Bladder Urothelial Cancer, Breast Cancer, Cervical Cancer, Cholangiocarcinoma, Colorectal Carcinoma, Endocervical Cancer, Esophageal Cancer, Gastric Cancer, Melanoma, Mesothelioma, Non-small Cell Lung Cancer, Ovarian Cancer, Pancreatic Cancer, Prostate Cancer, Renal Cell Carcinoma, Squamous Cell Carcinoma of Head and Neck
Conditions
Brief summary
Study of NGM831 as Monotherapy and in Combination with Pembrolizumab or Pembrolizumab and NGM438 in Advanced or Metastatic Solid Tumors
Interventions
DRUGNGM831
Drug: NGM831 NGM831 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.
DRUGNGM831 plus pembrolizumab (KEYTRUDA®)
Drug: NGM831 NGM831 is given intravenously (IV) every 3 weeks in a 21day cycle. Multiple dose levels will be evaluated. Drug: pembrolizumab (KEYTRUDA®) pembrolizumab (KEYTRUDA®) will be administered intravenously (IV) every 3 weeks in a 21day cycle.
DRUGNGM831 and NGM438 plus pembrolizumab (KEYTRUDA®)
Drug: NGM831 NGM831 is given intravenously (IV) every 3 weeks in a 21-day cycle. Multiple dose levels will be evaluated. Drug: NGM438 NGM438 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.
Sponsors
Merck Sharp & Dohme LLC
NGM Biopharmaceuticals, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically documented locally advanced or metastatic solid tumor malignancy. * 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 ILT3. * Prior treatment targeting LAIR1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients with Dose-limiting Toxicities | Baseline up to 21 Days | 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 21 days after the first dose of study treatment. |
| Incidence of Adverse Events | Baseline up to Approximately 24 months | Number of patients with treatment-emergent adverse events (AEs) 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration Time Curve of the dosing interval (AUC) of Serum NGM831 | Baseline up to approximately 9 weeks | AUC is defined as area under the concentration time curve of the dosing interval post drug administration. Will be calculated for Cycle 1 and Cycle 3. |
| Maximum Observed Serum Concentration (Cmax) of NGM438 | Baseline up to approximately 9 weeks | Cmax is defined as the observed maximum serum concentration post drug administration.Will be measured for Cycle 1 and Cycle 3. |
| Time to Maximum Observed Serum Concentration (Tmax) of NGM438. | Baseline up to approximately 9 weeks | Tmax is defined as the time to reach the observed maximum serum concentration (Cmax) post drug administration. Will be measured for Cycle 1 and Cycle 3. |
| Area Under the Concentration Time Curve of the dosing interval (AUC) of Serum NGM438 | Baseline up to approximately 9 weeks | AUC is defined as area under the concentration time curve of the dosing interval post drug administration. Will be calculated for Cycle 1 and Cycle 3. |
| Maximum Observed Serum Concentration (Cmax) of NGM831 | Baseline up to approximately 9 weeks | Cmax is defined as the observed maximum serum concentration post drug administration. Will be measured for Cycle 1 and Cycle 3. |
| Anti-drug Antibodies (ADA) Against NGM438 | Baseline up to approximately 24 months | Incidence and titers of anti-drug antibodies (ADA) against NGM438. Will be measured on Day 1 of each cycle. |
| Neutralizing antibodies (nAb) against NGM831 | Baseline up to approximately 24 months | Incidence and titers of neutralizing antibodies (nAb) against NGM831. Will be measured on Day 1 of each cycle. |
| Neutralizing antibodies (nAb) against NGM438 | Baseline up to approximately 24 months | Incidence and titers of neutralizing antibodies (nAb) against NGM438. Will be measured on Day 1 of each cycle. |
| Number of Patients with Objective Responses | Baseline up to approximately 24 months | Objective Response Rate is defined as the proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) divided by the total number of evaluable patients per RECIST v1.1. |
| Anti-drug Antibodies (ADA) Against NGM831 | Baseline up to approximately 24 months | Incidence and titers of anti-drug antibodies (ADA) against NGM831. Will be measured on Day 1 of each cycle. |
| Time to Maximum Observed Serum Concentration (Tmax) of NGM831 | Baseline up to approximately 9 weeks | Tmax is defined as the time to reach the observed maximum serum concentration (Cmax) post drug administration. Will be measured for Cycle 1 and Cycle 3. |
Countries
United States
Outcome results
None listed