This is an open-label, non-randomized, Phase 1b/2 study to determine the safety and tolerability of NC410 when combined with a standard dose of pembrolizumab. This study will also assess the clinical benefit of combination therapy in participants with advanced unresectable and/or metastatic ICI refractory solid tumors OR ICI naïve MSS/MSI-low solid tumors
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
97
NC410 will be given intravenously (IV) every 2 weeks
Pembrolizumab 400mg will be given IV every 6 weeks.
Arizona Oncology Associates
Tucson, Arizona, United States
Rocky Mountain Cancer Centers
Aurora, Colorado, United States
St. Elizabeth Edgewood Hospital
Edgewood, Kentucky, United States
Ochsner Cancer Institute
New Orleans, Louisiana, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Hackensack Meridian Health University Medical Center- John Theurer Cancer Center
Hackensack, New Jersey, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, United States
NYU Langone Health
New York, New York, United States
University of Cincinnati Cancer Center
Cincinnati, Ohio, United States
UT Southwestern Medical Center
Dallas, Texas, United States
...and 7 more locations
Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0
Number of Participants With Treatment-emergent Adverse Events
Time frame: From enrollment through up to 90 days after end of treatment, an average of 1 year
Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
To assess antitumor activity/efficacy by evaluating objective response rate (ORR), defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame: until disease progression, up to 24 months
Duration of Response Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
To assess antitumor activity/efficacy by evaluating duration of response (DoR), defined as the time from the first documented complete response or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 to the first documented progressive disease or death due to any cause, whichever occurs first. Subjects who are alive and progression free as of the analysis cut-off date, who discontinued the treatment or switched to a new treatment will be censored at their last evaluable tumor response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: CompleteResponse (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions
Time frame: until disease progression or death, up to 24 months
Disease Control Rate Per RECIST v1.1
To assess antitumor activity/efficacy by evaluating disease control rate (DCR), defined as the proportion of participants in whom a documented complete response, partial response, or stable disease is observed as the best overall response (lasting 24weeks or longer) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame: until disease progression, up to 24 months
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
To evaluate progression-free survival (PFS), defined as time (in months) from starting study treatment to the first documented progressive disease or death due to any cause, whichever occurs first. Progressive disease will include both 'Progressive Disease' and 'Clinical Signs and Symptoms Consistent with Progressive Disease' from the RECIST CRFs. For participants who are alive and progression free at the time of discontinuation from study, data cutoff for analysis, or use of other anticancer drug, PFS will be censored at the last tumor assessment date. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: until disease progression, up to 24 months
Overall Survival (OS)
Overall Survival, estimated using Kaplan-Meier, is defined as time in months from start of study treatment to death due to any cause. Subjects who were alive at the time of discontinuation from study or data cutoff for analysis were censored at their last known alive (LKA) date.
Time frame: From start of study treatment until death due to any cause or censoring at the last known alive date, assessed up to 24 months.
Maximum Serum Concentration (Cmax) of NC410
Maximum observed NC410 serum concentration at Cycle 1. Note participants enrolled at 200mg dose level were dosed with 100mg of NC410 at Cycle 1 Day 1.
Time frame: PK samples collected pre-dose, 30 minutes post-NC410 infusion (end of infusion) on Day 1, 24 hours post-infusion on Day 2, at any time on Day 8 and pre-dose sample on Day 15
Terminal Elimination Half-life (t1/2) of NC410
Terminal elimination half-life, in hours, calculated as 0.693/λz after each dose administration at Cycle 1. Note partipants enrolled at 200mg dose level were dosed with 100mg of NC410 at Cycle 1 Day 1.
Time frame: PK samples collected pre-dose, 30 minutes post-NC410 infusion (end of infusion) on Day 1, 24 hours post-infusion on Day 2, at any time on Day 8 and pre-dose sample on Day 15
Area Under the Serum Concentration Versus Time Curve (AUC) of NC410
Area under the curve from the time of dosing to the time of the last measurable concentration at Cycle 1 Day 1.
Time frame: Time of dosing to the time of the last measurable PK concentration at Cycle 1 Day 1. Samples taken pre-dose and 30-min post dose at Cycle 1 Day 1.
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