Clinical Trial Details
Back to clinical trials
Phase IInterventional
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)
Protocol: STUDY00006985NCT: NCT06270706
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
Eligibility
| Ages | 18 Years and older |
| Sex | All |
| Healthy Volunteers | No |
| Age Groups | Adult, Older Adult |
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
