December 8, 2020
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December 31, 2020
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March 22, 2024
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October 29, 2020
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August 31, 2023 (Final data collection date for primary outcome measure)
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- Incidence of Adverse Events (AE) [ Time Frame: 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.
- (Part A only) Dose Limiting Toxicity of PY314 [ Time Frame: Assessed during first 21 days of treatment ]
Evaluation of dose-limiting toxicity (DLT).
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- Incidence of Adverse Events (AE) [ Time Frame: 12 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.
- Measure PY314 concentration at the end of infusion (CEOI) [ Time Frame: 12 months ]
Measure PY314 concentration at the end of infusion (CEOI) after the first dose.
- Measure PY314 maximum concentration (Cmax) [ Time Frame: 12 months ]
Measure PY314 maximum concentration (Cmax) at various time points during Cycle 1. All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing.
- Measure PY314 concentration at the trough level (Ctrough) [ Time Frame: 12 months ]
Measure PY314 concentration at the trough level (Ctrough). All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing.
- Determining PY314 time to maximum concentration (Tmax) [ Time Frame: 12 months ]
Determining PY314 time to maximum concentration (Tmax) during Cycle 1.
- Measure PY314 Area under the curve (AUC)0-t [ Time Frame: 12 months ]
Measure PY314 Area under the curve (AUC)0-t. All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.
- Measure PY314 half-life (T1/2) [ Time Frame: 12 months ]
Measure PY314 half-life (T1/2). All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.
- Measure PY314 Clearance (CL) [ Time Frame: 12 months ]
Measure PY314 Clearance (CL). All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.
- Measure PY314 Volume at Steady State (Vss) [ Time Frame: 12 months ]
Measure PY314 Volume at Steady State (Vss). All subjects who received at least 1 dose of PY314 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 PY314 [ Time Frame: 12 months ]
To evaluate the incidence of anti-drug antibody (ADA) formation to PY314
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- Measure PY314 concentration at the end of infusion (CEOI) [ Time Frame: 36 months ]
Measure PY314 concentration at the end of infusion (CEOI) after the first dose.
- Measure PY314 concentration at the trough level (Ctrough) [ Time Frame: 36 months ]
Measure PY314 concentration at the trough level (Ctrough). All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing.
- Determining PY314 time to maximum concentration (Tmax) [ Time Frame: 36 months ]
Determining PY314 time to maximum concentration (Tmax) during Cycle 1.
- Measure PY314 Area under the curve (AUC)0-t [ Time Frame: 36 months ]
Measure PY314 Area under the curve (AUC)0-t. All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.
- Measure PY314 half-life (T1/2) [ Time Frame: 36 months ]
Measure PY314 half-life (T1/2). All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.
- Measure PY314 Clearance (CL) [ Time Frame: 36 months ]
Measure PY314 Clearance (CL). All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.
- Measure PY314 Volume at Steady State (Vss) [ Time Frame: 36 months ]
Measure PY314 Volume at Steady State (Vss). All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing for at least 1 PK analyte.
- Measure PY314 maximum concentration (Cmax) [ Time Frame: 36 months ]
Measure PY314 maximum concentration (Cmax) at various time points during Cycle 1. All subjects who received at least 1 dose of PY314 and have at least 1 measured concentration at a scheduled PK time point after start of dosing.
- Incidence of Anti-Drug Antibody (ADA) formation to PY314 [ Time Frame: 36 months ]
To evaluate the incidence of anti-drug antibody (ADA) formation to PY314
- Objective response rate (ORR) [ Time Frame: 36 months ]
The incidents of ORR is defined as either a complete or partial response 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) [ Time Frame: 36 Months ]
Defined as the percentage of subjects who have achieved complete response, partial response and stable disease.
- Duration of response (DOR) [ Time Frame: 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.
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- Objective response rate (ORR) [ Time Frame: 36 months ]
The incidents of ORR is defined as either a complete or partial response 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.
- Deceased control rate (DCR) [ Time Frame: 36 months ]
DCR will be measure per resists 1.1 criteria. DCR will be summarized descriptively.
- Duration of response (DOR) [ Time Frame: 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.
- Progress free survival (PFS) [ Time Frame: 36 months ]
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.
- Overall survival (OS) [ Time Frame: 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.
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- Progress free survival (PFS) [ Time Frame: 36 months ]
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.
- Overall survival (OS) [ Time Frame: 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.
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Not Provided
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A Study of PY314 in Subjects With Advanced Solid Tumors
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A Phase 1a/1b Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PY314 as a Single Agent and In Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
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This is an open-label, multicenter, first in human, Phase 1a/1b study of PY314 in subjects with locally advanced (unresectable) and/or metastatic solid tumors that are refractory or relapsed to standard of care (including pembrolizumab, if approved for that indication).
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Part A: Dose escalation of PY314 alone and in combination with pembrolizumab in a standard 3+3 design Part B: Dose expansion of one or more dose levels of PY314 administered alone and in combination with pembrolizumab for predefined tumor histology
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Interventional
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Phase 1
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Allocation: Non-Randomized Intervention Model: Sequential Assignment Intervention Model Description: Part A: Dose escalation of PY314 alone and in combination with pembrolizumab in a standard 3+3 design
Part B: Dose expansion of one or more dose levels of PY314 administered alone and in combination with pembrolizumab for predefined tumor histology Masking: None (Open Label) Primary Purpose: Treatment
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- Advanced Solid Tumor
- Gynecologic Cancer
- Breast Cancer
- Colorectal Cancer
- Lung Adenocarcinoma
- Renal Cell Carcinoma
- Triple Negative Breast Cancer
- Hormone Receptor/Growth Factor Receptor-Negative Breast Cancer
- Ovarian Cancer
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- Experimental: Part A: PY314 Single agent dose level 1
PY314 single agent dose level will depend on any safety signal observed in this cohorts only. Following the determination of the safety and tolerability of at least two PY314 dose levels by the safety review committee.
Intervention: Drug: PY314
- Experimental: Part A: PY314 Single agent dose level 2
PY314 single agent dose level 2 dose escalation of PY314 as a single agent will continue in the absence of unacceptable dose limiting toxicity to the maximum administered dose as defined in the predefined dose escalation schema.
Intervention: Drug: PY314
- Experimental: Part A: PY314 Single agent dose level 3
PY314 single agent dose level 3 to identify the maximum tolerated dose and/or to determine the recommended dose for expansion of PY314
Intervention: Drug: PY314
- Experimental: Part A: PY314 Single agent dose level 4
PY314 single agent dose level 4 to characterize the pharmacokinetic profile of PY314 as a single agent.
Intervention: Drug: PY314
- Experimental: Part A: Combination dose level 1
Combination dose level 1 to characterize the safety and tolerability of PY314 as a single agent and in combination with pembrolizumab in subjects with advanced refractory solid tumors including refractory to check point inhibitor.
Intervention: Drug: Combination Therapy: PY314 + Pembrolizumab
- Experimental: Part A: Combination dose level 2
PY314 combination dose level 2 to identify the maximum tolerated dose and/or to determine the recommended dose for expansion of PY314 administered alone and in combination with pembrolizumab.
Intervention: Drug: Combination Therapy: PY314 + Pembrolizumab
- Experimental: Part A: Combination dose level 3
PY314 combination dose level 3 to characterize the pharmacokinetic profile of PY314 as a single agent and in combination with pembrolizumab.
Intervention: Drug: Combination Therapy: PY314 + Pembrolizumab
- Experimental: Part A: Combination dose level 4
PY314 combination dose level 4 to describe, in subjects selected by pre-specified tumor histology, anti-tumor activity of PY314 administered alone and in combination with pembrolizumab.
Intervention: Drug: Combination Therapy: PY314 + Pembrolizumab
- Experimental: Part B: Single agent dose expansion dose level 1
PY314 single agent dose expansion dose level 1 to define further the safety and tolerability of PY314 alone.
Intervention: Drug: PY314
- Experimental: Part B: Combination dose expansion cohort 1
PY314 in combination with pembrolizumab dose expansion cohort 1 to define the safety and tolerability of PY314 alone and in combination with pembrolizumab over multiple treatment cycles in subjects with pre-defined tumor histologies and confirmed TREM2 expression.
Intervention: Drug: Combination Therapy: PY314 + Pembrolizumab
- Experimental: Part B: Combination dose expansion cohort 2
PY314 in combination with pembrolizumab dose expansion cohort 2 to further characterize the PK profile of PY314 as a single agent and in combination with pembrolizumab.
Intervention: Drug: Combination Therapy: PY314 + Pembrolizumab
- Experimental: Part B: Combination dose expansion cohort 3
PY314 in combination with pembrolizumab dose expansion cohort 3 to characterize the anti-tumor activity of PY314 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM2 expression.
Intervention: Drug: Combination Therapy: PY314 + Pembrolizumab
- Experimental: Part B: Combination dose expansion cohort 4
PY314 in combination with pembrolizumab dose expansion cohort 4 to evaluate the incidence of ADA formation and TREM2 expression.
Intervention: Drug: Combination Therapy: PY314 + Pembrolizumab
- Experimental: Part B: Combination dose expansion cohort 5
PY314 in combination with pembrolizumab dose expansion cohort 5 to further explore and characterize the anti-tumor activity of PY314 alone and in combination with pembrolizumab in subjects with selected prespecified tumor histologies and known TREM2 expression.
Intervention: Drug: Combination Therapy: PY314 + Pembrolizumab
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Binnewies M, Pollack JL, Rudolph J, Dash S, Abushawish M, Lee T, Jahchan NS, Canaday P, Lu E, Norng M, Mankikar S, Liu VM, Du X, Chen A, Mehta R, Palmer R, Juric V, Liang L, Baker KP, Reyno L, Krummel MF, Streuli M, Sriram V. Targeting TREM2 on tumor-associated macrophages enhances immunotherapy. Cell Rep. 2021 Oct 19;37(3):109844. doi: 10.1016/j.celrep.2021.109844.
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Terminated
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86
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216
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September 22, 2023
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August 31, 2023 (Final data collection date for primary outcome measure)
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KEY ELIGIBILITY CRITERIA
Inclusion Criteria:
Exclusion Criteria:
- Subject is a candidate for 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 otherwise well controlled on replacement therapy
- Stable treated or asymptomatic brain metastases for at least 3 months documented by brain imaging 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 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, CHF, uncontrolled HTN, or arrhythmias not controlled by medication
- Any anti-cancer therapy, including small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy (except for bone-modifying agents as supportive care), radiotherapy, or any other agents to treat cancer within 21 days (dependent upon the agent and drug half-life), of first dose of study drug
- Refractory lung cancer subjects who have progressed within 3 months of initiating chemotherapy-doublet regimens or lung cancer subjects who have progressed within 6 months of initiation immunotherapy-chemotherapy combination treatment.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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United States
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NCT04691375
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PY314-1-01
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Ikena Oncology
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Same as current
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Ikena Oncology
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Same as current
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Not Provided
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Study Director: |
Len Reyno, MD |
Ikena Oncology |
Study Director: |
Marc Chamberlain, MD |
Ikena Oncology |
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Ikena Oncology
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March 2024
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