Health TrialsbyHealthPanel

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

ConditionAdvanced or Metastatic Solid Tumor
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorPliant Therapeutics, Inc.

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Sequential

Treatments tested in this trial

  • PLN-101095

    Drug

    PLN-101095 250 mg BID

  • PLN-101095

    Drug

    PLN-101095 500 mg BID

  • PLN-101095

    Drug

    PLN-101095 1000 mg BID

  • PLN-101095

    Drug

    PLN-101095 1000 mg TID

  • PLN-101095

    Drug

    PLN-101095 2000 mg BID

  • PLN-101095

    Drug

    PLN-101095

  • Pembrolizumab

    Drug

    Pembrolizumab (KEYTRUDA) 200 mg IV Q3W

Treatment groups

124 Participants
are divided into 8 treatment groups

8

Treatment groups

See each treatment group below.

Group A: Part 1 Dose Escalation - 250 mg BIDExperimental treatment 2 interventions
Group B: Part 1 Dose Escalation - 500 mg BIDExperimental treatment 2 interventions
Group C: Part 1 Dose Escalation - 1000 mg BIDExperimental treatment 2 interventions
Group D: Part 1 Dose Escalation - 1000 mg TIDExperimental treatment 2 interventions
Group E: Part 1 Dose Escalation - 2000 mg BIDExperimental treatment 2 interventions
Group F: Part 2 Dose Expansion - NSCLCExperimental treatment 2 interventions
Group G: Part 2 Dose Expansion - ccRCCExperimental treatment 2 interventions
Group H: Part 2 Dose Expansion - TMB-high solid tumorsExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
First dose to 35 days
2

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.

Time frame
Day 1 until 16 weeks after end of study treatment regimen
3

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.

Time frame
First dose to disease progression or death from any cause, whichever occurs first.
4

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.

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

Secondary outcomes

1

PK of PLN-101095 monotherapy in Parts 1 and 2

Maximum drug concentration (Cmax)

Time frame
Day 14, 0 to up to 12 hours
2

PK of PLN-101095 monotherapy in Parts 1 and 2

Time to Cmax (Tmax)

Time frame
Day 14, 0 to up to 12 hours
3

PK of PLN-101095 monotherapy in Parts 1 and 2

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

Time frame
Day 14, 0 to up to 12 hours
4

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

Duration of response (DOR) for objective responders

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Pliant Therapeutics, Inc.

Lead sponsor

Source ClinicalTrials.gov
Apply now