A Phase 1a/1b FIH Study of PY159 and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
- Conditions
- Gastric AdenocarcinomaColorectal CancerPancreatic CancerAdvanced Solid TumorGynecologic CancerBreast CancerLung AdenocarcinomaHead and Neck Cancer
- Interventions
- Drug: PY159 Single agent dose level 4Drug: PY159 Single agent dose level 7Drug: PY159 Single agent dose level 2Drug: PY159 Single agent dose level 3Drug: PY159/Pembrolizumab Combination dose expansion cohort 6Drug: PY159 Single agent dose level 1Drug: PY159 Single agent dose expansion cohortDrug: PY159/Pembrolizumab Combination dose expansion cohort 2Drug: PY159/Pembrolizumab Combination dose expansion cohort 3Drug: PY159 Single agent dose level 5Drug: PY159 Single agent dose level 6Drug: PY159/Pembrolizumab Combination dose level 3Drug: PY159/Pembrolizumab Combination dose level 4Drug: PY159/Pembrolizumab Combination dose expansion cohort 1Drug: PY159/Pembrolizumab Combination dose expansion cohort 4Drug: PY159/Pembrolizumab Combination dose expansion cohort 5Drug: PY159/Pembrolizumab Combination dose level 1Drug: PY159/Pembrolizumab Combination dose level 2
- Registration Number
- NCT04682431
- Lead Sponsor
- Ikena Oncology
- Brief Summary
This is an open-label, multicenter, First-In-Human (FIH), Phase 1a/1b study of PY159 in subjects with locally advanced (unresectable) and/or metastatic solid tumors that are refractory or relapsed to Standard Of Care (including Checkpoint Inhibitors, if approved for that indication).
- Detailed Description
Part A: Dose escalation of PY159 alone and in combination with pembrolizumab in a standard 3+3 design Part B: Dose expansion of one or more dose levels of PY159 administered alone and in combination with pembrolizumab for predefined tumor histology
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 127
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: PY159 single agent dose level 4 PY159 Single agent dose level 4 PY159 dose level 4 Part A: PY159 single agent dose level 7 PY159 Single agent dose level 7 PY159 dose level 7 Part A: PY159 Single agent dose level 2 PY159 Single agent dose level 2 PY159 dose level 2 Part A: PY159 single agent dose level 3 PY159 Single agent dose level 3 PY159 dose level 3 PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 6 PY159/Pembrolizumab Combination dose expansion cohort 6 PY159 in combination with pembrolizumab dose expansion cohort 6 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression. Part A: PY159 Single agent dose level 1 PY159 Single agent dose level 1 PY159 dose level 1 IV administration, Q3 weekly until consent withdrawal, intolerable toxicity or investigator decision. PY159 Part B: Single agent dose expansion cohort(s) PY159 Single agent dose expansion cohort PY159 Single agent dose expansion cohort(s) PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 2 PY159/Pembrolizumab Combination dose expansion cohort 2 PY159 in combination with pembrolizumab dose expansion cohort 2 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression. PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 3 PY159/Pembrolizumab Combination dose expansion cohort 3 PY159 in combination with pembrolizumab dose expansion cohort 3 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression. Part A: PY159 single agent dose level 5 PY159 Single agent dose level 5 PY159 dose level 5 Part A: PY159 single agent dose level 6 PY159 Single agent dose level 6 PY159 dose level 6 Part A: PY159/Pembrolizumab Combination dose level 3 PY159/Pembrolizumab Combination dose level 3 PY159 dose level 3 in combination with pembrolizumab Part A: PY159/Pembrolizumab Combination dose level 4 PY159/Pembrolizumab Combination dose level 4 PY159 dose level 4 in combination with pembrolizumab PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 1 PY159/Pembrolizumab Combination dose expansion cohort 1 PY159 in combination with pembrolizumab dose expansion cohort 1 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression. PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 4 PY159/Pembrolizumab Combination dose expansion cohort 4 PY159 in combination with pembrolizumab dose expansion cohort 4 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression. PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 5 PY159/Pembrolizumab Combination dose expansion cohort 5 PY159 in combination with pembrolizumab dose expansion cohort 5 to further explore and characterize the anti-tumor activity of PY159 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM1 expression. Part A: PY159/Pembrolizumab Combination dose level 1 PY159/Pembrolizumab Combination dose level 1 PY159 dose level 1 in combination with pembrolizumab Part A: PY159/Pembrolizumab Combination dose level 2 PY159/Pembrolizumab Combination dose level 2 PY159 dose level 2 in combination with pembrolizumab
- Primary Outcome Measures
Name Time Method Dose Limiting Toxicity of PY159 (Part A only) 21 days Evaluation of dose-limiting toxicity (DLT).
Incidence of Adverse Events (AE) 36 months Adverse Events will be summarized by MedDRA system organ class and preferred term. Separate tabulations will be produced for all treatment emergent AEs, treatment related AEs, Serious Adverse Events (SAEs), discontinuations due to AEs, and AEs of at least NCI CTCAE grade 3 severity.
- Secondary Outcome Measures
Name Time Method Measure PY159 concentration at the end of infusion (CEOI) 36 months Measure PY159 concentration at the end of infusion (CEOI) after the first dose.
Measure PY159 maximum concentration (Cmax) 36 months Measure PY159 maximum concentration (Cmax) at various time points during Cycle 1. All subjects who received at least 1 dose of PY159 and have at least 1 measured concentration at a scheduled pharmacokinetics (PK) time point after start of dosing.
Measure PY159 concentration at the trough level (Ctrough) 36 months Measure PY159 concentration at the trough level (Ctrough). All subjects who received at least 1 dose of PY159 and have at least 1 measured concentration at a scheduled PK time point after start of dosing.
Measure PY159 Clearance (CL) 36 months Measure PY159 Clearance (CL). All subjects who received at least 1 dose of PY159 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.
Measure PY159 Volume at Steady State (Vss) 36 months Measure PY159 Volume at Steady State (Vss). All subjects who received at least 1 dose of PY159 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.
Measure PY159 Area under the curve (AUC)0-t 36 months Measure PY159 Area under the curve (AUC)0-t. All subjects who received at least 1 dose of PY159 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.
Measure PY159 half-life (T1/2) 36 months Measure PY159 half-life (T1/2). All subjects who received at least 1 dose of PY159 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.
Incidence of Anti-Drug Antibody (ADA) formation to PY159 36 months To evaluate the incidence of anti-drug antibody (ADA) formation to PY159
Determining PY159 time to maximum concentration (Tmax) 36 months Determining PY159 time to maximum concentration (Tmax) during Cycle 1.
Objective response rate (ORR) 36 months The incidents of ORR is defined as either a complete or partial response (PR) per RECIST. Subjects with no baseline data will be considered no responders. ORR will be summarized by dose, tumor type, and overall. ORR will be summarized descriptively.
Clinical Benefit Rate (CBR) 36 months Defined as the percentage of subjects who have achieved complete response (CR), partial response (PR) and stable disease (SD).
Duration of response (DOR) 36 months DOR will be calculated to determine durability. DOR will be measured from the time by which the criteria for CR or PR-whichever is recorded first-are met until the first date by which recurrent or progressive disease is objectively documented. DOR will be assessed using KAPLAN-MEIER methods.
Trial Locations
- Locations (17)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
USC Norris Cancer Center
🇺🇸Los Angeles, California, United States
UCLA Parkside Cancer Center
🇺🇸Santa Monica, California, United States
Florida Cancer Specialists - Sarasota - SCRI
🇺🇸Sarasota, Florida, United States
Smilow Cancer Hospital at Yale New Haven
🇺🇸New Haven, Connecticut, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
UCSF Mount Zion Cancer Center
🇺🇸San Francisco, California, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Mary Crowley Cancer Center
🇺🇸Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Start South Texas Accelerated Research Therapeutic
🇺🇸San Antonio, Texas, United States
The University of Oklahoma
🇺🇸Norman, Oklahoma, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States