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Study of NGM438 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumors

Primary Purpose

Pancreatic Cancer, Breast Cancer, Gastric Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
NGM438
Pembrolizumab
Sponsored by
NGM Biopharmaceuticals, Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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 for which the patient was eligible and willing to receive.
  • 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 LAIR1

Sites / Locations

  • Yale Cancer CenterRecruiting
  • Henry Ford Health SystemRecruiting
  • START MidwestRecruiting
  • Mount Sinai HospitalRecruiting
  • MD AndersonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

NGM438 Monotherapy Dose Escalation

NGM438 Combination Dose Finding with Pembrolizumab

Biopsy Cohort with NGM438 Monotherapy Lead-in Followed by Combination Therapy with Pembrolizumab

Arm Description

Part 1a Single Agent Dose Escalation

Part 1b NGM438 plus pembrolizumab

Part 1C NGM438 followed by NGM438 plus pembrolizumab

Outcomes

Primary Outcome Measures

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 21 days after the first dose of study treatment.
Number of Patients with 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 patient, 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
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.
Changes in potential pharmacodynamic biomarker CD163 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in CD163
Changes in potential pharmacodynamic biomarker MMP9 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in MMP9
Changes in potential pharmacodynamic biomarker CD8 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in CD8

Secondary Outcome Measures

Maximum Observed Serum Concentration (Cmax) of NGM438
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 Cycles 4-6 and every third cycle thereafter
Area Under the Curve (AUC) of Serum NGM438
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 Cycles 4-6 and every third cycle thereafter
Time to Maximum (Tmax) Observed Serum Concentration of NGM438
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 Cycles 4-6 and every third cycle thereafter
Half-life (t1/2) of NGM438 in Serum
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 Cycles 4-6 and every third cycle thereafter
Systemic Clearance (CL) of NGM438
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 Cycles 4-6 and every third cycle thereafter
Volume of Distribution (Vss) of NGM438 at Steady State
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 Cycles 4-6 and every third cycle thereafter
Anti-drug Antibodies (ADA) Against NGM438
Incidence and titers of anti-drug antibodies (ADA) against NGM438. Will be measured on Day 1 of each cycle through Cycle 6 and every third cycle thereafter.
Number of Patients in Dose Escalation and Dose Finding 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) divided by the total number of evaluable patients per RECIST v1.1
Trough Concentrations of NGM438 in Patients in the Biopsy Cohort
Trough Concentration refers to the serum concentration of NGM438 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.

Full Information

First Posted
March 18, 2022
Last Updated
October 6, 2022
Sponsor
NGM Biopharmaceuticals, Inc
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05311618
Brief Title
Study of NGM438 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumors
Official Title
A Phase 1/1b Dose Escalation/Expansion Study of NGM438 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 11, 2022 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NGM Biopharmaceuticals, Inc
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Study of NGM438 as Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumors

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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 Cancer, Esophageal Cancer, Ovarian Cancer, Renal Cell Carcinoma, Prostate Cancer, Melanoma, Mesothelioma, Cholangiocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
71 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
NGM438 Monotherapy Dose Escalation
Arm Type
Experimental
Arm Description
Part 1a Single Agent Dose Escalation
Arm Title
NGM438 Combination Dose Finding with Pembrolizumab
Arm Type
Experimental
Arm Description
Part 1b NGM438 plus pembrolizumab
Arm Title
Biopsy Cohort with NGM438 Monotherapy Lead-in Followed by Combination Therapy with Pembrolizumab
Arm Type
Experimental
Arm Description
Part 1C NGM438 followed by NGM438 plus pembrolizumab
Intervention Type
Drug
Intervention Name(s)
NGM438
Intervention Description
NGM438 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
Pembrolizumab will be administered intravenously (IV) every 3 weeks in a 21 day cycle.
Primary Outcome Measure Information:
Title
Number of Patients with Dose-limiting Toxicities
Description
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.
Time Frame
Baseline up to 21 Days
Title
Number of Patients with Adverse Events
Description
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 patient, 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.
Time Frame
Approximately 24 months
Title
Number of Patients with Clinically Significant Laboratory Abnormalities
Description
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.
Time Frame
Approximately 24 months
Title
Changes in potential pharmacodynamic biomarker CD163 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in CD163
Time Frame
Baseline up to 15 days
Title
Changes in potential pharmacodynamic biomarker MMP9 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in MMP9
Time Frame
Baseline up to 15 days
Title
Changes in potential pharmacodynamic biomarker CD8 in paired tumor tissue in Patients in the Biopsy Cohort Summary of baseline, post baseline and changes from baseline in CD8
Time Frame
Baseline up to 15 days
Secondary Outcome Measure Information:
Title
Maximum Observed Serum Concentration (Cmax) of NGM438
Description
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 Cycles 4-6 and every third cycle thereafter
Time Frame
Approximately 24 months. Each Cycle is 21 days.
Title
Area Under the Curve (AUC) of Serum NGM438
Description
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 Cycles 4-6 and every third cycle thereafter
Time Frame
Approximately 24 months. Each Cycle is 21 days.
Title
Time to Maximum (Tmax) Observed Serum Concentration of NGM438
Description
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 Cycles 4-6 and every third cycle thereafter
Time Frame
Approximately 24 months. Each Cycle is 21 days.
Title
Half-life (t1/2) of NGM438 in Serum
Description
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 Cycles 4-6 and every third cycle thereafter
Time Frame
Approximately 24 months. Each Cycle is 21 days.
Title
Systemic Clearance (CL) of NGM438
Description
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 Cycles 4-6 and every third cycle thereafter
Time Frame
Approximately 24 months. Each Cycle is 21 days.
Title
Volume of Distribution (Vss) of NGM438 at Steady State
Description
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 Cycles 4-6 and every third cycle thereafter
Time Frame
Approximately 24 months. Each Cycle is 21 days.
Title
Anti-drug Antibodies (ADA) Against NGM438
Description
Incidence and titers of anti-drug antibodies (ADA) against NGM438. Will be measured on Day 1 of each cycle through Cycle 6 and every third cycle thereafter.
Time Frame
Approximately 24 months. Each Cycle is 21 days.
Title
Number of Patients in Dose Escalation and Dose Finding Cohorts with Objective Responses
Description
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
Time Frame
Approximately 24 months
Title
Trough Concentrations of NGM438 in Patients in the Biopsy Cohort
Description
Trough Concentration refers to the serum concentration of NGM438 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.
Time Frame
Approximately 24 months. Each Cycle is 21 days.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 for which the patient was eligible and willing to receive. 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 LAIR1
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
NGM Medical Director
Phone
(650) 243-5555
Email
NGM438@ngmbio.com
Facility Information:
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Individual Site Status
Recruiting
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Individual Site Status
Recruiting
Facility Name
START Midwest
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49546
Country
United States
Individual Site Status
Recruiting
Facility Name
Mount Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Name
MD Anderson
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

Study of NGM438 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumors

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