Study of NGM120 in Subjects With Advanced Solid Tumors, Pancreatic Cancer, and Prostate Cancer Using Combination Therapy

A Phase 1/2 Dose-Finding Study Followed by Expansion Cohorts of NGM120, a GFRAL Antagonist Monoclonal Antibody Blocking GDF15 Signaling, in Subjects With Advanced Solid Tumors and Pancreatic Cancer Using Combination Therapy

Study of NGM120 in subjects with advanced solid tumors and and pancreatic cancer (Part 1 and 2) and metastatic castration resistant prostate cancer (Part 3).

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Esophageal Cancer; Ovarian Cancer; Prostate Cancer; Bladder Cancer; Non-small Cell Lung Cancer; Metastatic Castration-resistant Prostate Cancer; Head Neck Squamous Cell Carcinoma
• Intervention / Treatment: Other: Placebo; Biological: NGM120; Biological: NGM120; Biological: NGM120; Biological: NGM120; Biological: NGM120; Biological: NGM120

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: NGM Study Director; Phone Number: 650-243-5555; Email: ngm120@ngmbio.com

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • NGM Clinical Study Site
  • California
    • Los Angeles, California, United States, 90048
      • NGM Clinical Study Site
    • Los Angeles, California, United States, 90084
      • NGM Clinical Study Site
    • Sacramento, California, United States, 98517
      • NGM Clinical Study Site
    • San Diego, California, United States, 92123
      • NGM Clinical Study Site
    • Santa Monica, California, United States, 90404
      • NGM Clinical Study Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • NGM Clinical Study Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • NGM Clinical Study Site
  • Florida
    • Miami, Florida, United States, 33136
      • NGM Clinical Study Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • NGM Clinical Study Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • NGM Clinical Study Site
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • NGM Clinical Study Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • NGM Clinical Study Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • NGM Clinical Study Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • NGM Clinical Study Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • NGM Clinical Study Site
    • Myrtle Beach, South Carolina, United States, 29572
      • NGM Clinical Study Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • NGM Clinical Study Site
  • Texas
    • Dallas, Texas, United States, 75390
      • NGM Clinical Study Site
    • Houston, Texas, United States, 77030
      • NGM Clinical Study Site
  • Washington
    • Seattle, Washington, United States, 98101
      • NGM Clinical Study Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • NGM Clinical Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (Part 1 and 2):

1. Have histologically confirmed metastatic pancreatic adenocarcinoma. Recurrent unresectable pancreatic cancer is acceptable as long as the treatment is first-line.
2. Have not received any approved chemotherapy, except in the adjuvant setting.
3. Life expectancy of at least 12 weeks
4. Male subjects must agree to use contraception as per protocol during the treatment period and for at least 90 days after the last study treatment administration and refrain from donating sperm during this period.
5. Provision of an archival tumor sample (within 5 years). If an archival sample is unavailable, a fresh biopsy can be obtained during Screening. If archival tissue or biopsy sample is unavailable, the subject is ineligible.

Inclusion Criteria (Part 3 Prostate Cancer):

1. Metastatic, castrate resistance, histologically confirmed prostate cancer; continuous medical castration for ≥8 weeks prior to screening.
2. Effective castration with serum testosterone levels <0.5 ng/mL (50 ng/dL; 1.7 nmol/L).
3. Have serum GDF15 levels ≥1300 pg/mL.
4. Have experienced PSA progression under 1 or more lines of ADT in the absence or presence of radiographic and/or clinical progression, who decline or are not eligible to receive chemotherapy.
5. Have had PSA doubling time of >3 months.

Exclusion Criteria (All parts):

1. Subject was using immunosuppressive medications within 14 days before Screening with the exception of topical (intranasal, inhaled, and local injection), systemic (prednisone equivalent 10 mg/day or less), or as needed for hypersensitivity reactions such as computed tomography (CT) scan premedication.
2. Subject has active infections or other serious underlying significant medical illness, abnormal and clinically significant laboratory findings or psychiatric illness/social situation.
3. Subject is using a pacemaker, implantable cardiac defibrillator, neurostimulator, cochlear implants, cochlear implants, or other electronic medical equipment.
4. Subject has documented immunodeficiency or organ transplant.
5. Subject has an untreated central nervous system disease, leptomeningeal disease or cord compression.
6. Subject has a history, or presence, of significant cardiovascular diseases; including uncontrolled hypertension, clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months before randomization, congestive heart failure > New York Heart Association Class II, severe peripheral vascular disease, corrected QT (QTc) prolongation >470 msec, clinically significant pericardial effusion.
7. Subject has a history or presence of documented inflammatory bowel disease.
8. Subject is known to be positive for human immunodeficiency virus (HIV) infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo
Experimental: NGM120 Dose 1; NGM120 Subcutaneous Injection	Biological: NGM120; NGM120 Dose 1; Biological: NGM120; NGM120 Dose 2; Biological: NGM120; NGM120 Dose 3; Biological: NGM120; NGM120 Dose 4; Biological: NGM120; NGM120 Dose 5; Biological: NGM120; NGM120 Dose 6
Experimental: NGM120 Dose 2; NGM120 Subcutaneous Injection	Biological: NGM120; NGM120 Dose 1; Biological: NGM120; NGM120 Dose 2; Biological: NGM120; NGM120 Dose 3; Biological: NGM120; NGM120 Dose 4; Biological: NGM120; NGM120 Dose 5; Biological: NGM120; NGM120 Dose 6
Experimental: NGM120 Dose 3; NGM120 Subcutaneous Injection	Biological: NGM120; NGM120 Dose 1; Biological: NGM120; NGM120 Dose 2; Biological: NGM120; NGM120 Dose 3; Biological: NGM120; NGM120 Dose 4; Biological: NGM120; NGM120 Dose 5; Biological: NGM120; NGM120 Dose 6
Experimental: NGM120 Dose 4; NGM120 Subcutaneous Injection	Biological: NGM120; NGM120 Dose 1; Biological: NGM120; NGM120 Dose 2; Biological: NGM120; NGM120 Dose 3; Biological: NGM120; NGM120 Dose 4; Biological: NGM120; NGM120 Dose 5; Biological: NGM120; NGM120 Dose 6
Experimental: NGM120 Dose 5; NGM120 Subcutaneous Injection	Biological: NGM120; NGM120 Dose 1; Biological: NGM120; NGM120 Dose 2; Biological: NGM120; NGM120 Dose 3; Biological: NGM120; NGM120 Dose 4; Biological: NGM120; NGM120 Dose 5; Biological: NGM120; NGM120 Dose 6
Experimental: NGM120 Dose 6; NGM120 Subcutaneous Injection	Biological: NGM120; NGM120 Dose 1; Biological: NGM120; NGM120 Dose 2; Biological: NGM120; NGM120 Dose 3; Biological: NGM120; NGM120 Dose 4; Biological: NGM120; NGM120 Dose 5; Biological: NGM120; NGM120 Dose 6

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.	12 weeks
Incidence of Adverse Events	Number of patients with adverse events (AEs) according to severity, seriousness, and relationship to study drug	12 weeks
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.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) of NGM120	Pharmacokinetics (PK) of NGM120 by measuring serum concentration of NGM120 at specified timepoints	19 weeks
Immunogenicity against NGM120	Immunogenicity against NGM120 by measuring percentage of subjects to develop antidrug antibodies and neutralizing antibodies	19 weeks
Assessment of Antitumor and Anticachexia Activity Assessed using the RECIST Version 1.1 criteria	Assessment of Antitumor and Anticachexia Activity Assessed using the RECIST Version 1.1 criteria	19 weeks
Body weight during therapy with NGM120	Body weight during therapy with NGM120 by measuring change in body weight (in lb).	19 weeks
Skeletal muscle index during therapy with NGM120	Skeletal muscle index during therapy with NGM120 by measuring skeletal muscle mass and adiposity at level of L3 on serial CT scan.	19 weeks

Collaborators and Investigators

• Sponsor: NGM Biopharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2019
• Primary Completion (Anticipated): July 1, 2024
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: August 22, 2019
• First Submitted That Met QC Criteria: August 23, 2019
• First Posted (Actual): August 28, 2019

Study Record Updates

• Last Update Posted (Estimate): May 4, 2023
• Last Update Submitted That Met QC Criteria: May 2, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Genital Neoplasms, Male; Prostatic Diseases; Pancreatic Diseases; Prostatic Neoplasms; Pancreatic Neoplasms
• Other Study ID Numbers: 18-0402

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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