A Phase 1/2 Dose Escalation/Expansion Study of NGM707 As Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 179
- Locations
- 1
- Primary Endpoint
- Number of Patients with Dose-limiting Toxicities
Study Overview
Brief Summary
Study of NGM707 as Monotherapy and in Combination with Pembrolizumab in Advanced or Metastatic Solid Tumor Malignancies
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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
- •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.
Arms & Interventions
NGM707 Monotherapy Dose Escalation
Part 1a Single Agent Dose Escalation
Intervention: NGM707 (Drug)
NGM707 Combination Dose Finding with pembrolizumab (KEYTRUDA®)
Part 1b NGM707 plus pembrolizumab (KEYTRUDA®)
Intervention: NGM707 plus pembrolizumab (KEYTRUDA®) (Drug)
NGM707 Combination Dose Expansion Arm A
NGM707 with pembrolizumab (KEYTRUDA®) in Squamous NSCLC
Intervention: NGM707 plus pembrolizumab (KEYTRUDA®) (Drug)
NGM707 Combination Dose Expansion Arm B
NGM707 with pembrolizumab (KEYTRUDA®) in Non-Squamous NSCLC
Intervention: NGM707 plus pembrolizumab (KEYTRUDA®) (Drug)
NGM707 Combination Dose Expansion Arm C
NGM707 with pembrolizumab (KEYTRUDA®) in SCCHN
Intervention: NGM707 plus pembrolizumab (KEYTRUDA®) (Drug)
NGM707 Monotherapy Dose Expansion Arm D
NGM707 in RCC
Intervention: NGM707 (Drug)
NGM707 Monotherapy Dose Expansion Arm E
NGM707 in CRC
Intervention: NGM707 (Drug)
NGM707 Monotherapy Dose Expansion Arm F
NGM707 in Ovarian
Intervention: NGM707 (Drug)
Outcomes
Primary Outcomes
Number of Patients with Dose-limiting Toxicities
Time Frame: 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.
Progression-free Survival for Patients in Expansion Cohorts
Time Frame: 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.
Duration of Response for Patients in Expansion Cohorts
Time Frame: 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.
Incidence of Adverse Events
Time Frame: 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.
Number of Patients with Clinically Significant Laboratory Abnormalities
Time Frame: 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
Time Frame: 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
Overall Survival for Patients in Combination Dose Expansion Cohorts
Time Frame: 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.
Secondary Outcomes
- Observed Plasma Concentration of NGM707 (Including Cmax)(Baseline up to approximately 24 months)
- Area Under the Curve (AUC) of Plasma NGM707(Baseline up to approximately 24 months)
- Plasma Half-life (t1/2) of NGM707(Baseline up to approximately 24 months)
- Anti-drug Antibodies (ADA) Against NGM707(Baseline up to approximately 24 months)