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

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)

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

Study Overview

• Status: Recruiting
• Conditions: Advanced or Metastatic Solid Tumor
• Intervention / Treatment: Drug: PLN-101095; Drug: PLN-101095; Drug: PLN-101095; Drug: PLN-101095; Drug: PLN-101095; Drug: PLN-101095; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 124
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Pliant Therapeutics Medical Monitor; Phone Number: clintrials@pliantrx.com; Email: clintrials@pliantrx.com

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Active, not recruiting
      • Yale University
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute of Emory University
      • Contact: Pliant Therapeutics Medical Monitor; Email: clintrials@pliantrx.com
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • South Texas Accelerated Research Therapeutics (START)
      • Contact: Pliant Therapeutics Medical Monitor; Email: clintrials@pliantrx.com
  • Texas
    • Austin, Texas, United States, 78758
      • Recruiting
      • NEXT Austin
      • Contact: Pliant Therapeutics Medical Monitor; Email: clintrials@pliantrx.com
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas MD Anderson Cancer Center
      • Contact: Pliant Therapeutics Medical Monitor; Email: clintrials@pliantrx.com
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Virginia
      • Contact: Pliant Therapeutics Medical Monitor; Email: clintrials@pliantrx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Dose Escalation - 250 mg BID; Cohort 1 PLN-101095 250 mg BID in combination with pembrolizumab in participants with solid tumors	Drug: PLN-101095; PLN-101095; Drug: PLN-101095; PLN-101095 250 mg BID; Drug: PLN-101095; PLN-101095 500 mg BID; Drug: PLN-101095; PLN-101095 1000 mg BID; Drug: PLN-101095; PLN-101095 1000 mg TID; Drug: PLN-101095; PLN-101095 2000 mg BID; Drug: Pembrolizumab; Pembrolizumab (KEYTRUDA) 200 mg IV Q3W
Experimental: Part 1 Dose Escalation - 500 mg BID; PLN-101095 500 mg BID in combination with pembrolizumab in participants with solid tumors	Drug: PLN-101095; PLN-101095; Drug: PLN-101095; PLN-101095 250 mg BID; Drug: PLN-101095; PLN-101095 500 mg BID; Drug: PLN-101095; PLN-101095 1000 mg BID; Drug: PLN-101095; PLN-101095 1000 mg TID; Drug: PLN-101095; PLN-101095 2000 mg BID; Drug: Pembrolizumab; Pembrolizumab (KEYTRUDA) 200 mg IV Q3W
Experimental: Part 1 Dose Escalation - 1000 mg BID; PLN-101095 1000 mg BID in combination with pembrolizumab in participants with solid tumors	Drug: PLN-101095; PLN-101095; Drug: PLN-101095; PLN-101095 250 mg BID; Drug: PLN-101095; PLN-101095 500 mg BID; Drug: PLN-101095; PLN-101095 1000 mg BID; Drug: PLN-101095; PLN-101095 1000 mg TID; Drug: PLN-101095; PLN-101095 2000 mg BID; Drug: Pembrolizumab; Pembrolizumab (KEYTRUDA) 200 mg IV Q3W
Experimental: Part 1 Dose Escalation - 1000 mg TID; PLN-101095 1000 mg TID in combination with pembrolizumab in participants with solid tumors	Drug: PLN-101095; PLN-101095; Drug: PLN-101095; PLN-101095 250 mg BID; Drug: PLN-101095; PLN-101095 500 mg BID; Drug: PLN-101095; PLN-101095 1000 mg BID; Drug: PLN-101095; PLN-101095 1000 mg TID; Drug: PLN-101095; PLN-101095 2000 mg BID; Drug: Pembrolizumab; Pembrolizumab (KEYTRUDA) 200 mg IV Q3W
Experimental: Part 1 Dose Escalation - 2000 mg BID; PLN-101095 2000 mg BID in combination with pembrolizumab in participants with solid tumors	Drug: PLN-101095; PLN-101095; Drug: PLN-101095; PLN-101095 250 mg BID; Drug: PLN-101095; PLN-101095 500 mg BID; Drug: PLN-101095; PLN-101095 1000 mg BID; Drug: PLN-101095; PLN-101095 1000 mg TID; Drug: PLN-101095; PLN-101095 2000 mg BID; Drug: Pembrolizumab; Pembrolizumab (KEYTRUDA) 200 mg IV Q3W
Experimental: Part 2 Dose Expansion - NSCLC; PLN-101095 given as monotherapy and in combination with pembrolizumab in participants with Non-small cell lung cancer (NSCLC)	Drug: PLN-101095; PLN-101095; Drug: PLN-101095; PLN-101095 250 mg BID; Drug: PLN-101095; PLN-101095 500 mg BID; Drug: PLN-101095; PLN-101095 1000 mg BID; Drug: PLN-101095; PLN-101095 1000 mg TID; Drug: PLN-101095; PLN-101095 2000 mg BID; Drug: Pembrolizumab; Pembrolizumab (KEYTRUDA) 200 mg IV Q3W
Experimental: Part 2 Dose Expansion - ccRCC; PLN-101095 given as monotherapy and in combination with pembrolizumab in participants with Clear cell renal cell carcinoma (ccRCC)	Drug: PLN-101095; PLN-101095; Drug: PLN-101095; PLN-101095 250 mg BID; Drug: PLN-101095; PLN-101095 500 mg BID; Drug: PLN-101095; PLN-101095 1000 mg BID; Drug: PLN-101095; PLN-101095 1000 mg TID; Drug: PLN-101095; PLN-101095 2000 mg BID; Drug: Pembrolizumab; Pembrolizumab (KEYTRUDA) 200 mg IV Q3W
Experimental: Part 2 Dose Expansion - TMB-high solid tumors; PLN-101095 given as monotherapy and in combination with pembrolizumab in participants with Tumor mutational burden (TMB)-high solid tumors	Drug: PLN-101095; PLN-101095; Drug: PLN-101095; PLN-101095 250 mg BID; Drug: PLN-101095; PLN-101095 500 mg BID; Drug: PLN-101095; PLN-101095 1000 mg BID; Drug: PLN-101095; PLN-101095 1000 mg TID; Drug: PLN-101095; PLN-101095 2000 mg BID; Drug: Pembrolizumab; Pembrolizumab (KEYTRUDA) 200 mg IV Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	First dose to disease progression or death from any cause, whichever occurs first.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK of PLN-101095 monotherapy in Parts 1 and 2	Maximum drug concentration (Cmax)	Day 14, 0 to up to 12 hours
PK of PLN-101095 monotherapy in Parts 1 and 2	Time to Cmax (Tmax)	Day 14, 0 to up to 12 hours
PK of PLN-101095 monotherapy in Parts 1 and 2	Area under the concentration-time curve (AUC0-τ)	Day 14, 0 to up to 12 hours
Duration of anti-tumor activity of PLN-101095 in combination with pembrolizumab in Part 2	Duration of response (DOR) for objective responders	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 on treatment (TOT) for objective responders	First dose to progression or death from any cause, whichever occurs first

Collaborators and Investigators

• Sponsor: Pliant Therapeutics, Inc.
• Investigators: Study Director: Pliant Therapeutics Medical Monitor, Pliant Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2023
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: January 26, 2024
• First Submitted That Met QC Criteria: February 13, 2024
• First Posted (Actual): February 21, 2024

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Urothelial Carcinoma; Immunotherapy; Pembrolizumab; Melanoma; Colorectal Cancer; Endometrial Cancer; Non-small cell lung cancer (NSCLC); Cholangiocarcinoma; Advanced Solid Tumors Cancer; Gallbladder; Ovarian Carcinoma; Triple Negative Breast Cancer (TNBC); Anal Carcinoma; Clear cell renal cell carcinoma (ccRCC); Biliary tract carcinoma (BTC); Head and Neck Squamous Cell Cancer (HNSCC); Tumor mutational burden (TMB)-high tumors; TMB-low tumors
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Neoplastic Processes; Lung Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Urologic Neoplasms; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Uterine Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Breast Neoplasms; Anus Diseases; Rectal Neoplasms; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Colorectal Neoplasms; Ovarian Neoplasms; Neoplasm Metastasis; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Cholangiocarcinoma; Melanoma; Triple Negative Breast Neoplasms; Endometrial Neoplasms; Carcinoma, Transitional Cell; Anus Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; pembrolizumab
• Other Study ID Numbers: PLN-101095-ONC-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No