Study of NGM707 As Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies

A Phase 1/2 Dose Escalation/Expansion Study of NGM707 As Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies

Study of NGM707 as Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Renal Cell Carcinoma; Cervical Cancer; Breast Cancer; Glioblastoma; Gastric Cancer; Colorectal Cancer; Esophageal Cancer; Ovarian Cancer; Non Small Cell Lung Cancer; Mesothelioma; Squamous Cell Carcinoma of Head and Neck; Cholangiocarcinoma; Pancreatic Ductal Adenocarcinoma; Endocervical Cancer
• Intervention / Treatment: Drug: NGM707; Drug: NGM707 plus pembrolizumab (KEYTRUDA®)

• Study Type: Interventional
• Enrollment (Estimated): 179
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • NGM Clinical Study Site
  • Seoul, Korea, Republic of, 05505
    • NGM Clinical Study Site
  • Seoul, Korea, Republic of, 06351
    • NGM Clinical Study Site
• Taiwan
  • New Taipei City, Taiwan, 235
    • NGM Clinical Study Site
  • Taichung, Taiwan, 404327
    • NGM Clinical Study Site
  • Tainan, Taiwan, 704
    • NGM Clinical Study Site
  • Taipei, Taiwan, 100225
    • NGM Clinical Study Site
• United States
  • California
    • Los Angeles, California, United States, 90033
      • NGM Clinical Study Site
    • Newport Beach, California, United States, 92663
      • NGM Clinical Study Site
    • Santa Monica', California, United States, 90404
      • NGM Clinical Study Site
    • Santa Rosa, California, United States, 94505
      • NGM Clinical Study Site
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • NGM Clinical Study Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • NGM Clinical Study Site
  • Florida
    • Sarasota, Florida, United States, 34232
      • NGM Clinical Study Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • NGM Clinical Study Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • NGM Clinical Study Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • NGM Clinical Study Site
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • NGM Clinical Study Site
  • New York
    • Albany, New York, United States, 12206
      • NGM Clinical Study Site
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • NGM Clinical Study Site
  • Texas
    • Dallas, Texas, United States, 75246
      • NGM Clinical Study Site
    • Dallas, Texas, United States, 78701
      • NGM Clinical Study Site
    • Houston, Texas, United States, 77030
      • NGM Clinical Study Site
    • San Antonio, Texas, United States, 78229
      • NGM Clinical Study Site
    • San Antonio, Texas, United States, 78240
      • NGM Clinical Study Site
  • Virginia
    • Blacksburg, Virginia, United States, 24060
      • NGM Clinical Study Site
  • Washington
    • Vancouver, Washington, United States, 98684
      • NGM Clinical Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 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, and for which the patient was eligible and willing to receive, or refused 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 ILT2 and/or ILT4 or targeting HLA-G.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NGM707 Monotherapy Dose Escalation; Part 1a Single Agent Dose Escalation	Drug: NGM707; Drug: NGM707 NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.
Experimental: NGM707 Combination Dose Finding with pembrolizumab (KEYTRUDA®); Part 1b NGM707 plus pembrolizumab (KEYTRUDA®)	Drug: NGM707 plus pembrolizumab (KEYTRUDA®); Drug: NGM707 NGM707 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: NGM707 Combination Dose Expansion Arm A; NGM707 with pembrolizumab (KEYTRUDA®) in Squamous NSCLC	Drug: NGM707 plus pembrolizumab (KEYTRUDA®); Drug: NGM707 NGM707 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: NGM707 Combination Dose Expansion Arm B; NGM707 with pembrolizumab (KEYTRUDA®) in Non-Squamous NSCLC	Drug: NGM707 plus pembrolizumab (KEYTRUDA®); Drug: NGM707 NGM707 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: NGM707 Combination Dose Expansion Arm C; NGM707 with pembrolizumab (KEYTRUDA®) in SCCHN	Drug: NGM707 plus pembrolizumab (KEYTRUDA®); Drug: NGM707 NGM707 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: NGM707 Monotherapy Dose Expansion Arm D; NGM707 in RCC	Drug: NGM707; Drug: NGM707 NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.
Experimental: NGM707 Monotherapy Dose Expansion Arm E; NGM707 in CRC	Drug: NGM707; Drug: NGM707 NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.
Experimental: NGM707 Monotherapy Dose Expansion Arm F; NGM707 in Ovarian	Drug: NGM707; Drug: NGM707 NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.

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 28 days after the first dose of study treatment.	Baseline up to 28 Days
Incidence of 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 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.	Baseline up to 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.	Baseline up to Approximately 24 Months
Number of Patients in Expansion 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) according to RECIST v1.1	Baseline up to approximately 24 months
Duration of Response for Patients in Expansion Cohorts	Duration of Response is defined as the time from the first documentation of objective response (CR or PR) that is subsequently confirmed per RECIST v1.1, to the time of the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.	Baseline up to approximately 24 months
Progression-free Survival for Patients in Expansion Cohorts	Progression-free survival is defined as the time from start of study treatment to the date of first documentation of objective tumor progression on or following study therapy per RECIST v1.1, or to death due to any cause, whichever comes first.	Baseline up to approximately 24 months
Overall Survival for Patients in Combination Dose Expansion Cohorts	Overall survival is defined as the date from start of the study treatment to the date of death due to any cause.	Up to approximately 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observed Plasma Concentration of NGM707 (Including 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.	Baseline up to approximately 24 months
Area Under the Curve (AUC) of Plasma NGM707	Area under the curve from time zero extrapolated to the last quantifiable dose of NGM707. Time zero extrapolated to the last quantifiable 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.	Baseline up to approximately 24 months
Plasma Half-life (t1/2) of NGM707	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. 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.	Baseline up to approximately 24 months
Anti-drug Antibodies (ADA) Against NGM707	Incidence and titers of anti-drug antibodies (ADA) against NGM707. Will be measured on Day 1 of each cycle.	Baseline up to approximately 24 months

Collaborators and Investigators

• Sponsor: NGM Biopharmaceuticals, Inc
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Chief Medical Officer, NGM Biopharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2021
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: May 20, 2021
• First Submitted That Met QC Criteria: June 2, 2021
• First Posted (Actual): June 4, 2021

Study Record Updates

• Last Update Posted (Actual): October 2, 2024
• Last Update Submitted That Met QC Criteria: September 30, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Adenoma; Carcinoma, Squamous Cell; Neoplasms, Mesothelial; Carcinoma; Glioblastoma; 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: 707-IO-101; KEYNOTE-D25 (Other Identifier: Merck Sharp & Dohme Corp); MK-3475-D25 (Other Identifier: Merck Sharp & Dohme Corp)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No