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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).
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: PY159 Single agent dose level 1 | Experimental | PY159 dose level 1 IV administration, Q3 weekly until consent withdrawal, intolerable toxicity or investigator decision. |
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| Part A: PY159 Single agent dose level 2 | Experimental | PY159 dose level 2 |
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| Part A: PY159 single agent dose level 3 | Experimental | PY159 dose level 3 |
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| Part A: PY159 single agent dose level 4 | Experimental | PY159 dose level 4 |
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| Part A: PY159 single agent dose level 5 | Experimental | PY159 dose level 5 |
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| Part A: PY159 single agent dose level 6 | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PY159 Single agent dose level 1 | Drug | Dose of PY159 as a single agent given in a standard 3+3 design. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Measure PY159 concentration at the end of infusion (CEOI) | Measure PY159 concentration at the end of infusion (CEOI) after the first dose. | 36 months |
| Measure PY159 maximum concentration (Cmax) |
| Measure | Description | Time Frame |
|---|---|---|
| Progress free survival (PFS) | PFS will be measure from entry onto the study until disease progression or death from any cause. PFS will be assessed using KAPLAN-MEIER methods. | 36 months |
| Overall survival (OS) |
KEY ELIGIBILITY CRITERIA Inclusion Criteria
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:
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.
Exclusion Criteria
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Len Reyno, MD | Ikena Oncology | Study Director |
| Marc Chamberlain, MD | Ikena Oncology | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| USC Norris Cancer Center | Los Angeles | California | 90089 | United States | ||
| UCSF Mount Zion Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38809056 | Derived | 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. |
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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
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PY159 dose level 6
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| Part A: PY159 single agent dose level 7 | Experimental | PY159 dose level 7 |
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| Part A: PY159/Pembrolizumab Combination dose level 1 | Experimental | PY159 dose level 1 in combination with pembrolizumab |
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| Part A: PY159/Pembrolizumab Combination dose level 2 | Experimental | PY159 dose level 2 in combination with pembrolizumab |
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| Part A: PY159/Pembrolizumab Combination dose level 3 | Experimental | PY159 dose level 3 in combination with pembrolizumab |
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| Part A: PY159/Pembrolizumab Combination dose level 4 | Experimental | PY159 dose level 4 in combination with pembrolizumab |
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| PY159 Part B: Single agent dose expansion cohort(s) | Experimental | PY159 Single agent dose expansion cohort(s) |
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| PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 1 | Experimental | 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. |
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| PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 2 | Experimental | 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. |
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| PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 3 | Experimental | 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. |
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| PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 4 | Experimental | 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. |
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| PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 5 | Experimental | 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. |
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| PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 6 | Experimental | 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. |
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| PY159 Single agent dose level 2 | Drug | Dose of PY159 as a single agent given in a standard 3+3 design. |
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| PY159 Single agent dose level 3 | Drug | Dose of PY159 as a single agent given in a standard 3+3 design. |
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| PY159 Single agent dose level 4 | Drug | Dose of PY159 as a single agent given in a standard 3+3 design. |
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| PY159 Single agent dose level 5 | Drug | Dose of PY159 as a single agent given in a standard 3+3 design. |
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| PY159 Single agent dose level 6 | Drug | Dose of PY159 as a single agent given in a standard 3+3 design. |
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| PY159 Single agent dose level 7 | Drug | Dose of PY159 as a single agent given in a standard 3+3 design. |
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| PY159/Pembrolizumab Combination dose level 1 | Drug | Dose of PY159 and given in combination with pembrolizumab |
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| PY159/Pembrolizumab Combination dose level 2 | Drug | Dose of PY159 and given in combination with pembrolizumab |
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| PY159/Pembrolizumab Combination dose level 3 | Drug | Dose of PY159 and given in combination with pembrolizumab |
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| PY159/Pembrolizumab Combination dose level 4 | Drug | Dose of PY159 and given in combination with pembrolizumab |
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| PY159 Single agent dose expansion cohort | Drug | Dose of PY159 as a single agent given for predefined tumor histology |
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| PY159/Pembrolizumab Combination dose expansion cohort 1 | Drug | Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology |
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| PY159/Pembrolizumab Combination dose expansion cohort 2 | Drug | Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology |
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| PY159/Pembrolizumab Combination dose expansion cohort 3 | Drug | Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology |
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| PY159/Pembrolizumab Combination dose expansion cohort 4 | Drug | Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology |
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| PY159/Pembrolizumab Combination dose expansion cohort 5 | Drug | Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology |
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| PY159/Pembrolizumab Combination dose expansion cohort 6 | Drug | Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology |
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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.
| 36 months |
| Measure PY159 concentration at the trough level (Ctrough) | 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. | 36 months |
| Measure PY159 Area under the curve (AUC)0-t | 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. | 36 months |
| Measure PY159 half-life (T1/2) | 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. | 36 months |
| Measure PY159 Clearance (CL) | 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. | 36 months |
| Measure PY159 Volume at Steady State (Vss) | 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. | 36 months |
| Incidence of Anti-Drug Antibody (ADA) formation to PY159 | To evaluate the incidence of anti-drug antibody (ADA) formation to PY159 | 36 months |
| Determining PY159 time to maximum concentration (Tmax) | Determining PY159 time to maximum concentration (Tmax) during Cycle 1. | 36 months |
| Objective response rate (ORR) | 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. | 36 months |
| Clinical Benefit Rate (CBR) | Defined as the percentage of subjects who have achieved complete response (CR), partial response (PR) and stable disease (SD). | 36 months |
| Duration of response (DOR) | 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. | 36 months |
The duration of overall survival (OS) will be measured from the time of first study drug administration until the date of death. OS will be assessed using KAPLAN-MEIER methods.
| 36 months |
| 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 |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D015179 | Colorectal Neoplasms |
| D000077192 | Adenocarcinoma of Lung |
| D010190 | Pancreatic Neoplasms |
| D006258 | Head and Neck Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
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