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

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Primary Purpose

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

NGM831

NGM831 plus pembrolizumab

NGM831

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, 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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

NGM831 Monotherapy Dose Escalation

NGM831 Combination Dose Finding with Pembrolizumab

NGM831 Monotherapy Dose Expansion

NGM831 Combination Dose Expansion Arm A

NGM831 Combination Dose Expansion Arm B

NGM831 Combination Dose Expansion Arm C

Arm Description

Part 1a Single Agent Dose Escalation

Part 1b NGM831 plus pembrolizumab

Part 2a Single Agent Dose Expansion

NGM831 plus pembrolizumab

Outcomes

Primary Outcome Measures

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.

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.

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

Secondary Outcome Measures

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

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.

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.

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.

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.

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.

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.

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.

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

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.

Full Information

NCT ID

NCT05215574

First Posted

January 19, 2022

Last Updated

April 26, 2023

Sponsor

NGM Biopharmaceuticals, Inc

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT05215574

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 31, 2022 (Actual)

Primary Completion Date

February 2024 (Anticipated)

Study Completion Date

December 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 NGM831 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 Carcinoma, 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

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

79 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

NGM831 Monotherapy Dose Escalation

Arm Type

Experimental

Arm Description

Part 1a Single Agent Dose Escalation

Arm Title

NGM831 Combination Dose Finding with Pembrolizumab

Arm Type

Experimental

Arm Description

Part 1b NGM831 plus pembrolizumab

Arm Title

NGM831 Monotherapy Dose Expansion

Arm Type

Experimental

Arm Description

Part 2a Single Agent Dose Expansion

Arm Title

NGM831 Combination Dose Expansion Arm A

Arm Type

Experimental

Arm Description

NGM831 plus pembrolizumab

Arm Title

NGM831 Combination Dose Expansion Arm B

Arm Type

Experimental

Arm Description

NGM831 plus pembrolizumab

Arm Title

NGM831 Combination Dose Expansion Arm C

Arm Type

Experimental

Arm Description

NGM831 plus pembrolizumab

Intervention Type

Drug

Intervention Name(s)

NGM831

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

NGM831 plus pembrolizumab

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

NGM831

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Patients with Dose-limiting Toxicities (Part 1)

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

Incidence of Adverse Events (Part 1 and Part 2)

Description

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.

Time Frame

Baseline up to Approximately 24 months

Title

Number of Patients in Expansion Cohort with Objective Responses (Part 2)

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

Baseline up to Approximately 24 months

Secondary Outcome Measure Information:

Title

Maximum Observed Serum Concentration (Cmax) of NGM831 (Part 1)

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 Cycle 4 and each cycle thereafter

Time Frame