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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04068896
• Other study ID #: 18-0402
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: October 16, 2019
• Est. completion date: January 2025

Study information

• Verified date: May 2023
• Source: NGM Biopharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 75
• Est. completion date: January 2025
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bladder Cancer
• Colorectal Cancer
• Esophageal Cancer
• Gastric Cancer
• Head Neck Squamous Cell Carcinoma
• Melanoma
• Metastatic Castration-resistant Prostate Cancer
• Non-small Cell Lung Cancer
• Ovarian Cancer
• Pancreatic Cancer
• Pancreatic Neoplasms
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Biological:
• NGM120
NGM120 Dose 1
• NGM120
NGM120 Dose 2
• NGM120
NGM120 Dose 3
• NGM120
NGM120 Dose 4
• NGM120
NGM120 Dose 5
• NGM120
NGM120 Dose 6

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
United States	NGM Clinical Study Site	Aurora	Colorado
United States	NGM Clinical Study Site	Baltimore	Maryland
United States	NGM Clinical Study Site	Charleston	South Carolina
United States	NGM Clinical Study Site	Charlotte	North Carolina
United States	NGM Clinical Study Site	Chicago	Illinois
United States	NGM Clinical Study Site	Cincinnati	Ohio
United States	NGM Clinical Study Site	Dallas	Texas
United States	NGM Clinical Study Site	Houston	Texas
United States	NGM Clinical Study Site	Los Angeles	California
United States	NGM Clinical Study Site	Los Angeles	California
United States	NGM Clinical Study Site	Miami	Florida
United States	NGM Clinical Study Site	Milwaukee	Wisconsin
United States	NGM Clinical Study Site	Myrtle Beach	South Carolina
United States	NGM Clinical Study Site	Nashville	Tennessee
United States	NGM Clinical Study Site	Omaha	Nebraska
United States	NGM Clinical Study Site	Philadelphia	Pennsylvania
United States	NGM Clinical Study Site	Sacramento	California
United States	NGM Clinical Study Site	San Diego	California
United States	NGM Clinical Study Site	Santa Monica	California
United States	NGM Clinical Study Site	Seattle	Washington
United States	NGM Clinical Study Site	Tucson	Arizona
United States	NGM Clinical Study Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
NGM Biopharmaceuticals, Inc

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 28 days after the first dose of study treatment.	12 weeks
Primary	Incidence of Adverse Events	Number of patients with adverse events (AEs) according to severity, seriousness, and relationship to study drug	12 weeks
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.	12 weeks
Secondary	Pharmacokinetics (PK) of NGM120	Pharmacokinetics (PK) of NGM120 by measuring serum concentration of NGM120 at specified timepoints	19 weeks
Secondary	Immunogenicity against NGM120	Immunogenicity against NGM120 by measuring percentage of subjects to develop antidrug antibodies and neutralizing antibodies	19 weeks
Secondary	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
Secondary	Body weight during therapy with NGM120	Body weight during therapy with NGM120 by measuring change in body weight (in lb).	19 weeks
Secondary	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