with Objective Responses (Part 2) | Objective Response Rate is defined as the proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) divided by the total number of evaluable patients per RECIST v1.1 | Baseline up to Approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Serum Concentration (Cmax) of NGM831 (Part 1) | Cmax is defined as the observed maximum serum concentration post drug administration. Will be measured on Day 1, 2, 4, 8 and 15 of Cycles 1 and 3, Day 1 of Cycle 2 and Day 1 of Cycle 4 and each cycle thereafter | Baseline up to approximately 24 months | 
| Area Under the Curve (AUC) of Serum NGM831 (Part 1) | Area under the curve from time zero extrapolated to the last time point prior to the next dose. Will be measured on Day 1, 2, 4, 8 and 15 of Cycles 1 and 3, Day 1 of Cycle 2 and Day 1 of Cycle 4 and each cycle thereafter. | Baseline up to approximately 24 months | 
| Time to Maximum (Tmax) Observed Serum Concentration of NGM831 (Part 1) | Tmax is defined as the time to reach the observed maximum serum concentration (Cmax). Will be measured on Day 1, 2, 4, 8 and 15 of Cycles 1 and 3, Day 1 of Cycle 2 and Day 1 of Cycle 4 and each cycle thereafter. | Baseline up to approximately 24 months | 
| Half-life (t1/2) of NGM831 in Serum (Part 1) | Time measured for the serum concentration to decrease by one half during the terminal phase. Will be measured on Day 1, 2, 4, 8 and 15 of Cycles 1 and 3, Day 1 of Cycle 2 and Day 1 of Cycle 4 and each cycle thereafter. | Baseline up to approximately 24 months | 
| Systemic Clearance (CL) of NGM831 (Part 1) | CL is defined as systemic clearance. Will be measured on Day 1, 2, 4, 8 and 15 of Cycles 1 and 3, Day 1 of Cycle 2 and Day 1 of Cycle 4 and each cycle thereafter. | Baseline up to approximately 24 months | 
| Volume of Distribution (Vss) of NGM831 at Steady State (Part 1) | Vss is defined as the volume of distribution at steady state. Will be measured on Day 1, 2, 4, 8 and 15 of Cycles 1 and 3, Day 1 of Cycle 2 and Day 1 of Cycle 4 and each cycle thereafter. | Baseline up to approximately 24 months | 
| Anti-drug Antibodies (ADA) Against NGM831 (Part 1 and Part 2) | Incidence and titers of anti-drug antibodies (ADA) against NGM831. Will be measured on Day 1 of each cycle. | Baseline up to approximately 24 months | 
| Neutralizing antibodies (nAB) against NGM831 (Part 1 and Part 2) | Incidence and titers of neutralizing antibodies (nAB) against NGM831. Will be measured on Day 1 of each cycle. | Baseline up to approximately 24 months | 
| Number of Patients with Objective Responses (Part 1) | Objective Response Rate is defined as the proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) divided by the total number of evaluable patients per RECIST v1.1 | Baseline up to approximately 24 months | 
| Trough Concentrations of NGM831 (Part 2) | Trough Concentration refers to the serum concentration of NGM831 observed just before treatment administration. Will be measured on Day 1, 2, 4, 8 and 15 of Cycles 1 and 3, Day 1 of Cycle 2 and Day 1 of Cycle 4 and each cycle thereafter. | Baseline up to approximately 24 months |