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A Phase 1a/1b FIH Study of PY159 and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
A Phase 1a/1b Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PY159 as a Single Agent and In Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
1 other identifier
interventional
127
1 country
17
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2020
Typical duration for phase_1
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 10, 2020
CompletedFirst Submitted
Initial submission to the registry
December 11, 2020
CompletedFirst Posted
Study publicly available on registry
December 23, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 25, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
August 31, 2023
CompletedMarch 22, 2024
March 1, 2024
2.8 years
December 11, 2020
March 20, 2024
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of Adverse Events (AE)
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.
36 months
Dose Limiting Toxicity of PY159 (Part A only)
Evaluation of dose-limiting toxicity (DLT).
21 days
Secondary Outcomes (12)
Measure PY159 concentration at the end of infusion (CEOI)
36 months
Measure PY159 maximum concentration (Cmax)
36 months
Measure PY159 concentration at the trough level (Ctrough)
36 months
Measure PY159 Area under the curve (AUC)0-t
36 months
Measure PY159 half-life (T1/2)
36 months
- +7 more secondary outcomes
Other Outcomes (2)
Progress free survival (PFS)
36 months
Overall survival (OS)
36 months
Study Arms (18)
Part A: PY159 Single agent dose level 1
EXPERIMENTALPY159 dose level 1 IV administration, Q3 weekly until consent withdrawal, intolerable toxicity or investigator decision.
Part A: PY159 Single agent dose level 2
EXPERIMENTALPY159 dose level 2
Part A: PY159 single agent dose level 3
EXPERIMENTALPY159 dose level 3
Part A: PY159 single agent dose level 4
EXPERIMENTALPY159 dose level 4
Part A: PY159 single agent dose level 5
EXPERIMENTALPY159 dose level 5
Part A: PY159 single agent dose level 6
EXPERIMENTALPY159 dose level 6
Part A: PY159 single agent dose level 7
EXPERIMENTALPY159 dose level 7
Part A: PY159/Pembrolizumab Combination dose level 1
EXPERIMENTALPY159 dose level 1 in combination with pembrolizumab
Part A: PY159/Pembrolizumab Combination dose level 2
EXPERIMENTALPY159 dose level 2 in combination with pembrolizumab
Part A: PY159/Pembrolizumab Combination dose level 3
EXPERIMENTALPY159 dose level 3 in combination with pembrolizumab
Part A: PY159/Pembrolizumab Combination dose level 4
EXPERIMENTALPY159 dose level 4 in combination with pembrolizumab
PY159 Part B: Single agent dose expansion cohort(s)
EXPERIMENTALPY159 Single agent dose expansion cohort(s)
PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 1
EXPERIMENTALPY159 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 2
EXPERIMENTALPY159 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
EXPERIMENTALPY159 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.
PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 4
EXPERIMENTALPY159 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
EXPERIMENTALPY159 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.
PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 6
EXPERIMENTALPY159 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.
Interventions
Dose of PY159 as a single agent given in a standard 3+3 design.
Dose of PY159 as a single agent given in a standard 3+3 design.
Dose of PY159 as a single agent given in a standard 3+3 design.
Dose of PY159 as a single agent given in a standard 3+3 design.
Dose of PY159 as a single agent given in a standard 3+3 design.
Dose of PY159 as a single agent given in a standard 3+3 design.
Dose of PY159 as a single agent given in a standard 3+3 design.
Dose of PY159 and given in combination with pembrolizumab
Dose of PY159 and given in combination with pembrolizumab
Dose of PY159 and given in combination with pembrolizumab
Dose of PY159 and given in combination with pembrolizumab
Dose of PY159 as a single agent given for predefined tumor histology
Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology
Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology
Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology
Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology
Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology
Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology
Eligibility Criteria
You may qualify if:
- Adults ≥18 years of age at the time of study consent
- Subjects with any of the following eligible solid tumor diagnoses as confirmed by cytology or histology. Escalation Cohorts (Part A): Subjects with advanced solid tumors from pre-specified tumor types:
- head and neck \[squamous cell carcinoma, salivary gland, thyroid\],
- gynecologic \[including ovarian, fallopian, primary peritoneal, endometrial, cervical, uterine, vaginal, vulvar\],
- pancreatic \[adenocarcinoma\],
- lung \[adenocarcinoma and squamous cell carcinoma\] who are recurrent or refractory to platinum-based chemotherapy in addition to prior treatment with CPI Programmed Cell Death-1 (PD-1)/Programmed Cell Death-Ligand 1 (PD-L1) or who give informed consent to forego such therapy,
- gastric and esophagogastric junction adenocarcinomas \[MSI low and CPI refractory MSI high\],
- breast \[TNBC and HR+, HER2-\] with metastatic disease that is relapsed or refractory to at least one line of post adjuvant therapy (including a CPI-either alone or in combination, if approved for that indication, and not eligible for other targeted therapies specific for their tumor type).
- Subjects must provide an original, diagnostic tumor sample to determine TREM1 expression (sites have verified source prior to screening and availability of archival tissue during screening). For Part A subjects without an archival tissue sample will only be eligible if they choose and consent to provide a CNB of a primary or metastatic lesion.
- Subjects must have documented radiographic disease progression that include prior treatment with a CPI (alone or in combination), if approved for that indication.
- There is no limit to the number of prior treatments
- Measurable disease by RECIST 1.1.
- All acute toxic effects of any prior antitumor therapy, including immunotherapy, have resolved to Grade \< 2 before the start of study drug dosing (except for alopecia or peripheral neuropathy which may be Grade \<2 or medication controlled thyroid replacement therapy).
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2.
You may not qualify if:
- Subject is a candidate for approved molecularly targeted therapy (e.g., drugs targeting EGFR,VEGF, ALK, ROS-1, NTRK, MET, RET, and BRAF V600E, HER2). Applies to enrolled subjects on both Part A and Part B of the study.
- History of autoimmune disorder requiring ongoing or intermittent disease-modifying therapy excluding thyroid disease well controlled on replacement therapy.
- Untreated and/or uncontrolled brain metastases Stable treated or asymptomatic brain metastases (for at least 1 month prior to enrollment may be enrolled. Subjects with stable treated or asymptomatic brain metastases receiving glucocorticoids must be on a stable dose \[≤ 2 mg/day of dexamethasone or an equivalent glucocorticoid\] for a minimum of 1month prior to enrollment.)
- Uncontrolled intercurrent illness including, but not limited to, active SARS-CoV-2 infection, active or chronic bleeding event within 28 days prior to first dose of study drug or psychiatric illness/social situation that would limit compliance with study requirements as judged by treating physician.
- Decompensated liver disease as evidenced by hepatic encephalopathy or coagulopathy.
- Active angina or Class III or IV Congestive Heart Failure (CHF) (NYHA CHF Functional Classification System) or clinically significant cardiac disease within 12 months of first dose. of study drug, including MI, unstable angina, Grade 2 or greater peripheral vascular disease, uncontrolled HTN, or arrhythmias not controlled by medication.
- Any anti-cancer therapy, including small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy (with the exception of bone-modifying agents as supportive care), radiotherapy or any other agents to treat cancer within 14-21 days (dependent upon the agent and drug half-life) of first dose of study drug. Subjects with a prior history of prostate cancer on LHRH agonist are eligible provided they have no evidence of metastatic disease.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Ikena Oncologylead
Study Sites (17)
USC Norris Cancer Center
Los Angeles, California, 90089, United States
UCSF Mount Zion Cancer Center
San Francisco, California, 94115, United States
UCLA Parkside Cancer Center
Santa Monica, California, 90404, United States
University of Colorado
Aurora, Colorado, 80045, United States
Smilow Cancer Hospital at Yale New Haven
New Haven, Connecticut, 06511, United States
Florida Cancer Specialists - Sarasota - SCRI
Sarasota, Florida, 34232, United States
Indiana University
Indianapolis, Indiana, 46202-5116, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
The University of Oklahoma
Norman, Oklahoma, 73019, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Mary Crowley Cancer Center
Dallas, Texas, 75230, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Start South Texas Accelerated Research Therapeutic
San Antonio, Texas, 78229, United States
Related Publications (1)
Fan Y, Xu Y, Huo Z, Zhang H, Peng L, Jiang X, Thomson AW, Dai H. Role of triggering receptor expressed on myeloid cells-1 in kidney diseases: A biomarker and potential therapeutic target. Chin Med J (Engl). 2024 Jul 20;137(14):1663-1673. doi: 10.1097/CM9.0000000000003197. Epub 2024 May 28.
PMID: 38809056DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Len Reyno, MD
Ikena Oncology
- STUDY DIRECTOR
Marc Chamberlain, MD
Ikena Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 11, 2020
First Posted
December 23, 2020
Study Start
November 10, 2020
Primary Completion
August 25, 2023
Study Completion
August 31, 2023
Last Updated
March 22, 2024
Record last verified: 2024-03
Data Sharing
- IPD Sharing
- Will not share