A Phase 1a/1b FIH Study of PY159 and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

NCT ID: NCT04682431

Last Updated: 2024-03-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-10
• Study Completion Date: 2023-08-31

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).

Detailed Description

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

Conditions

Advanced Solid Tumor; Gynecologic Cancer; Breast Cancer; Colorectal Cancer; Gastric Adenocarcinoma; Lung Adenocarcinoma; Pancreatic Cancer; Head and Neck Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: PY159 Single agent dose level 1

PY159 dose level 1 IV administration, Q3 weekly until consent withdrawal, intolerable toxicity or investigator decision.

Group Type: EXPERIMENTAL

PY159 Single agent dose level 1

Intervention Type: DRUG

Dose of PY159 as a single agent given in a standard 3+3 design.

Part A: PY159 Single agent dose level 2

PY159 dose level 2

Group Type: EXPERIMENTAL

PY159 Single agent dose level 2

Intervention Type: DRUG

Dose of PY159 as a single agent given in a standard 3+3 design.

Part A: PY159 single agent dose level 3

PY159 dose level 3

Group Type: EXPERIMENTAL

PY159 Single agent dose level 3

Intervention Type: DRUG

Dose of PY159 as a single agent given in a standard 3+3 design.

Part A: PY159 single agent dose level 4

PY159 dose level 4

Group Type: EXPERIMENTAL

PY159 Single agent dose level 4

Intervention Type: DRUG

Dose of PY159 as a single agent given in a standard 3+3 design.

Part A: PY159 single agent dose level 5

PY159 dose level 5

Group Type: EXPERIMENTAL

PY159 Single agent dose level 5

Intervention Type: DRUG

Dose of PY159 as a single agent given in a standard 3+3 design.

Part A: PY159 single agent dose level 6

PY159 dose level 6

Group Type: EXPERIMENTAL

PY159 Single agent dose level 6

Intervention Type: DRUG

Dose of PY159 as a single agent given in a standard 3+3 design.

Part A: PY159 single agent dose level 7

PY159 dose level 7

Group Type: EXPERIMENTAL

PY159 Single agent dose level 7

Intervention Type: DRUG

Dose of PY159 as a single agent given in a standard 3+3 design.

Part A: PY159/Pembrolizumab Combination dose level 1

PY159 dose level 1 in combination with pembrolizumab

Group Type: EXPERIMENTAL

PY159/Pembrolizumab Combination dose level 1

Intervention Type: DRUG

Dose of PY159 and given in combination with pembrolizumab

Part A: PY159/Pembrolizumab Combination dose level 2

PY159 dose level 2 in combination with pembrolizumab

Group Type: EXPERIMENTAL

PY159/Pembrolizumab Combination dose level 2

Intervention Type: DRUG

Dose of PY159 and given in combination with pembrolizumab

Part A: PY159/Pembrolizumab Combination dose level 3

PY159 dose level 3 in combination with pembrolizumab

Group Type: EXPERIMENTAL

PY159/Pembrolizumab Combination dose level 3

Intervention Type: DRUG

Dose of PY159 and given in combination with pembrolizumab

Part A: PY159/Pembrolizumab Combination dose level 4

PY159 dose level 4 in combination with pembrolizumab

Group Type: EXPERIMENTAL

PY159/Pembrolizumab Combination dose level 4

Intervention Type: DRUG

Dose of PY159 and given in combination with pembrolizumab

PY159 Part B: Single agent dose expansion cohort(s)

PY159 Single agent dose expansion cohort(s)

Group Type: EXPERIMENTAL

PY159 Single agent dose expansion cohort

Intervention Type: DRUG

Dose of PY159 as a single agent given for predefined tumor histology

PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 1

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.

Group Type: EXPERIMENTAL

PY159/Pembrolizumab Combination dose expansion cohort 1

Intervention Type: DRUG

Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology

PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 2

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.

Group Type: EXPERIMENTAL

PY159/Pembrolizumab Combination dose expansion cohort 2

Intervention Type: DRUG

Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology

PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 3

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.

Group Type: EXPERIMENTAL

PY159/Pembrolizumab Combination dose expansion cohort 3

Intervention Type: DRUG

Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology

PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 4

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.

Group Type: EXPERIMENTAL

PY159/Pembrolizumab Combination dose expansion cohort 4

Intervention Type: DRUG

Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology

PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 5

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.

Group Type: EXPERIMENTAL

PY159/Pembrolizumab Combination dose expansion cohort 5

Intervention Type: DRUG

Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology

PY159 Part B: PY159/Pembrolizumab Combination dose expansion cohort 6

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.

Group Type: EXPERIMENTAL

PY159/Pembrolizumab Combination dose expansion cohort 6

Intervention Type: DRUG

Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology

Interventions

PY159 Single agent dose level 1

Dose of PY159 as a single agent given in a standard 3+3 design.

Intervention Type: DRUG

PY159 Single agent dose level 2

Dose of PY159 as a single agent given in a standard 3+3 design.

Intervention Type: DRUG

PY159 Single agent dose level 3

Dose of PY159 as a single agent given in a standard 3+3 design.

Intervention Type: DRUG

PY159 Single agent dose level 4

Dose of PY159 as a single agent given in a standard 3+3 design.

Intervention Type: DRUG

PY159 Single agent dose level 5

Dose of PY159 as a single agent given in a standard 3+3 design.

Intervention Type: DRUG

PY159 Single agent dose level 6

Dose of PY159 as a single agent given in a standard 3+3 design.

Intervention Type: DRUG

PY159 Single agent dose level 7

Dose of PY159 as a single agent given in a standard 3+3 design.

Intervention Type: DRUG

PY159/Pembrolizumab Combination dose level 1

Dose of PY159 and given in combination with pembrolizumab

Intervention Type: DRUG

PY159/Pembrolizumab Combination dose level 2

Dose of PY159 and given in combination with pembrolizumab

Intervention Type: DRUG

PY159/Pembrolizumab Combination dose level 3

Dose of PY159 and given in combination with pembrolizumab

Intervention Type: DRUG

PY159/Pembrolizumab Combination dose level 4

Dose of PY159 and given in combination with pembrolizumab

Intervention Type: DRUG

PY159 Single agent dose expansion cohort

Dose of PY159 as a single agent given for predefined tumor histology

Intervention Type: DRUG

PY159/Pembrolizumab Combination dose expansion cohort 1

Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology

Intervention Type: DRUG

PY159/Pembrolizumab Combination dose expansion cohort 2

Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology

Intervention Type: DRUG

PY159/Pembrolizumab Combination dose expansion cohort 3

Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology

Intervention Type: DRUG

PY159/Pembrolizumab Combination dose expansion cohort 4

Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology

Intervention Type: DRUG

PY159/Pembrolizumab Combination dose expansion cohort 5

Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology

Intervention Type: DRUG

PY159/Pembrolizumab Combination dose expansion cohort 6

Dose of PY159 as a single agent and in combination with pembrolizumab for predefined tumor histology

Intervention Type: DRUG

Other Intervention Names

PY159; PY159; PY159; PY159; PY159; PY159; PY159; PY159; Pembrolizumab; PY159; Pembrolizumab; PY159; Pembrolizumab; PY159; Pembrolizumab; PY159; PY159; Pembrolizumab; PY159; Pembrolizumab; PY159; Pembrolizumab; PY159; Pembrolizumab; PY159; Pembrolizumab; PY159; Pembrolizumab

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:

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ikena Oncology

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Len Reyno, MD

Role: STUDY_DIRECTOR

Ikena Oncology

Marc Chamberlain, MD

Role: STUDY_DIRECTOR

Ikena Oncology

Locations

USC Norris Cancer Center

Los Angeles, California, United States

UCSF Mount Zion Cancer Center

San Francisco, California, United States

UCLA Parkside Cancer Center

Santa Monica, California, United States

University of Colorado

Aurora, Colorado, United States

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, United States

Florida Cancer Specialists - Sarasota - SCRI

Sarasota, Florida, United States

Indiana University

Indianapolis, Indiana, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Case Western Reserve University

Cleveland, Ohio, United States

The University of Oklahoma

Norman, Oklahoma, United States

Oregon Health and Science University

Portland, Oregon, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Mary Crowley Cancer Center

Dallas, Texas, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Start South Texas Accelerated Research Therapeutic

San Antonio, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 38809056 (View on PubMed)

Other Identifiers

PY159-2-01

Identifier Type: -

Identifier Source: org_study_id