This is a Phase 1a/1b, dose-escalation/expansion, consecutive-cohort, open-label study to evaluate the safety, tolerability, PK, PD, and preliminary evidence of antitumor activity of PLN-101095 in combination with pembrolizumab (the study treatment regimen) in adult participants with advanced or metastatic solid tumors for which pembrolizumab is indicated but have documented disease progression (refractory \[primary resistance\]) or relapsed \[secondary resistance\]) after at least 3 months from the start of treatment with pembrolizumab. The study will consist of 2 main parts: * Part 1: Consecutive dose-escalation cohorts using a Bayesian optimal interval (BOIN) dose escalation design with accelerated titration * Part 2: Dose-expansion cohorts using Simon's 2-stage design
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
124
PLN-101095 250 mg BID
PLN-101095 500 mg BID
PLN-101095 1000 mg BID
PLN-101095 1000 mg TID
PLN-101095 2000 mg BID
PLN-101095
Pembrolizumab (KEYTRUDA) 200 mg IV Q3W
Yale University
New Haven, Connecticut, United States
ACTIVE_NOT_RECRUITINGWinship Cancer Institute of Emory University
Atlanta, Georgia, United States
RECRUITINGSouth Texas Accelerated Research Therapeutics (START)
Grand Rapids, Michigan, United States
RECRUITINGNEXT Austin
Austin, Texas, United States
RECRUITINGUniversity of Texas MD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGNEXT Virginia
Fairfax, Virginia, United States
RECRUITINGSafety and tolerability of PLN-101095 in combination with pembrolizumab in Parts 1 and 2
Number of participants with a Dose Limiting Toxicity (DLT) defined as toxicities that meet predefined severity criteria, assess as having a suspected relationship to study drug, unrelated to disease, inter-current illness, or concomitant medications.
Time frame: First dose to 35 days
Safety and tolerability of PLN-101095 in combination with pembrolizumab in Parts 1 and 2
Proportion of participants with treatment-emergent adverse events and serious adverse events.
Time frame: Day 1 until 16 weeks after end of study treatment regimen
Anti-tumor activity of PLN-101095 in combination with pembrolizumab in Part 2
Proportion of participants achieving confirmed iPR or iCR per iRECIST Version 1.1.
Time frame: First dose to disease progression or death from any cause, whichever occurs first.
Anti-tumor activity of PLN-101095 in combination with pembrolizumab in Part 2
Proportion of participants who maintain disease control (iCR, iPR or iSD) per iRECIST Version 1.1.
Time frame: First dose to disease progression or death from any cause, whichever occurs first.
PK of PLN-101095 monotherapy in Parts 1 and 2
Maximum drug concentration (Cmax)
Time frame: Day 14, 0 to up to 12 hours
PK of PLN-101095 monotherapy in Parts 1 and 2
Time to Cmax (Tmax)
Time frame: Day 14, 0 to up to 12 hours
PK of PLN-101095 monotherapy in Parts 1 and 2
Area under the concentration-time curve (AUC0-τ)
Time frame: Day 14, 0 to up to 12 hours
Duration of anti-tumor activity of PLN-101095 in combination with pembrolizumab in Part 2
Duration of response (DOR) for objective responders
Time frame: First objective response (CR or PR) to disease progression or death from any cause, whichever occurs first
Duration of anti-tumor activity of PLN-101095 in combination with pembrolizumab in Part 2
Time on treatment (TOT) for objective responders
Time frame: First dose to progression or death from any cause, whichever occurs first
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