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

Sponsor

NGM Biopharmaceuticals, Inc (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05215574

Collaborator

Merck Sharp & Dohme LLC (Industry)

Enrollment

Locations

Arms

32.1

Anticipated Duration (Months)

15.8

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
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	Drug: NGM831 Drug: NGM831 plus pembrolizumab Drug: NGM831	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

79 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 31, 2022

Anticipated Primary Completion Date :

Feb 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: NGM831 Monotherapy Dose Escalation

Part 1a Single Agent Dose Escalation

Drug: NGM831

Drug: NGM831 NGM831 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.

Experimental: NGM831 Combination Dose Finding with Pembrolizumab

Part 1b NGM831 plus pembrolizumab

Drug: NGM831 plus pembrolizumab

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.

Experimental: NGM831 Monotherapy Dose Expansion

Part 2a Single Agent Dose Expansion

Drug: NGM831

Drug: NGM831 Preliminary recommended phase 2 dose (RP2D) of NGM831 is given intravenously (IV) every 3 weeks in a 21 day cycle.

Outcome Measures

Primary Outcome Measures

Number of Patients with Dose-limiting Toxicities [Baseline up to 21 Days]
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.
Incidence of Adverse Events [Baseline up to Approximately 24 months]
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.
Number of Patients with Clinically Significant Laboratory Abnormalities [Baseline up to Approximately 24 months]
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.

Secondary Outcome Measures

Maximum Observed Serum Concentration (Cmax) of NGM831 [Baseline up to approximately 24 months]
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
Area Under the Curve (AUC) of Serum NGM831 [Baseline up to approximately 24 months]
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.
Time to Maximum (Tmax) Observed Serum Concentration of NGM831 [Baseline up to approximately 24 months]
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.
Half-life (t1/2) of NGM831 in Serum [Baseline up to approximately 24 months]
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.
Systemic Clearance (CL) of NGM831 [Baseline up to approximately 24 months]
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.
Volume of Distribution (Vss) of NGM831 at Steady State [Baseline up to approximately 24 months]
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.
Anti-drug Antibodies (ADA) Against NGM831 [Baseline up to approximately 24 months]
Incidence and titers of anti-drug antibodies (ADA) against NGM831. Will be measured on Day 1 of each cycle.
Number of Patients in Expansion Cohort with Objective Responses [Baseline up to approximately 24 months]
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
Trough Concentrations of NGM831 [Baseline up to approximately 24 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 standard-of-care (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 ILT3.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner MD Anderson Medical Center	Gilbert	Arizona	United States	85234
2	The Angeles Clinic	Los Angeles	California	United States	90025
3	START Midwest	Grand Rapids	Michigan	United States	49546
4	Next Oncology	Austin	Texas	United States	78758
5	The University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030