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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05311618
• Other study ID #: 438-IO-101
• Secondary ID: KEYNOTE-E20MK-34
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 11, 2022
• Est. completion date: June 2025

Study information

• Verified date: March 2024
• Source: NGM Biopharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 71
• Est. completion date: June 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bladder Urothelial Cancer
• Breast Cancer
• Carcinoma
• Carcinoma, Renal Cell
• Cervical Cancer
• Cholangiocarcinoma
• Colorectal Cancer
• Esophageal Cancer
• Gastric Cancer
• Melanoma
• Mesothelioma
• Non Small Cell Lung Cancer
• Ovarian Cancer
• Pancreatic Cancer
• Prostate Cancer
• Renal Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• NGM438
NGM438 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.
• Pembrolizumab (KEYTRUDA ®)
Pembrolizumab (KEYTRUDA®) will be administered intravenously (IV) every 3 weeks in a 21 day cycle.

Locations

Country	Name	City	State
United States	SCRI Denver	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	START Midwest	Grand Rapids	Michigan
United States	MD Anderson	Houston	Texas
United States	Yale Cancer Center	New Haven	Connecticut
United States	Mount Sinai Hospital	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
NGM Biopharmaceuticals, Inc	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline up to 21 Days
Primary	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.	Approximately 24 months
Primary	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.	Approximately 24 months
Primary	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
Primary	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
Primary	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	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	Approximately 24 months. Each Cycle is 21 days.
Secondary	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	Approximately 24 months. Each Cycle is 21 days.
Secondary	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	Approximately 24 months. Each Cycle is 21 days.
Secondary	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	Approximately 24 months. Each Cycle is 21 days.
Secondary	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	Approximately 24 months. Each Cycle is 21 days.
Secondary	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	Approximately 24 months. Each Cycle is 21 days.
Secondary	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.	Approximately 24 months. Each Cycle is 21 days.
Secondary	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	Approximately 24 months
Secondary	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.	Approximately 24 months. Each Cycle is 21 days.