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

NCT06270706 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PLN-101095-ONC-101
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 6

Brief 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

Conditions

Advanced or Metastatic Solid Tumor

Keywords

Advanced Solid Tumors Cancer; Anal Carcinoma; Biliary tract carcinoma (BTC); Cholangiocarcinoma; Clear cell renal cell carcinoma (ccRCC); Colorectal Cancer; Endometrial Cancer; Gallbladder; Head and Neck Squamous Cell Cancer (HNSCC); Melanoma; Non-small cell lung cancer (NSCLC); Ovarian Carcinoma; Triple Negative Breast Cancer (TNBC); Tumor mutational burden (TMB)-high tumors; TMB-low tumors; Urothelial Carcinoma; Pembrolizumab; Immunotherapy

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (5)

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

  Day 14, 0 to up to 12 hours

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

  Day 14, 0 to up to 12 hours

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

  Day 14, 0 to up to 12 hours

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

  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

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

Study Arms (8)

Part 1 Dose Escalation - 250 mg BID

EXPERIMENTAL

Cohort 1 PLN-101095 250 mg BID in combination with pembrolizumab in participants with solid tumors

Drug: PLN-101095; Drug: Pembrolizumab

Part 1 Dose Escalation - 500 mg BID

EXPERIMENTAL

PLN-101095 500 mg BID in combination with pembrolizumab in participants with solid tumors

Drug: PLN-101095; Drug: Pembrolizumab

Part 1 Dose Escalation - 1000 mg BID

EXPERIMENTAL

PLN-101095 1000 mg BID in combination with pembrolizumab in participants with solid tumors

Drug: PLN-101095; Drug: Pembrolizumab

Part 1 Dose Escalation - 1000 mg TID

EXPERIMENTAL

PLN-101095 1000 mg TID in combination with pembrolizumab in participants with solid tumors

Drug: PLN-101095; Drug: Pembrolizumab

Part 1 Dose Escalation - 2000 mg BID

EXPERIMENTAL

PLN-101095 2000 mg BID in combination with pembrolizumab in participants with solid tumors

Drug: PLN-101095; Drug: Pembrolizumab

Part 2 Dose Expansion - NSCLC

EXPERIMENTAL

PLN-101095 given as monotherapy and in combination with pembrolizumab in participants with Non-small cell lung cancer (NSCLC)

Drug: PLN-101095; Drug: Pembrolizumab

Part 2 Dose Expansion - ccRCC

EXPERIMENTAL

PLN-101095 given as monotherapy and in combination with pembrolizumab in participants with Clear cell renal cell carcinoma (ccRCC)

Drug: PLN-101095; Drug: Pembrolizumab

Part 2 Dose Expansion - TMB-high solid tumors

EXPERIMENTAL

PLN-101095 given as monotherapy and in combination with pembrolizumab in participants with Tumor mutational burden (TMB)-high solid tumors

Drug: PLN-101095; Drug: Pembrolizumab

Interventions

PLN-101095 DRUG

PLN-101095 250 mg BID

Part 1 Dose Escalation - 250 mg BID

Pembrolizumab DRUG

Pembrolizumab (KEYTRUDA) 200 mg IV Q3W

Part 1 Dose Escalation - 1000 mg BID; Part 1 Dose Escalation - 1000 mg TID; Part 1 Dose Escalation - 2000 mg BID; Part 1 Dose Escalation - 250 mg BID; Part 1 Dose Escalation - 500 mg BID; Part 2 Dose Expansion - NSCLC; Part 2 Dose Expansion - TMB-high solid tumors; Part 2 Dose Expansion - ccRCC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pliant Therapeutics, Inc.: lead

Study Sites (6)

Yale University

New Haven, Connecticut, 06511, United States

ACTIVE NOT RECRUITING

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

South Texas Accelerated Research Therapeutics (START)

Grand Rapids, Michigan, 49546, United States

RECRUITING

NEXT Austin

Austin, Texas, 78758, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Anus Neoplasms; Cholangiocarcinoma; Carcinoma, Renal Cell; Colorectal Neoplasms; Endometrial Neoplasms; Melanoma; Carcinoma, Non-Small-Cell Lung; Ovarian Neoplasms; Triple Negative Breast Neoplasms; Carcinoma, Transitional Cell

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Rectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Colonic Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Genital Diseases, Female; Genital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Neoplasms; Breast Diseases

Study Officials

• Pliant Therapeutics Medical Monitor

  Pliant Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

Pliant Therapeutics Medical Monitor

CONTACT

clintrials@pliantrx.com; clintrials@pliantrx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2024
• First Posted: February 21, 2024
• Study Start: August 30, 2023
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (6)