A Study of PY314 in Subjects With Advanced Solid Tumors

NCT04691375 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: PY314-1-01
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 23

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).

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

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

• (Part A only) Dose Limiting Toxicity of PY314

  Evaluation of dose-limiting toxicity (DLT).

  Assessed during first 21 days of treatment

Secondary Outcomes (12)

• Measure PY314 concentration at the end of infusion (CEOI)

  36 months

• Measure PY314 concentration at the trough level (Ctrough)

  36 months

• Determining PY314 time to maximum concentration (Tmax)

  36 months

• Measure PY314 Area under the curve (AUC)0-t

  36 months

• Measure PY314 half-life (T1/2)

  36 months

Other Outcomes (2)

• Progress free survival (PFS)

  36 months

• Overall survival (OS)

  36 months

Study Arms (14)

Part A: PY314 Single agent dose level 1

EXPERIMENTAL

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.

Drug: PY314

Part A: PY314 Single agent dose level 2

EXPERIMENTAL

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.

Drug: PY314

Part A: PY314 Single agent dose level 3

EXPERIMENTAL

PY314 single agent dose level 3 to identify the maximum tolerated dose and/or to determine the recommended dose for expansion of PY314

Drug: PY314

Part A: PY314 Single agent dose level 4

EXPERIMENTAL

PY314 single agent dose level 4 to characterize the pharmacokinetic profile of PY314 as a single agent.

Drug: PY314

Part A: Combination dose level 1

EXPERIMENTAL

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.

Drug: Combination Therapy: PY314 + Pembrolizumab

Part A: Combination dose level 2

EXPERIMENTAL

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.

Drug: Combination Therapy: PY314 + Pembrolizumab

Part A: Combination dose level 3

EXPERIMENTAL

PY314 combination dose level 3 to characterize the pharmacokinetic profile of PY314 as a single agent and in combination with pembrolizumab.

Drug: Combination Therapy: PY314 + Pembrolizumab

Part A: Combination dose level 4

EXPERIMENTAL

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.

Drug: Combination Therapy: PY314 + Pembrolizumab

Part B: Single agent dose expansion dose level 1

EXPERIMENTAL

PY314 single agent dose expansion dose level 1 to define further the safety and tolerability of PY314 alone.

Drug: PY314

Part B: Combination dose expansion cohort 1

EXPERIMENTAL

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.

Drug: Combination Therapy: PY314 + Pembrolizumab

Part B: Combination dose expansion cohort 2

EXPERIMENTAL

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.

Drug: Combination Therapy: PY314 + Pembrolizumab

Part B: Combination dose expansion cohort 3

EXPERIMENTAL

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.

Drug: Combination Therapy: PY314 + Pembrolizumab

Part B: Combination dose expansion cohort 4

EXPERIMENTAL

PY314 in combination with pembrolizumab dose expansion cohort 4 to evaluate the incidence of ADA formation and TREM2 expression.

Drug: Combination Therapy: PY314 + Pembrolizumab

Part B: Combination dose expansion cohort 5

EXPERIMENTAL

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.

Drug: Combination Therapy: PY314 + Pembrolizumab

Interventions

PY314 DRUG

Dose of PY314 as a single agent given in a standard 3+3 design.

Part A: PY314 Single agent dose level 1; Part A: PY314 Single agent dose level 2; Part A: PY314 Single agent dose level 3; Part A: PY314 Single agent dose level 4; Part B: Single agent dose expansion dose level 1

Combination Therapy: PY314 + Pembrolizumab DRUG

Dose of PY314 alone and given in combination with pembrolizumab

Also known as: PY314, Pembrolizumab

Part A: Combination dose level 1; Part A: Combination dose level 2; Part A: Combination dose level 3; Part A: Combination dose level 4; Part B: Combination dose expansion cohort 1; Part B: Combination dose expansion cohort 2; Part B: Combination dose expansion cohort 3; Part B: Combination dose expansion cohort 4; Part B: Combination dose expansion cohort 5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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 (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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ikena Oncology: lead

Study Sites (23)

Mayo Clinic Scottsdale - PPDS

Phoenix, Arizona, 85054, United States

Location

Honor Health Research Institute

Scottsdale, Arizona, 85258-4566, United States

Location

City of Hope - Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Stanford Hospital and Clinics

Palo Alto, California, 94304, United States

Location

UC San Diego Moores Cancer Center

San Diego, California, 92093, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Mayo Clinic Jacksonville - PPDS

Jacksonville, Florida, 32224, United States

Location

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic - PPDS

Rochester, Minnesota, 55905, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Oklahoma Peggy and Charles Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

OHSU Knight Cancer Institute Beaverton Clinic

Portland, Oregon, 97239, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Start South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

Wisconsin Institutes for Medical Research

Madison, Wisconsin, 53705, United States

Location

Related Publications (2)

• Beckermann KE, Patnaik A, Winer I, Tan W, Bashir B, Kyriakopoulos CE, Sweis RF, Chamberlain M, Rini BI. A phase 1b open-label study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of py314 in combination with pembrolizumab in patients with advanced renal cell carcinoma. Invest New Drugs. 2024 Apr;42(2):179-184. doi: 10.1007/s10637-024-01419-1. Epub 2024 Feb 19.

  PMID: 38372949 DERIVED

• 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.

  PMID: 34686340 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Colorectal Neoplasms; Adenocarcinoma of Lung; Carcinoma, Renal Cell; Triple Negative Breast Neoplasms; Ovarian Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Len Reyno, MD

  Ikena Oncology

  STUDY DIRECTOR

• Marc Chamberlain, MD

  Ikena Oncology

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: December 8, 2020
• First Posted: December 31, 2020
• Study Start: October 29, 2020
• Primary Completion: August 31, 2023
• Study Completion: September 22, 2023
• Last Updated: March 22, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (23)