Advanced or Metastatic Solid Tumor
Conditions
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
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
Interventions
DRUGPLN-101095
PLN-101095 250 mg BID
DRUGPembrolizumab
Pembrolizumab (KEYTRUDA) 200 mg IV Q3W
Sponsors
Pliant Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has histologically or cytologically confirmed advanced or metastatic solid tumor 2. Have received ≥12 weeks of continuous anti-PD-1 or anti-PD-L1 treatment administered as monotherapy or in combination with other anticancer therapies 3. Have demonstrated documented prior clinical benefit, defined as CR or PR at any time during treatment, or SD lasting ≥6 months (Part 2 only) 4. 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 5. At least 1 measurable lesion, as defined by RECIST v1.1 6. Estimated survival of ≥3 months 7. Have adequate bone marrow and organ function. 8. A female participant is eligible to participate if she is not pregnant, not breastfeeding
Exclusion criteria
1. Any immune-related medical conditions that would put participants at greater risk when receiving pembrolizumab 2. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years 3. Has received prior radiotherapy within 2 weeks for palliative bone-directed therapy and 4 weeks for all other radiotherapy 4. 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 5. Has a diagnosis of immunodeficiency or use of systemic steroids \>10 mg/day 6. Has an active autoimmune disease that has required systemic treatment in the past 2 years 7. Has known active CNS metastases (brain and/or leptomeningeal metastases) 8. Has significant cardiac disease 9. Has an active infection requiring systemic therapy (including uncontrolled HIV, Hepatitis B and C) 10. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of PLN-101095 in combination with pembrolizumab in Parts 1 and 2 | First dose to 35 days | 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. |
| Anti-tumor activity of PLN-101095 in combination with pembrolizumab in Part 2 | First dose to disease progression or death from any cause, whichever occurs first. | Proportion of participants achieving confirmed iPR or iCR per iRECIST Version 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK of PLN-101095 monotherapy in Parts 1 and 2 | Day 14, 0 to up to 12 hours | Maximum drug concentration (Cmax) |
| 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 response (DOR) for objective responders |
Countries
United States
Contacts
CONTACTPliant Therapeutics Medical Monitor
STUDY_DIRECTORPliant Therapeutics Medical Monitor
Pliant Therapeutics, Inc.
Outcome results
None listed