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, Prostate Cancer
Conditions
Brief summary
Study of NGM120 in subjects with advanced solid tumors and pancreatic cancer (Part 1 and 2) and metastatic castration resistant prostate cancer (Part 3).
Detailed description
The aim of the study is to evaluate the safety and tolerability of NGM120 monotherapy in subjects with select advanced solid tumors (Part 1), NGM120 in combination with gemcitabine and Abraxane for the management of metastatic pancreatic cancer (Part 2), and NGM120 in metastatic castration-resistant prostate cancer (mCRPC) patients who have progressed under 1 or more lines of ADT (Part 3), for up to 24 months of treatment.
Interventions
BIOLOGICALNGM120 30mg
NGM120 30mg Subcutaneous Injection
BIOLOGICALNGM120 100mg
NGM120 100mg Subcutaneous Injection
BIOLOGICALNGM120 30mg with Gemcitabine and Abraxane
NGM120 30mg Subcutaneous Injection together with gemcitabine (1000 mg/m2 weekly for first 3 weeks of the 4-week cycle) and Abraxane (125 mg/m2 weekly for first 3 weeks of the 4-week cycle).
BIOLOGICALNGM120 100mg with Gemcitabine and Abraxane
NGM120 100 mg Subcutaneous Injection together with gemcitabine (1000 mg/m2 weekly for first 3 weeks of the 4-week cycle) and Abraxane (125 mg/m2 weekly for first 3 weeks of the 4-week cycle).
BIOLOGICALNGM120 100mg Q3W
NGM120 100mg Subcutaneous Injection every 3 weeks
OTHERPlacebo
Placebo
Sponsors
NGM Biopharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Determine the Safety and Tolerability of NGM120 in Subjects | From enrollment to end of treatment up to 24 months | Number of Participants with NGM120/Placebo-Related Treatment Emergent Adverse Events |
| To Determine the Safety and Tolerability of NGM120 | From enrollment to end of treatment up to 24 months | Discontinuation of investigational product due to toxicity |
Countries
United States
Participant flow
Recruitment details
89 patients were enrolled (signed consent), however only 87 patients received at least 1 dose of study treatment. The participant flow contains information from these 87 treated patients, that are also considered the Safety Analysis set for CSR and study results
Participants by arm
| Arm | Count |
|---|---|
| Part 1 NGM120 30mg NGM120 30mg Subcutaneous Injection | 10 |
| Part 1 NGM120 100mg NGM120 100 mg Subcutaneous Injection | 10 |
| Part 2 NGM120 30mg NGM120 30mg Subcutaneous Injection together with gemcitabine (1000 mg/m2 weekly for first 3 weeks of the 4-week cycle) and Abraxane (125 mg/m2 weekly for first 3 weeks of the 4-week cycle). | 10 |
| Part 2 NGM120 100mg NGM120 100 mg Subcutaneous Injection together with gemcitabine (1000 mg/m2 weekly for first 3 weeks of the 4-week cycle) and Abraxane (125 mg/m2 weekly for first 3 weeks of the 4-week cycle). | 31 |
| Part 2 Placebo Placebo Subcutaneous Injection together with gemcitabine (1000 mg/m2 weekly for first 3 weeks of the 4-week cycle) and Abraxane (125 mg/m2 weekly for first 3 weeks of the 4-week cycle) | 20 |
| Part 3 NGM120 100mg NGM120 100 mg Subcutaneous Injection | 6 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Death | 3 | 1 | 3 | 19 | 17 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | progressive disease | 3 | 5 | 3 | 2 | 1 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Study terminated by sponsor | 0 | 0 | 1 | 2 | 1 | 4 |
| Overall Study | Symptomatic deterioration | 2 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 0 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 2 NGM120 30mg | Part 2 NGM120 100mg | Part 1 NGM120 30mg | Part 2 Placebo | Part 3 NGM120 100mg | Part 1 NGM120 100mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 20 Participants | 3 Participants | 16 Participants | 5 Participants | 8 Participants | 60 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 11 Participants | 7 Participants | 4 Participants | 1 Participants | 2 Participants | 27 Participants |
| Age, Continuous | 67.7 years STANDARD_DEVIATION 8.27 | 67.0 years STANDARD_DEVIATION 9.06 | 58.8 years STANDARD_DEVIATION 9.08 | 69.9 years STANDARD_DEVIATION 8.1 | 69.0 years STANDARD_DEVIATION 11.92 | 65.6 years STANDARD_DEVIATION 12.21 | 67.2 years STANDARD_DEVIATION 8.78 |
| BMI | 26.53 kg/m2 STANDARD_DEVIATION 9.694 | 25.72 kg/m2 STANDARD_DEVIATION 5.119 | 24.93 kg/m2 STANDARD_DEVIATION 5.759 | 25.04 kg/m2 STANDARD_DEVIATION 5.113 | 31.20 kg/m2 STANDARD_DEVIATION 5.852 | 26.46 kg/m2 STANDARD_DEVIATION 4.636 | 26.03 kg/m2 STANDARD_DEVIATION 5.89 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 30 Participants | 8 Participants | 15 Participants | 4 Participants | 9 Participants | 73 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 4 Participants | 1 Participants | 0 Participants | 7 Participants |
| Metastatic Disease No | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants |
| Metastatic Disease Yes | 10 Participants | 29 Participants | 9 Participants | 19 Participants | 6 Participants | 10 Participants | 83 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 7 Participants | 1 Participants | 6 Participants | 0 Participants | 0 Participants | 19 Participants |
| Race (NIH/OMB) White | 4 Participants | 17 Participants | 8 Participants | 11 Participants | 5 Participants | 8 Participants | 53 Participants |
| Sex: Female, Male Female | 8 Participants | 13 Participants | 4 Participants | 11 Participants | 0 Participants | 1 Participants | 37 Participants |
| Sex: Female, Male Male | 2 Participants | 18 Participants | 6 Participants | 9 Participants | 6 Participants | 9 Participants | 50 Participants |
| Sites of Metastases Bone | 1 count of metastatic sites | 1 count of metastatic sites | 3 count of metastatic sites | 0 count of metastatic sites | 5 count of metastatic sites | 6 count of metastatic sites | 16 count of metastatic sites |
| Sites of Metastases Liver | 5 count of metastatic sites | 17 count of metastatic sites | 5 count of metastatic sites | 16 count of metastatic sites | 0 count of metastatic sites | 4 count of metastatic sites | 47 count of metastatic sites |
| Sites of Metastases Lung | 4 count of metastatic sites | 10 count of metastatic sites | 2 count of metastatic sites | 5 count of metastatic sites | 1 count of metastatic sites | 4 count of metastatic sites | 26 count of metastatic sites |
| Sites of Metastases Other | 1 count of metastatic sites | 5 count of metastatic sites | 2 count of metastatic sites | 3 count of metastatic sites | 2 count of metastatic sites | 2 count of metastatic sites | 15 count of metastatic sites |
| Sites of Metastases Peritoneum | 2 count of metastatic sites | 2 count of metastatic sites | 2 count of metastatic sites | 0 count of metastatic sites | 0 count of metastatic sites | 0 count of metastatic sites | 6 count of metastatic sites |
| Time from Initial cancer diagnosis | 6.328 Months STANDARD_DEVIATION 12.919 | 4.769 Months STANDARD_DEVIATION 7.4036 | 40.775 Months STANDARD_DEVIATION 21.0265 | 4.350 Months STANDARD_DEVIATION 6.1938 | 140.167 Months STANDARD_DEVIATION 69.491 | 61.841 Months STANDARD_DEVIATION 67.6111 | 24.86 Months STANDARD_DEVIATION 47.45 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 10 | 1 / 10 | 3 / 10 | 19 / 31 | 17 / 20 | 0 / 6 |
| other Total, other adverse events | 10 / 10 | 10 / 10 | 10 / 10 | 31 / 31 | 20 / 20 | 6 / 6 |
| serious Total, serious adverse events | 5 / 10 | 3 / 10 | 5 / 10 | 26 / 31 | 10 / 20 | 1 / 6 |
Outcome results
Primary
To Determine the Safety and Tolerability of NGM120
Discontinuation of investigational product due to toxicity
Time frame: From enrollment to end of treatment up to 24 months
Population: Safety analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 NGM120 30mg | To Determine the Safety and Tolerability of NGM120 | 2 Participants |
| Part 1 NGM120 100mg | To Determine the Safety and Tolerability of NGM120 | 0 Participants |
| Part 2 NGM120 30mg | To Determine the Safety and Tolerability of NGM120 | 2 Participants |
| Part 2 NGM120 100mg | To Determine the Safety and Tolerability of NGM120 | 8 Participants |
| Part 2 Placebo | To Determine the Safety and Tolerability of NGM120 | 3 Participants |
| Part 3 NGM120 100mg | To Determine the Safety and Tolerability of NGM120 | 0 Participants |
Primary
To Determine the Safety and Tolerability of NGM120
Local injection-site symptom assessment as evidenced by incidence of injection-site reactions
Time frame: From enrollment to end of treatment up to 24 months
Population: Safety analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 NGM120 30mg | To Determine the Safety and Tolerability of NGM120 | 0 Participants |
| Part 1 NGM120 100mg | To Determine the Safety and Tolerability of NGM120 | 1 Participants |
| Part 2 NGM120 30mg | To Determine the Safety and Tolerability of NGM120 | 0 Participants |
| Part 2 NGM120 100mg | To Determine the Safety and Tolerability of NGM120 | 4 Participants |
| Part 2 Placebo | To Determine the Safety and Tolerability of NGM120 | 0 Participants |
| Part 3 NGM120 100mg | To Determine the Safety and Tolerability of NGM120 | 0 Participants |
Primary
To Determine the Safety and Tolerability of NGM120 in Subjects
Number of Participants with NGM120/Placebo-Related Treatment Emergent Adverse Events
Time frame: From enrollment to end of treatment up to 24 months
Population: Safety analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 NGM120 30mg | To Determine the Safety and Tolerability of NGM120 in Subjects | 1 Participants |
| Part 1 NGM120 100mg | To Determine the Safety and Tolerability of NGM120 in Subjects | 6 Participants |
| Part 2 NGM120 30mg | To Determine the Safety and Tolerability of NGM120 in Subjects | 6 Participants |
| Part 2 NGM120 100mg | To Determine the Safety and Tolerability of NGM120 in Subjects | 17 Participants |
| Part 2 Placebo | To Determine the Safety and Tolerability of NGM120 in Subjects | 12 Participants |
| Part 3 NGM120 100mg | To Determine the Safety and Tolerability of NGM120 in Subjects | 2 Participants |