Breast Cancer, Cervical Cancer, Cholangiocarcinoma, Colorectal Cancer, Endocervical Cancer, Esophageal Cancer, Gastric Cancer, Glioblastoma, Melanoma, Mesothelioma, Non Small Cell Lung Cancer, Ovarian Cancer, Pancreatic Ductal Adenocarcinoma, Renal Cell Carcinoma, Squamous Cell Carcinoma of Head and Neck
Conditions
Brief summary
Study of NGM707 as Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies
Interventions
DRUGNGM707
Drug: NGM707 NGM707 is given intravenously (IV) every 3 weeks in a 21 day cycle. Multiple dose levels will be evaluated.
DRUGNGM707 plus pembrolizumab (KEYTRUDA®)
Drug: NGM707 NGM707 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
FACTORIAL
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. * Progressed or was intolerant to all available therapies known to confer clinical benefit appropriate for their tumor type, and for which the patient was eligible and willing to receive, or refused SOC treatments that are perceived to have marginal clinical benefit. * 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 ILT2 and/or ILT4 or targeting HLA-G.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival for Patients in Combination Dose Expansion Cohorts | Up to approximately 48 months | Overall survival is defined as the date from start of the study treatment to the date of death due to any cause. |
| Number of Patients with Clinically Significant Laboratory Abnormalities | Baseline up to Approximately 24 Months | 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. |
| Number of Patients in Expansion Cohorts 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) according to RECIST v1.1 |
| Duration of Response for Patients in Expansion Cohorts | Baseline up to approximately 24 months | Duration of Response is defined as the time from the first documentation of objective response (CR or PR) that is subsequently confirmed per RECIST v1.1, to the time of the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. |
| Progression-free Survival for Patients in Expansion Cohorts | Baseline up to approximately 24 months | Progression-free survival is defined as the time from start of study treatment to the date of first documentation of objective tumor progression on or following study therapy per RECIST v1.1, or to death due to any cause, whichever comes first. |
| Number of Patients with Dose-limiting Toxicities | Baseline up to 28 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 28 days after the first dose of study treatment. |
| Incidence of Adverse Events | Baseline up to Approximately 24 Months | Number of patients with adverse events (AEs) according to severity, seriousness, and relationship to study drug 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 Curve (AUC) of Plasma NGM707 | Baseline up to approximately 24 months | Area under the curve from time zero extrapolated to the last quantifiable dose of NGM707. Time zero extrapolated to the last quantifiable time point prior to the next dose. Will be measured on Day 1, 2, 4, 8 and 15 of Cycles 1 and 3, Day 1 of Cycle 2 and Day 1 of Cycle 4 and each cycle thereafter. |
| Plasma Half-life (t1/2) of NGM707 | Baseline up to approximately 24 months | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Will be measured on Day 1, 2, 4, 8 and 15 of Cycles 1 and 3, Day 1 of Cycle 2 and Day 1 of Cycle 4 and each cycle thereafter. |
| Anti-drug Antibodies (ADA) Against NGM707 | Baseline up to approximately 24 months | Incidence and titers of anti-drug antibodies (ADA) against NGM707. Will be measured on Day 1 of each cycle. |
| Observed Plasma Concentration of NGM707 (Including Cmax) | Baseline up to approximately 24 months | Will be measured on Day 1, 2, 4, 8 and 15 of Cycles 1 and 3, Day 1 of Cycle 2 and Day 1 of Cycle 4 and each cycle thereafter. |
Countries
South Korea, Taiwan, United States
Outcome results
None listed