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

A Phase 1/1b Dose Escalation/Expansion Study of NGM438 as Monotherapy and in Combination With Pembrolizumab in Advanced or Metastatic Solid Tumors

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

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Renal Cell Carcinoma; Cervical Cancer; Breast Cancer; Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Esophageal Cancer; Ovarian Cancer; Prostate Cancer; Non Small Cell Lung Cancer; Mesothelioma; Squamous Cell Carcinoma of Head and Neck; Cholangiocarcinoma; Bladder Urothelial Cancer; Endocervical Cancer
• Intervention / Treatment: Drug: NGM438; Drug: Pembrolizumab (KEYTRUDA ®)

• Study Type: Interventional
• Enrollment (Estimated): 71
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • SCRI Denver
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Grand Rapids, Michigan, United States, 49546
      • Start Midwest
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NGM438 Monotherapy Dose Escalation; Part 1a Single Agent Dose Escalation	Drug: NGM438; NGM438 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.
Experimental: NGM438 Combination Dose Finding with pembrolizumab ( KEYTRUDA ® ); Part 1b NGM438 plus pembrolizumab ( KEYTRUDA ® )	Drug: NGM438; NGM438 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.; Drug: Pembrolizumab (KEYTRUDA ®); Pembrolizumab (KEYTRUDA®) will be administered intravenously (IV) every 3 weeks in a 21 day cycle.
Experimental: Biopsy Cohort with NGM438 Monotherapy Followed by Combination Therapy with Pembrolizumab(KEYTRUDA ®); Part 1C NGM438 followed by NGM438 plus pembrolizumab ( KEYTRUDA ® )	Drug: NGM438; NGM438 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.; Drug: Pembrolizumab (KEYTRUDA ®); Pembrolizumab (KEYTRUDA®) will be administered intravenously (IV) every 3 weeks in a 21 day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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 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

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.
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.
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.
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.
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
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.

Collaborators and Investigators

• Sponsor: NGM Biopharmaceuticals, Inc
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2022
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: March 18, 2022
• First Submitted That Met QC Criteria: March 27, 2022
• First Posted (Actual): April 5, 2022

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Kidney Neoplasms; Adenoma; Carcinoma, Squamous Cell; Neoplasms, Mesothelial; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma; Squamous Cell Carcinoma of Head and Neck; Cholangiocarcinoma; Mesothelioma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 438-IO-101; KEYNOTE-E20 (Other Identifier: Merck Sharp & Dohme LLC); MK-3475-E20 (Other Identifier: Merck Sharp & Dohme LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No