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 * Part 2: Dose-expansion cohorts using Simon's 2-stage design
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
77
PLN-101095
Pembrolizumab
Yale University
New Haven, Connecticut, 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
RECRUITINGProportion of participants with treatment-emergent adverse events and serious adverse events per CTCAE Version 5.0.
Time frame: Signing ICF until 16 weeks after end of study treatment regimen
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
Maximum observed plasma concentration (Cmax) to characterize the plasma pharmacokinetics (PK).
Time frame: First dose until 10 weeks
Time to maximum observed concentration (Tmax) to characterize the plasma pharmacokinetics (PK).
Time frame: First dose until 10 weeks
Area under the concentration-time curve over a dosing interval (AUC0-τ) to characterize the plasma pharmacokinetics (PK).
Time frame: First dose until 10 weeks
Disease control rate (DCR) is defined by the proportion of participants who maintain disease control (iCR, iPR or iSD) per iRECIST Version 1.1.
Time frame: Day 1 until end of study treatment regimen
Objective response rate (ORR) is defined by the proportion of participants with an iCR or iPR per iRECIST Version 1.1.
Time frame: Day 1 until end of study treatment regimen
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