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

NCT06270706
clinicaltrials.gov
Phase
Phase 1
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Recruitment status
Recruiting
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Participants
124
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Lead sponsor
Pliant Therapeutics, Inc.
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Start date
2023-08-30
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Number of sites
22
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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
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Short title
A Phase 1 Study of PLN-101095 in Adults With Advanced or Metastatic Solid Tumors
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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)
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2030-06-01
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First posted
2024-02-21
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Registry last updated
2026-10-02
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Primary completion date
2030-06-01
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Start date
2023-08-30
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Participants
124
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Participant count basis
Estimated
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Planned participants
124
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Protocol amendments
1
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Number of sites
22
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Pliant Therapeutics, Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06270706
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ClinicalTrials.gov ID
NCT06270706
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Safety and tolerability of PLN-101095 in combination with pembrolizumab in Parts 1 and 2

    Timeframe: First dose to 35 days

    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.

  2. Safety and tolerability of PLN-101095 in combination with pembrolizumab in Parts 1 and 2

    Timeframe: Day 1 until 16 weeks after end of study treatment regimen

    Proportion of participants with treatment-emergent adverse events and serious adverse events.

  3. Anti-tumor activity of PLN-101095 in combination with pembrolizumab in Part 2

    Timeframe: First dose to disease progression or death from any cause, whichever occurs first.

    Proportion of participants achieving confirmed iPR or iCR per iRECIST Version 1.1.

  4. Anti-tumor activity of PLN-101095 in combination with pembrolizumab in Part 2

    Timeframe: First dose to disease progression or death from any cause, whichever occurs first.

    Proportion of participants who maintain disease control (iCR, iPR or iSD) per iRECIST Version 1.1.

  1. PK of PLN-101095 monotherapy in Parts 1 and 2

    Timeframe: Day 14, 0 to up to 12 hours

    Maximum drug concentration (Cmax)

  2. PK of PLN-101095 monotherapy in Parts 1 and 2

    Timeframe: Day 14, 0 to up to 12 hours

    Time to Cmax (Tmax)

  3. PK of PLN-101095 monotherapy in Parts 1 and 2

    Timeframe: Day 14, 0 to up to 12 hours

    Area under the concentration-time curve (AUC0-τ)

  4. Duration of anti-tumor activity of PLN-101095 in combination with pembrolizumab in Part 2

    Timeframe: First objective response (CR or PR) to disease progression or death from any cause, whichever occurs first

    Duration of response (DOR) for objective responders

  5. Duration of anti-tumor activity of PLN-101095 in combination with pembrolizumab in Part 2

    Timeframe: First dose to progression or death from any cause, whichever occurs first

    Time on treatment (TOT) for objective responders

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  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

  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
Sources for eligibility
clinicaltrials.gov

  • Yale UniversityNew Haven, United StatesCompleted
  • Winship Cancer Institute of Emory UniversityAtlanta, United StatesRecruiting
  • South Texas Accelerated Research Therapeutics (START)Grand Rapids, United StatesRecruiting
  • Washington University MedicineSt Louis, United StatesRecruiting
  • START New JerseyEast Brunswick, United StatesRecruiting
  • START New York Long Island LLCLake Success, United StatesRecruiting
  • Carolina Cancer Research CenterWilson, United StatesRecruiting
  • Avera Medical GroupSioux Falls, United StatesRecruiting
  • Tennessee OncologyNashville, United StatesRecruiting
  • NEXT AustinAustin, United StatesRecruiting
  • START Center for Clinical ResearchFort Worth, United StatesRecruiting
  • University of Texas MD Anderson Cancer CenterHouston, United StatesRecruiting
  • NEXT HoustonHouston, United StatesRecruiting
  • START Mountain RegionWest Valley City, United StatesRecruiting
  • Inova Schar Cancer InstituteFairfax, United StatesRecruiting
  • NEXT VirginiaFairfax, United StatesRecruiting
  • Hospital Universitari Quirónsalud (NEXT Barcelona)Barcelona, SpainRecruiting
  • START Barcelona - Hospital HM Nou DelfosBarcelona, SpainRecruiting
  • START Center for Cancer Research - La RiojaLogroño, SpainRecruiting
  • START Madrid - Hospital Universitario Fundación Jiménez DíazMadrid, SpainRecruiting
  • START Madrid - Centro Integral Oncológico Clara CampalMadrid, SpainRecruiting
  • University Hospital Quironsalud Madrid (NEXT Madrid)Madrid, SpainRecruiting
Sources for sites
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (11)

Targets (1)