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NCT Number: NCT06270706

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

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

Recruiting

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Key information

Conditions

Advanced or Metastatic Solid Tumor Adenocarcinoma Adnexal Diseases Anus Diseases Anus Neoplasms Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Carcinoma, Renal Cell Carcinoma, Transitional Cell Cholangiocarcinoma Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Endometrial Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastrointestinal Diseases Gastrointestinal Neoplasms Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Intestinal Diseases Intestinal Neoplasms Kidney Diseases Kidney Neoplasms Lung Diseases Lung Neoplasms Male Urogenital Diseases Melanoma Neoplasm Metastasis Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplastic Processes Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Ovarian Diseases Ovarian Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Rectal Diseases Rectal Neoplasms Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Thoracic Neoplasms Triple Negative Breast Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Yale University, New Haven, Connecticut, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Has histologically or cytologically confirmed advanced or metastatic solid tumor
  • Have received ≥12 weeks of continuous anti-PD-1 or anti-PD-L1 treatment administered as monotherapy or in combination with other anticancer therapies
  • Have demonstrated documented prior clinical benefit, defined as CR or PR at any time during treatment, or SD lasting ≥6 months (Part 2 only)
  • 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
  • At least 1 measurable lesion, as defined by RECIST v1.1
  • Estimated survival of ≥3 months
  • Have adequate bone marrow and organ function.
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding

Exclusion criteria

  • Any immune-related medical conditions that would put participants at greater risk when receiving pembrolizumab
  • Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
  • Has received prior radiotherapy within 2 weeks for palliative bone-directed therapy and 4 weeks for all other radiotherapy
  • 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
  • Has a diagnosis of immunodeficiency or use of systemic steroids >10 mg/day
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years
  • Has known active CNS metastases (brain and/or leptomeningeal metastases)
  • Has significant cardiac disease
  • Has an active infection requiring systemic therapy (including uncontrolled HIV, Hepatitis B and C)
  • 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

Treatment and study plan

PLN-101095

Drug

PLN-101095 250 mg BID

Pembrolizumab

Drug

Pembrolizumab (KEYTRUDA) 200 mg IV Q3W

Primary outcomes

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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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.

Secondary outcomes

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

    Time frame: Day 14, 0 to up to 12 hours

    Maximum drug concentration (Cmax)

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

    Time frame: Day 14, 0 to up to 12 hours

    Time to Cmax (Tmax)

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

    Time frame: 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

    Time frame: 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

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

    Time on treatment (TOT) for objective responders

Study contacts

Contact information is provided by the study sponsor or research team.

Pliant Therapeutics Medical Monitor

CONTACT

[email protected]

[email protected]

Sponsors and collaborators

Lead sponsor

Pliant Therapeutics, Inc.

Industry

Registry information

Official study 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)

Important dates

Study start
2023
Primary completion
2030
Study completion
2030
First posted
Feb 21, 2024
Registry last updated
Apr 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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