Clinical trial NCT06270706: A Phase 1 Study of PLN-101095 in Adults With Advanced or Metastatic Solid Tumors
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 Pembrolizumab
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metastatic Solid Tumor
Keywords: Advanced Solid Tumors Cancer
Head and Neck Squamous Cell Cancer
Colorectal Cancer
Urothelial Carcinoma
Gastro-esophageal Junction Cancers
Esophageal Cancer
Cervical Cancer
Hepatocellular Carcinoma
Renal Cell Carcinoma
Endometrial Cancer
Cutaneous Squamous Cell Carcinoma
Triple Negative Breast Cancer
Melanoma
Non-Squamous Cell Lung Cancer
Lead sponsor: Pliant Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-02-21
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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
* Part 2: Dose-expansion cohorts using Simon's 2-stage design


Eligibility criteria: Inclusion Criteria:

1. Has histologically or cytologically confirmed advanced solid tumor
2. Has an advanced or metastatic solid tumor (for which pembrolizumab is indicated) and have evidence of disease progression after treatment with pembrolizumab.
3. At least 1 measurable lesion, as defined by RECIST v1.1
4. Estimated survival of ≥3 months
5. No effective therapeutic options available (eg, has received standard of care or is intolerant of, refuses, or is not eligible for standard of care antineoplastic therapy)

Exclusion Criteria:

1. Any immune-related medical conditions that would put participants at greater risk when receiving pembrolizumab
2. Previous treatment with pembrolizumab \<21 days prior to the first dose of combination therapy of pembrolizumab and PLN-101095
3. Received an immunotherapy other than pembrolizumab in the last 4 weeks prior to the first dose of PLN-101095
4. Received radiotherapy (RT) within 1 week for palliative bone-directed therapy and 4 weeks for all other types, prior to the first dose of PLN-101095
5. Received chemotherapy or other targeted therapies within 2 weeks prior to the first dose of PLN-101095
6. Received a cell therapy within the last 12 months prior to the first dose of PLN-101095
7. Known active central nervous system (CNS) metastases (brain and/or leptomeningeal metastases)
8. Pregnant or lactating female participant

Primary outcomes:
measure: Proportion of participants with treatment-emergent adverse events and serious adverse events per CTCAE Version 5.0.
timeFrame: Signing ICF until 16 weeks after end of study treatment regimen
measure: 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.
timeFrame: First dose to 35 days
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax) to characterize the plasma pharmacokinetics (PK).
timeFrame: First dose until 10 weeks
measure: Time to maximum observed concentration (Tmax) to characterize the plasma pharmacokinetics (PK).
timeFrame: First dose until 10 weeks
measure: Area under the concentration-time curve over a dosing interval (AUC0-τ) to characterize the plasma pharmacokinetics (PK).
timeFrame: First dose until 10 weeks
measure: Disease control rate (DCR) is defined by the proportion of participants who maintain disease control (iCR, iPR or iSD) per iRECIST Version 1.1.
timeFrame: Day 1 until end of study treatment regimen
measure: Objective response rate (ORR) is defined by the proportion of participants with an iCR or iPR per iRECIST Version 1.1.
timeFrame: Day 1 until end of study treatment regimen
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Grand Rapids
country: United States
facility: South Texas Accelerated Research Therapeutics (START)
state: Michigan
city: Austin
country: United States
facility: NEXT Austin
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
Study officials:
affiliation: Pliant Therapeutics, Inc.
name: Pliant Therapeutics Medical Monitor
role: STUDY_DIRECTOR
References: