Clinical trial NCT04691375: A Study of PY314 in Subjects With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: Ikena Oncology
Sponsor class: INDUSTRY
First posted: 2020-12-31
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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

Eligibility criteria: 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 (Gynecological cancers \[including ovarian, fallopian, primary peritoneal, endometrial, cervical, vaginal, vulvar\], gastric \[adenocarcinoma\], Colorectal (\[MSIlow and CPI refractory MSIhigh\]), lung \[non-small cell lung adenocarcinoma and squamous cell carcinoma\] 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, renal \[clear cell and non-clear cell\], breast \[TNBC and HR+ HER-2-\] with locally advanced or 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).
  * Expansion Cohorts (Part B): Subjects with advanced solid tumors selected from 5 prespecified cancers based on preclinical and Part A.
* Subjects must provide an original, diagnostic tumor sample to determine TREM2 expression (sites have verified source prior to screening and availability of archival tissue during screening). Subjects without an archival tissue sample will only be eligible if they choose and consent to provide a CNB of primary or a metastatic lesion required for part B, used in Part A only if an archival specimen unavailable.
* Subjects must have documented disease progression (including 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 (including Grade \< 2 alopecia or peripheral neuropathy, or if controlled on thyroid replacement therapy).
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
* Coagulation: International Normalized Ratio (INR) ≤ 1.3, unless on a therapeutic anticoagulant
* Adequate hematologic function defined as follows: Platelets ≥ 100 x 10\^9/L; Hemoglobin ≥ 8.0 g/dL; ANC ≥ 1.5 x 10\^9/L (without granulocytic growth factors within the previous 7 days of obtaining the screening hematologic laboratory values)
* Adequate hepatic function defined as follows: AST / ALT ≤ 2.5 x upper limit of normal (ULN) (if liver metastases are present, ≤ 5 x ULN); Total or conjugated bilirubin ≤ 1.5 x ULN
* Adequate renal function defined as follows: Serum Creatinine ≤ 2 x ULN or creatinine clearance (CrCl) ≥45 mL/min as calculated by the Cockroft-Gault method

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.

Primary outcomes:
measure: Incidence of Adverse Events (AE)
timeFrame: 36 months
measure: (Part A only) Dose Limiting Toxicity of PY314
timeFrame: Assessed during first 21 days of treatment
Secondary outcomes:
measure: Measure PY314 concentration at the end of infusion (CEOI)
timeFrame: 36 months
measure: Measure PY314 concentration at the trough level (Ctrough)
timeFrame: 36 months
measure: Determining PY314 time to maximum concentration (Tmax)
timeFrame: 36 months
measure: Measure PY314 Area under the curve (AUC)0-t
timeFrame: 36 months
measure: Measure PY314 half-life (T1/2)
timeFrame: 36 months
measure: Measure PY314 Clearance (CL)
timeFrame: 36 months
measure: Measure PY314 Volume at Steady State (Vss)
timeFrame: 36 months
measure: Measure PY314 maximum concentration (Cmax)
timeFrame: 36 months
measure: Incidence of Anti-Drug Antibody (ADA) formation to PY314
timeFrame: 36 months
measure: Objective response rate (ORR)
timeFrame: 36 months
measure: Clinical Benefit Rate (CBR)
timeFrame: 36 Months
measure: Duration of response (DOR)
timeFrame: 36 months
Other outcomes:
measure: Progress free survival (PFS)
timeFrame: 36 months
measure: Overall survival (OS)
timeFrame: 36 months
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Scottsdale - PPDS
state: Arizona
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Duarte
country: United States
facility: City of Hope - Comprehensive Cancer Center
state: California
city: Palo Alto
country: United States
facility: Stanford Hospital and Clinics
state: California
city: San Diego
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville - PPDS
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - PPDS
state: Minnesota
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Peggy and Charles Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: OHSU Knight Cancer Institute Beaverton Clinic
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: San Antonio
country: United States
facility: Start South Texas Accelerated Research Therapeutics
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Madison
country: United States
facility: Wisconsin Institutes for Medical Research
state: Wisconsin
Study officials:
affiliation: Ikena Oncology
name: Len Reyno, MD
role: STUDY_DIRECTOR
affiliation: Ikena Oncology
name: Marc Chamberlain, MD
role: STUDY_DIRECTOR
References:
citation: 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.