Study of NGM707 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies

Study Overview
=================
Brief Summary
-----------------
Study of NGM707 as Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies

Official Title
-----------------
A Phase 1/2 Dose Escalation/Expansion Study of NGM707 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies

Conditions
-----------------
Mesothelioma, Glioblastoma, Renal Cell Carcinoma, Non Small Cell Lung Cancer, Melanoma, Pancreatic Ductal Adenocarcinoma, Gastric Cancer, Squamous Cell Carcinoma of Head and Neck, Cholangiocarcinoma, Breast Cancer, Ovarian Cancer, Cervical Cancer, Endocervical Cancer, Colorectal Cancer, Esophageal Cancer

Intervention / Treatment
-----------------
* Drug: NGM707
* Drug: NGM707 plus pembrolizumab
* Drug: NGM707
* Drug: NGM707
* Drug: NGM707
* Drug: NGM707 plus pembrolizumab
* Drug: NGM707 plus pembrolizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically documented locally advanced or metastatic solid tumor malignancy. Progressed or was intolerant to all available therapies known to confer clinical benefit appropriate for their tumor type, and for which the patient was eligible and willing to receive, or refused SOC treatments that are perceived to have marginal clinical benefit. 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 ILT2 and/or ILT4 or targeting HLA-G.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NGM707 Monotherapy Dose Escalation<br>Part 1a Single Agent Dose Escalation | Drug: NGM707<br>* Drug: NGM707 NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.<br>|
| Experimental: NGM707 Combination Dose Finding with pembrolizumab<br>Part 1b NGM707 plus pembrolizumab | Drug: NGM707 plus pembrolizumab<br>* Drug: NGM707 NGM707 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: NGM707 Monotherapy Dose Expansion Arm A<br>NGM707 in RCC | Drug: NGM707<br>* Drug: NGM707 Preliminary recommended phase 2 dose (RP2D) of NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle.<br>|
| Experimental: NGM707 Monotherapy Dose Expansion Arm B<br>NGM707 in CRC | Drug: NGM707<br>* Drug: NGM707 Preliminary recommended phase 2 dose (RP2D) of NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle.<br>|
| Experimental: NGM707 Monotherapy Dose Expansion Arm C<br>NGM707 in Ovarian Cancer | Drug: NGM707<br>* Drug: NGM707 Preliminary recommended phase 2 dose (RP2D) of NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle.<br>|
| Experimental: NGM707 Combination Dose Expansion Arm E<br>NGM707 with pembrolizumab in NSCLC | Drug: NGM707 plus pembrolizumab<br>* Drug: NGM707 Preliminary recommended phase 2 dose (RP2D) of NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle. Drug: pembrolizumab Pembrolizumab will be administered intravenously (IV) every 3 weeks in a 21 day cycle.<br>|
| Experimental: NGM707 Combination Dose Expansion Arm F<br>NGM707 with pembrolizumab in SCCHN | Drug: NGM707 plus pembrolizumab<br>* Drug: NGM707 Preliminary recommended phase 2 dose (RP2D) of NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle. Drug: pembrolizumab Pembrolizumab will be administered intravenously (IV) every 3 weeks in a 21 day cycle.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients with Dose-limiting Toxicities | 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 28 days after the first dose of study treatment. | Baseline up to 28 Days | 
| Incidence of Adverse Events | Number of patients with adverse events (AEs) according to severity, seriousness, and relationship to study drug 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 with Clinically Significant Laboratory Abnormalities | Number of patients with clinically significant change from baseline in laboratory abnormalities as characterized by type, frequency, severity (graded by CTCAE version 5.0) and timing. | Baseline up to Approximately 24 Months | 
| Number of Patients in Expansion Cohorts with Objective Responses | Objective Response Rate is defined as the proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 | Baseline up to approximately 24 months | 
| Duration of Response for Patients in Expansion Cohorts | Duration of Response is defined as the time from the first documentation of objective response (CR or PR) that is subsequently confirmed per RECIST v1.1, to the time of the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. | Baseline up to approximately 24 months | 
| Progression-free Survival for Patients in Expansion Cohorts | Progression-free survival is defined as the time from start of study treatment to the date of first documentation of objective tumor progression on or following study therapy per RECIST v1.1, or to death due to any cause, whichever comes first. | Baseline up to approximately 24 months | 
| Overall Survival for Patients in Combination Dose Expansion Cohorts | Overall survival is defined as the date from start of the study treatment to the date of death due to any cause. | Up to approximately 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observed Plasma Concentration of NGM707 (Including 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 | 
| Area Under the Curve (AUC) of Plasma NGM707 | Area under the curve from time zero extrapolated to the last quantifiable dose of NGM707. Time zero extrapolated to the last quantifiable 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 | 
| Plasma Half-life (t1/2) of NGM707 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. 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 NGM707 | Incidence and titers of anti-drug antibodies (ADA) against NGM707. Will be measured on Day 1 of each cycle. | Baseline up to approximately 24 months |