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 an Immune Checkpoint Inhibitor (FORTIFY)

Overview

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

Interventions

• 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 PLN-101095
  PLN-101095
• Drug Pembrolizumab
  Pembrolizumab (KEYTRUDA) 200 mg IV Q3W

Primary outcome measures

• Safety and tolerability of PLN-101095 in combination with pembrolizumab in Parts 1 and 2 [Time frame: First dose to 35 days]
• 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]
• 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.]
• 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.]

Secondary outcome measures (5)

• PK of PLN-101095 monotherapy in Parts 1 and 2 [Time frame: Day 14, 0 to up to 12 hours]
• PK of PLN-101095 monotherapy in Parts 1 and 2 [Time frame: Day 14, 0 to up to 12 hours]
• PK of PLN-101095 monotherapy in Parts 1 and 2 [Time frame: Day 14, 0 to up to 12 hours]
• 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 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]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 12 centers

• Yale University — New Haven
• Winship Cancer Institute of Emory University — Atlanta
• South Texas Accelerated Research Therapeutics (START) — Grand Rapids
• START New Jersey — East Brunswick
• START New York Long Island LLC — Lake Success
• Carolina Cancer Research Center — Wilson
• NEXT Austin — Austin
• START Center for Clinical Research — Fort Worth
• … and 4 more centers

Identifiers

NCT: NCT06270706 · PLN-101095-ONC-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗