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

Phase 1

Active, not recruiting

• Conditions: Bladder Urothelial Cancer; Prostate Cancer; Melanoma; Endocervical Cancer; Squamous Cell Carcinoma of Head and Neck; Ovarian Cancer; Pancreatic Cancer; Gastric Cancer; Cervical Cancer; Renal Cell Carcinoma
• Interventions: Drug: NGM438; Drug: Pembrolizumab (KEYTRUDA ®)

• Registration Number: NCT05311618
• Lead Sponsor: NGM Biopharmaceuticals, Inc

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-03-18
• Study First Submitted QC: 2022-03-27
• Study First Posted: 2022-04-05
• Study Start: 2022-05-11
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-28
• Last Update Posted: 2024-04-01
• Primary Completion: 2025-04
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 71

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
NGM438 Combination Dose Finding with pembrolizumab ( KEYTRUDA ® )	Pembrolizumab (KEYTRUDA ®)	Part 1b NGM438 plus pembrolizumab ( KEYTRUDA ® )
Biopsy Cohort with NGM438 Monotherapy Followed by Combination Therapy with Pembrolizumab(KEYTRUDA ®)	Pembrolizumab (KEYTRUDA ®)	Part 1C NGM438 followed by NGM438 plus pembrolizumab ( KEYTRUDA ® )
NGM438 Monotherapy Dose Escalation	NGM438	Part 1a Single Agent Dose Escalation
NGM438 Combination Dose Finding with pembrolizumab ( KEYTRUDA ® )	NGM438	Part 1b NGM438 plus pembrolizumab ( KEYTRUDA ® )
Biopsy Cohort with NGM438 Monotherapy Followed by Combination Therapy with Pembrolizumab(KEYTRUDA ®)	NGM438	Part 1C NGM438 followed by NGM438 plus pembrolizumab ( KEYTRUDA ® )

Primary Outcome Measures

Name	Time	Method
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	Baseline up to 15 days
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	Baseline up to 15 days
Number of Patients with Adverse Events	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 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 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.
Number of Patients with Clinically Significant Laboratory Abnormalities	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.
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	Baseline up to 15 days

Secondary Outcome Measures

Name	Time	Method
Systemic Clearance (CL) of NGM438	Approximately 24 months. Each Cycle is 21 days.	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	Approximately 24 months. Each Cycle is 21 days.	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	Approximately 24 months. Each Cycle is 21 days.	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.
Trough Concentrations of NGM438 in Patients in the Biopsy Cohort	Approximately 24 months. Each Cycle is 21 days.	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.
Maximum Observed Serum Concentration (Cmax) of NGM438	Approximately 24 months. Each Cycle is 21 days.	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 to Maximum (Tmax) Observed Serum Concentration of NGM438	Approximately 24 months. Each Cycle is 21 days.	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
Area Under the Curve (AUC) of Serum NGM438	Approximately 24 months. Each Cycle is 21 days.	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
Half-life (t1/2) of NGM438 in Serum	Approximately 24 months. Each Cycle is 21 days.	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
Number of Patients in Dose Escalation and Dose Finding Cohorts with Objective Responses	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

Trial Locations

Locations (6)

SCRI Denver; 🇺🇸 Denver, Colorado, United States

MD Anderson; 🇺🇸 Houston, Texas, United States

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

START Midwest; 🇺🇸 Grand Rapids, Michigan, United States

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

Mount Sinai Hospital; 🇺🇸 New York, New York, United States