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A Phase 1 Study of PLN-101095 in Adults With Advanced or Metastatic Solid Tumors

NCT06270706 · Pliant Therapeutics, Inc.
In plain English

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Official title
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)
About this study
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
Eligibility criteria
Inclusion Criteria: 1. Has histologically or cytologically confirmed advanced or metastatic solid tumor 2. Have received ≥12 weeks of continuous anti-PD-1 or anti-PD-L1 treatment administered as monotherapy or in combination with other anticancer therapies 3. Have demonstrated documented prior clinical benefit, defined as CR or PR at any time during treatment, or SD lasting ≥6 months (Part 2 only) 4. Must have subsequently developed radiographic disease progression while receiving anti-PD-1 or anti-PD-L1 treatment or within ≤12 weeks after the last dose of such treatment 5. At least 1 measurable lesion, as defined by RECIST v1.1 6. Estimated survival of ≥3 months 7. Have adequate bone marrow and organ function. 8. A female participant is eligible to participate if she is not pregnant, not breastfeeding Exclusion Criteria: 1. Any immune-related medical conditions that would put participants at greater risk when receiving pembrolizumab 2. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years 3. Has received prior radiotherapy within 2 weeks for palliative bone-directed therapy and 4 weeks for all other radiotherapy 4. Has undergone major surgery within 4 weeks prior to the first dose of study treatment or has not adequately recovered from surgery or related complications 5. Has a diagnosis of immunodeficiency or use of systemic steroids \>10 mg/day 6. Has an active autoimmune disease that has required systemic treatment in the past 2 years 7. Has known active CNS metastases (brain and/or leptomeningeal metastases) 8. Has significant cardiac disease 9. Has an active infection requiring systemic therapy (including uncontrolled HIV, Hepatitis B and C) 10. Has received a live or live-attenuated vaccine within 30 days or a non-live vaccine within 7 days prior to the first dose of PLN-101095
Study design
Enrollment target: 124 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2023-08-30
Estimated completion: 2030-06
Last updated: 2026-04-20
Interventions
Drug: PLN-101095Drug: PLN-101095Drug: PLN-101095Drug: PLN-101095Drug: PLN-101095Drug: PLN-101095Drug: Pembrolizumab
Primary outcomes
  • Safety and tolerability of PLN-101095 in combination with pembrolizumab in Parts 1 and 2 (First dose to 35 days)
  • Safety and tolerability of PLN-101095 in combination with pembrolizumab in Parts 1 and 2 (Day 1 until 16 weeks after end of study treatment regimen)
  • Anti-tumor activity of PLN-101095 in combination with pembrolizumab in Part 2 (First dose to disease progression or death from any cause, whichever occurs first.)
Sponsor
Pliant Therapeutics, Inc. · industry
Contacts & investigators
ContactPliant Therapeutics Medical Monitor · contact · clintrials@pliantrx.com · clintrials@pliantrx.com
InvestigatorPliant Therapeutics Medical Monitor · study_director, Pliant Therapeutics, Inc.
All locations (6)
Yale UniversityActive Not Recruiting
New Haven, Connecticut, United States
Winship Cancer Institute of Emory UniversityRecruiting
Atlanta, Georgia, United States
South Texas Accelerated Research Therapeutics (START)Recruiting
Grand Rapids, Michigan, United States
NEXT AustinRecruiting
Austin, Texas, United States
University of Texas MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
NEXT VirginiaRecruiting
Fairfax, Virginia, United States
A Phase 1 Study of PLN-101095 in Adults With Advanced or Metastatic Solid Tumors · TrialPath