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

Study Overview
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Brief Summary
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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).

Official Title
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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

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

Intervention / Treatment
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* Biological: NGM120
* Biological: NGM120
* Biological: NGM120
* Biological: NGM120
* Biological: NGM120
* Biological: NGM120
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Part 1 and 2): Have histologically confirmed metastatic pancreatic adenocarcinoma. Recurrent unresectable pancreatic cancer is acceptable as long as the treatment is first-line. Have not received any approved chemotherapy, except in the adjuvant setting. Life expectancy of at least 12 weeks 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. 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): Metastatic, castrate resistance, histologically confirmed prostate cancer; continuous medical castration for ≥8 weeks prior to screening. Effective castration with serum testosterone levels <0.5 ng/mL (50 ng/dL; 1.7 nmol/L). Have serum GDF15 levels ≥1300 pg/mL. 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. Have had PSA doubling time of >3 months. Exclusion Criteria (All parts): 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. Subject has active infections or other serious underlying significant medical illness, abnormal and clinically significant laboratory findings or psychiatric illness/social situation. Subject is using a pacemaker, implantable cardiac defibrillator, neurostimulator, cochlear implants, cochlear implants, or other electronic medical equipment. Subject has documented immunodeficiency or organ transplant. Subject has an untreated central nervous system disease, leptomeningeal disease or cord compression. 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. Subject has a history or presence of documented inflammatory bowel disease. Subject is known to be positive for human immunodeficiency virus (HIV) infection.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NGM120 Dose 1<br>NGM120 Subcutaneous Injection | Biological: NGM120<br>* NGM120 Dose 1<br>|
| Experimental: NGM120 Dose 2<br>NGM120 Subcutaneous Injection | Biological: NGM120<br>* NGM120 Dose 2<br>|
| Experimental: NGM120 Dose 3<br>NGM120 Subcutaneous Injection | Biological: NGM120<br>* NGM120 Dose 3<br>|
| Experimental: NGM120 Dose 4<br>NGM120 Subcutaneous Injection | Biological: NGM120<br>* NGM120 Dose 4<br>|
| Experimental: NGM120 Dose 5<br>NGM120 Subcutaneous Injection | Biological: NGM120<br>* NGM120 Dose 5<br>|
| Experimental: NGM120 Dose 6<br>NGM120 Subcutaneous Injection | Biological: NGM120<br>* NGM120 Dose 6<br>|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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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 |