A Phase 1a/1b Multicenter, Open-label Dose Escalation/Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of PLN-101095 as Monotherapy and in Combination With Pembrolizumab in Adult Participants With Advanced or Metastatic Solid Tumors Who Have Disease Progression While on an Immune Checkpoint Inhibitor (FORTIFY)
Summary
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
Arms & interventions
- DrugPLN-101095
PLN-101095 250 mg BID
- DrugPLN-101095
PLN-101095 500 mg BID
- DrugPLN-101095
PLN-101095 1000 mg BID
- DrugPLN-101095
PLN-101095 1000 mg TID
- DrugPLN-101095
PLN-101095 2000 mg BID
- DrugPLN-101095
PLN-101095
- DrugPembrolizumab
Pembrolizumab (KEYTRUDA) 200 mg IV Q3W
Outcome measures
Primary
Safety 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.
Secondary
PK of PLN-101095 monotherapy in Parts 1 and 2
Time frame: Day 14, 0 to up to 12 hours
PK of PLN-101095 monotherapy in Parts 1 and 2
Time frame: Day 14, 0 to up to 12 hours
PK of PLN-101095 monotherapy in Parts 1 and 2
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
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 frame: First dose to progression or death from any cause, whichever occurs first
Eligibility criteria
Study locations (6)
Yale University
New Haven, Connecticut, 06511
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
South Texas Accelerated Research Therapeutics (START)
Grand Rapids, Michigan, 49546
NEXT Austin
Austin, Texas, 78758
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
NEXT Virginia
Fairfax, Virginia, 22031